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Endocrine practice ?'s

Terms in this set (305)

GH deficiency
Growth hormone (GH) deficiency is defined as a decreased growth velocity, delay in skeletal maturation, absence of other explanations for poor growth (lack of intake), and laboratory tests demonstrating decreased GH secretion. Etiology of GH deficiency can be congenital, genetic, acquired, or idiopathic, which is the most common. Infants usually have a normal birth weight and may have a slightly decreased length. In addition, most infants present with other endocrine deficiencies like hypoglycemia, hypothyroidism, and/or adrenal insufficiency. Children may present with truncal adiposity because growth hormone promotes lipolysis. Serum GH or intrinsic growth factor levels may or may not be decreased. In patients who do not have a demonstrated decrease in these hormones, a trial period with GH is indicated. These patients and positive GH-deficient patients receive a once-daily subcutaneous injection of recombinant human GH. Congenital hypothyroidism typically presents with short stature (typically noted after the 4-month newborn visit), delayed epiphyseal development, delayed closure of fontanelles, and retarded dental eruption in addition to other signs of hypothyroidism. Cushing disease typically presents with truncal adiposity with thin extremities, muscle wasting, decreased growth rate, and moon facies. Laboratory results show elevated adrenocorticosteroids both in urine and serum, hypokalemia, eosinopenia, and lymphocytopenia. Typically, in patients younger than the age of 12, Cushing disease is secondary to administration of ACTH or glucocorticoids. Congenital adrenal hyperplasia typically presents with pseudohermaphroditism in females or salt-losing crisis in males with or without isosexual precocity. There is an increased linear growth and advanced skeletal maturation.
Collecting ducts
Explanation
Collecting dust is the correct response.

A known side effect of lithium is nephrogenic diabetes insipidus. This side effect is experienced by a significant minority of the patients taking lithium. Nephrogenic diabetes insipidus results when the collecting duct of the kidney does not respond to the antidiuretic hormone (ADH).

The posterior lobe of the pituitary is the neurohypophysis. The neurohypophysis secretes antidiuretic hormone (ADH) and oxytocin. The production of the posterior pituitary hormones actually occurs in the hypothalamus.

The anterior lobe of the pituitary is the adenohypophysis. The anterior lobe of the pituitary secretes follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, growth hormone (GH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) (and the corticotropin related peptides).

The collecting duct is a portion of the nephron. It is also called the collecting tubules. Urine enters the collecting duct from the distal convoluted tubule. The collecting duct is responsive to ADH.

The glomerulus is a specialized capillary tuft. The endothelium of the glomerulus is fenestrated. The glomerulus is surrounded by Bowman's capsule. A renal corpuscle consists of the glomerulus and Bowman's capsule. A renal corpuscle is sometimes called a Malpighian corpuscle. Renal corpuscles are seen in the kidney cortex.

The loop of Henle is part of the nephron. It is shaped like a hairpin. The proximal convoluted tubule leads into the descending limb of the loop of Henle. The ascending limb of the loop of Henle goes to the distal convoluted tubule.
TSH
Explanation
Graves' disease is a type of hyperthyroidism caused by a generalized over-activity of the entire thyroid gland. The patient appears hot and flushed, and the thyroid gland enlarges in this condition. It is believed that Graves' disease is an autoimmune disorder. Antibodies are produced against certain proteins on the surface of thyroid cells, stimulating those cells to overproduce thyroid hormones. In this condition antibodies are produced against the thyrotropin receptor, thyroglobulin, thyroid peroxidase, and sodium-iodide symporter. The circulating autoantibodies continuously stimulate the thyroid gland via the thyrotropin receptor. Associated suppression of the pituitary thyrotropin level is due to increased production of thyroid hormones. The onset of the disease is gradual, and the symptoms may be mistaken for nervousness due to a stressful life situation. Weight loss occurs, and it is followed by other symptoms, such as trembling, muscle weakness of the upper arms and thighs, and insomnia. The pituitary gland releases Thyroid Stimulating Hormone (TSH) in response to insufficient levels of thyroid hormone. Communication between the pituitary gland and the thyroid gland through TSH levels controls the levels of thyroid hormone in the blood. If the levels of thyroid hormone are low, then the levels of TSH will rise. The measurement of TSH in the blood is taken as a measure of thyroid function. In Graves' disease, there is a suppressed level of thyrotropin along with elevated levels of free T4 or T3 hormone levels. The new generation (III generation) assay of TSH is very sensitive and has revolutionized diagnosis of Graves' disease by providing accurate measurements of very low TSH levels. Suppression of TSH is an early and highly sensitive marker of thyrotoxicosis. Estimation of thyroid peroxidase, protein-bound iodine, thyroglobulin, and thyrotropin-releasing hormone are not as reliable as TSH assay.
Hypoglycemia
Explanation
Hypoglycemia, reduced blood glucose level below the laboratory reference ranges, is most likely to present with a toxic-metabolic state emulating an acute agitation and/or an acute psychosis; this patient demonstrates these symptoms. Given the known history of diabetes, and even in the absence of a history of a insulin-dependent diabetes disorder, the health care provider should check the patient's blood glucose level; if found to be low, glucose should be administered intravenously.

Hyponatremia, which is reduced serum sodium below the laboratory references ranges, may present with seizures; however, none are evident in this case. Hypokalemia, which is reduced serum potassium below the laboratory reference ranges, may present with muscular weakness; however, that is not a listed symptom. Hypocalcemia, which is reduced serum calcium below the laboratory reference ranges, may present with neuromuscular hyperirritability; it is not mentioned in this case. Hypovolemia, which is reduced circulating volume, may present with cardiovascular collapse verging on shock. This patient is not in such a condition. Hypomagnesemia, which commonly results from poor nutrition, would be unlikely in this setting. Hypothermia, which is reduced body temperature, may present with slow mentation; it is not a condition pertinent to this case.

The core ethical and legal principle is to be reasonably certain that all efforts have been provided. Afterwards, it is important to identify, diagnose, treat, and correct all acute medical issues and crises before simply providing injections of intra-muscular, anti-agitation, and/or anti-psychotic medications that necessarily carry an element of risk and are of no benefit in this setting.
Cardiovascular Disease
Explanation
This patient is presenting with acromegaly, a rare disorder of excess growth hormone (GH), most often caused by a GH-secreting pituitary adenoma. Because the changes are insidious, patients may take years to present with symptoms and be diagnosed. The patient and close family members may not notice the acral skeletal growth enlargement, unless it affects the fit of shoes, rings and/or hats. Other possible signs and symptoms of acromegaly include fatigue, headaches, visual field deficits, hypertension, coarse facial features, carpal tunnel syndrome, and joint pain. Treatment may include surgical resection of the adenoma, medications or radiation. Patients with acromegaly are at risk for early death; the primary cause of death is cardiovascular disease. Patients with acromegaly may develop hypertension, cardiomyopathy, and hypertrophy.

Hypogammaglobulinemia is an immune disorder in which the affected patient has reduced levels of immunoglobulins and is at risk for infection. Hypogammaglobulinemia, and other immune system disorders, are not identified as acromegaly complications.

Multiple myeloma is a plasma cell cancer that affects bone marrow. While acromegaly does affect bone growth, it has not been linked with bone malignancy.

Osteoporosis is the demineralization of bone structure, leading to bone weakness and fracture. It is not considered a complication of acromegaly.

Parkinson disease is a chronic, progressive neurologic disorder associated with tremor, rigidity, abnormal gait, and mental changes, such as dementia and depression. Patients with acromegaly are not known to be at a higher risk of Parkinson disease.
Explanation
'Headache, palpitations, and diaphoresis' is the correct answer. These 3 symptoms together make up the "classic triad" in patients with a pheochromocytoma. A pheochromocytoma is a catecholamine-producing tumor that is most commonly found in the adrenal gland superior to the kidney. It is commonly diagnosed due to hypertension, but it causes less than 1% of the cases of hypertension. The symptom triad listed above has been found to have a specificity of almost 94% and a sensitivity of almost 91% for patients with pheochromocytomas. Patients may also experience other symptoms, including constipation, weight loss, flushing, and dizziness. Since the tumor produces catecholamines, excess production is usually measured by determining the levels of excreted metabolites during a 24-hour period by a 24-hour urine. Abdominal MRI can then be used to confirm the presence of the adrenal tumor.

'Dry skin, fatigue, and shortness of breath' is not the correct answer. Fatigue is not a common symptom in patients with a pheochromocytoma, but it could certainly occur secondary to the pain, anxiety, or shortness of breath. Dry skin is actually the opposite of the common symptom, diaphoresis, which tends to occur in patients with a pheochromocytoma. Shortness of breath is a symptom that patients with pheochromocytoma can experience, but it is not part of the classic triad of symptoms.

'Fatigue, flushing, and constipation' is not the correct answer. Fatigue is not a common symptom in patients with a pheochromocytoma, but it could certainly occur secondary to the pain, anxiety, or shortness of breath. Flushing and constipation can both occur in patients with a pheochromocytoma, but these symptoms are not part of the classic triad, nor do they have the high sensitivity and specificity of the classic triad of palpitations, diaphoresis, and headache.

'Headache, dry skin, and nausea' is not the correct answer. Headache is 1 of the symptoms associated with the classic triad of symptoms that patients with a pheochromocytoma can experience, but dry skin is certainly not a symptom of a pheochromocytoma. The opposite is true, actually, as patients tend to experience diaphoresis. Nausea can occur, but it is not common and is not a part of the classic triad of symptoms.

'Flushing, constipation, and nausea' is not the correct answer. All 3 of these symptoms can occur in a patient with a pheochromocytoma, but none of them are a part of the classic triad of diaphoresis, headache, and palpitations that has a high specificity and sensitivity for pheochromocytoma.
Desmopressin
Explanation
This patient has subjective and objective findings consistent with diabetes insipidus. Diabetes insipidus is characterized by the decreased production or action of antidiuretic hormone (ADH), which is produced by the posterior pituitary. The body is then unable to concentrate the urine, resulting in polyuria, nocturia, elevated serum osmolality, and decreased urine specific gravity. The treatment of choice for this patient's diabetes insipidus is desmopressin, which is a potent antidiuretic.

Bromocriptine is an FDA-approved dopamine-agonist used in the treatment of hyperprolactinemia. Other uses include the treatment of acromegaly and Parkinson's disease. The mechanism of action for bromocriptine includes stimulation of dopamine receptors and inhibition of anterior pituitary prolactin secretion. It has no direct action on the posterior pituitary's secretion of ADH, nor on the kidney's urine-concentrating ability.

Because autoimmune destruction of the pituitary is theorized as a cause in idiopathic central diabetes insipidus, there are often deficiencies in growth hormone (GH), thyroid stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH), as well as the deficiency in antidiuretic hormone (ADH). Growth hormone (GH) would be helpful in treating disorders affecting the anterior pituitary's secretion of GH; however, treating this patient with growth hormone will not directly address the polyuria and nocturia caused by his diabetes insipidus. The presentation of a GH deficiency would include short stature, growth failure, hypoglycemia in infancy, and central distribution of body fat. This patient did not have a presentation consistent with GH deficiency.

In cases of panhypopituitarism, secretion decreases for all pituitary hormones including ADH and ACTH. In this case, the low ACTH levels would lead to low cortisol levels and necessitate treatment with hydrocortisone. Hydrocortisone would not appropriately address this patient's polyuria and nocturia from his diabetes insipidus.

Spironolactone, a potassium-sparing diuretic, inhibits the effects of aldosterone on the renal tubules. Using a diuretic on this patient would only exacerbate the fluid loss and polyuria.
Suprapubic distension
Explanation
This patient's presentation and past medical history are suggestive of central diabetes insipidus. Decreased secretion or action of antidiuretic hormone usually manifests as diabetes insipidus, a syndrome characterized by the production of abnormally large volumes of dilute urine. The 24-hour urine volume is >50 mL/kg body weight, and the osmolarity is <300 mosmol/L. The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. It also results in a slight rise in plasma osmolarity that stimulates thirst and a commensurate increase in fluid intake (polydipsia). Overt clinical signs of dehydration are uncommon unless fluid intake is impaired.

The physical examination findings vary with the severity and chronicity of DI. The examination findings may be entirely normal. Hydronephrosis, with pelvic fullness, bladder enlargement, flank pain or tenderness, or pain radiating to the testicle or genital area may be present. Unless the thirst mechanism is impaired or access to fluid is restricted, dehydration is not seen. Aside from an enlarged bladder, no specific signs of diabetes insipidus exist.

Hypotension, not hypertension, would be anticipated with significant and chronic dehydration. Adnexal masses and cervical motion tenderness reflect underlying gynecological illnesses not present in this patient. Diminished vibratory sensation suggests peripheral neuropathy, which is not a known manifestation of diabetes insipidus.
Begin rosuvastatin 10 mg every day
Explanation
This patient should be prescribed a statin. The statin (HMG-CoA reductase inhibitor) class of drugs has revolutionized the treatment of hypercholesterolemia, as they are highly efficacious and very well tolerated.

The LDL-C goal for patients with coronary heart disease (CHD) equivalent risk, including patients with diabetes mellitus, should also be less than 100 mg/dL. In patients considered to be very high risk, a goal of less than 70 mg/dL is an acceptable option.

Patients with CHD or CHD equivalent are prescribed drug therapy simultaneously with therapeutic lifestyle changes if their LDL-C concentration is greater than or equal to 130 mg/dL. Drug therapy is optional for patients whose LDL-C value is 100-129mg/dL. For rosuvastatin at 5-40mg/d, the LDL-C level is lowered by 45 - 63%.

Dietary cholesterol should be limited to less than 200mg/day. Other dietary changes, such as increased soluble fiber found in oat bran or psyllium, may reduce LDL cholesterol by 5-10%. Diets rich in antioxidant vitamins found in fruits and vegetables may be helpful in the reduction of oxidation of LDL, thereby reducing atherogenesis.

All patients whose risk from CHD is considered high enough to warrant pharmacologic therapy of an elevated LDL cholesterol should be given aspirin prophylaxis at a dose of 81mg/day unless contraindicated.

Cholestyramine is a bile acid sequestrants used primarily as additional therapy in patients with familial hypercholesterolemia who experience inadequate LDL-C lowering with statins.
DM
Explanation
Your patient has a serious systemic infection, most probably pyelonephritis in the settings of poorly regulated diabetes mellitus. In diabetes, infections may precipitate metabolic disturbances, but metabolic disturbances may also facilitate the infection. Metabolic disturbances (hyperglycemia, acid-basic dysregulations) impair humoral immunity and the function of polymorphonuclear leukocytes and lymphocytes. Not only diabetes, but other chronic diseases, increase the risk of acquiring systemic infections. The strongest connection was found in chronic lung disease and chronic kidney disease. Long-standing diabetes may also lead to chronic kidney disease, which could be an additional risk factor in this patient.

Although polyuria with urinary frequency and urgency may be caused by diabetes insipidus, it is much more frequently caused by uncontrolled diabetes mellitus. Another reason that your patient may have polyuria is diuretic therapy.

Diuretic therapy may contribute to polyuria, but it does not contribute to the development of systemic infection.

Patients with mild cognitive impairment can forget to take their medications from time to time, thus contributing to poor regulation of their diseases, but mild cognitive impairment is not a risk factor for systemic infection.

Vaccines recommended in seniors (over 65) are: influenza, herpes zoster, diphtheria/tetanus, pertussis, and pneumococcal. Not getting immunized because of the fear of a needle will put your patient at risk for developing those diseases. However, she was not exposed to any of those diseases and has no signs and symptoms of any of them.
Explanation
This patient will most likely have a 'rugger Jersey' appearance to her vertebrae if she has a back or skeletal X-ray.

She has hyperparathyroidism. End stage kidney disease patients (stage 5 chronic kidney disease) should have PTH levels between 150 and 300 pg/ml. She is likely hyperphosphatemic because of impaired renal phosphorus excretion, inadequate dialysis, and failure to take phosphorus binders when she eats.

Hyperphosphatemia stimulates PTH release. Vitamin D (i.e., paricalcitol) can suppress PTH release, but she may be missing adequate doses when she skips her dialysis sessions.

Excess PTH leads to abnormal bone remodeling, including excessive resorption. Lucencies may be seen in poorly mineralized areas. 'Pepper pot skull' refers to such scattered lucent findings on skull films; 'cinnamon skull' is not a term used to describe the radiologic findings of hyperparathyroidism.

'Pseudofractures' are the straight lucent bands of poorly mineralized bone seen in hyperparathyroidism, particularly in long bones. Quasifractures are not radiologic findings seen in hyperparathyroidism.

DEXA (Dual X-ray absorptiometry) scans are quantitative measures of bone mineralization. Low bone mineralization is inversely related to PTH levels (Brenner). This patient will not likely have a normal DEXA scan because her bones are diseased. DEXA is not a diagnostic test for renal bone disease; measures of PTH, together with calcium, phosphorus, and alkaline phosphatase levels, are better diagnostic tests for renal bone disease.

Thumbprinting refers to bowel wall edema noted on CT or abdominal radiographs in certain conditions, such as mesenteric ischemia (Harrison's ch. 279) and toxic megacolon. Ischemia often requires surgical intervention. Toxic megacolon is treated surgically and with antibiotics.
Metformin is the only hypoglycemic agent that has been shown to reduce mortality rates in patients with type II diabetes. Insulin resistance, decreased insulin secretion, and increased hepatic glucose output are the hallmarks of type II diabetes. Metformin decreases hepatic glucose output and, to a lesser extent, sensitizes peripheral tissues to insulin. Metformin can reduce A1C levels by an average of 1 - 2.5%. Metformin has also been shown to slow progression of impaired glucose tolerance to diabetes. Metformin causes weight loss and is not associated with hypoglycemia. Gastrointestinal symptoms associated with metformin can be minimized by starting at a low dose and titrating slowly. It is usually administered 2 times a day. Long-acting preparations that are administered once daily are also available. Metformin rarely causes lactic acidosis, and current guidelines recommend against using metformin when creatinine levels are ≥1.4 in women and ≥1.5 in men. Metformin is approved for use in children over 10 years.

Glipizide is a sulfonylurea insulin secretagogue, and it has not been shown to have any effect on cardiovascular morbidity or mortality. Severe hypoglycemia can occur with glipizide.

Actos causes fluid retention and weight gain. It increases the incidence of heart failure, but it has not been shown to affect cardiovascular mortality.

Insulin is typically introduced when glucose control is no longer possible with oral agents, or when contraindications to oral agents exist. Newly diagnosed patients may also benefit from short-term insulin use if sugars are extremely high. Such patients would typically have A1C levels greater than 9%.

Acarbose is an alpha-glucosidase inhibitor and has been shown to reduce cardiovascular events; average A1C reduction is only 0.5 - 1%. It has to be taken 3 times a day with meals; gastrointestinal side effects can be troubling.
Genetic testing for possible familial cancer syndrome
Explanation
The vignette suggests a possible familial cancer syndrome. MEN 2a syndrome fits the picture of 2 generations and multiple members of the family affected. MEN 2a is an autosomal dominant disease, characterized by primary hyperparathyroidism, medullary carcinoma of thyroid, and pheochromocytoma. The father has features suggestive of pheochromocytoma, one of the causes of early onset hypertension and sudden cardiac death. The older brother has an adrenal mass that was excised, indicating a possible pheochromocytoma, and a malignant neck mass, indicating possible medullary cancer of the thyroid.

MEN 2a is most commonly caused by mutations in the RET proto oncogene. The mutations are more commonly familial, although they may occur spontaneously. Genetic analysis for the mutation is done as a screening test in particularly high risk families, and a prophylactic thyroidectomy may be advocated. Mutation testing has replaced the regular measurement of serum calcitonin as a screening test.

Other tests that may be done include:

Serum Ca, parathyroid hormone, and plasma free metanephrine or urinary catecholamine levels
Pheochromocytoma localization with MRI or CT
A routine colonoscopy is incorrect. The US Preventive Services Taskforce recommends a routine colonoscopy starting at age 50 and repeated every 10 years. With a family history of colonic malignancy, the guidelines suggest earlier screening. However, this patient has no family history of colon cancer and is only 34 years of age.

Thyroid function testing is incorrect. There is no indication at the present time for a thyroid function testing. Calcitionin may be measured to screen for early medullary cancer, but the thyroid hormones themselves are of no benefit.

Reassurance is incorrect. With such a strong family history, reassuring the patient and sending him home would not be appropriate.

Renal ultrasound to look for cysts is incorrect. It may be recommended if suspecting polycystic kidney disease, but there is no history suggestive PKD.
Explanation
The patient would be diagnosed with hypercholesterolemia with high risk for Coronary Heart Disease (CHD) for several reasons. His total cholesterol is considered elevated, as it is more than 200mg/dL, and his Low-Density Lipoprotein Cholesterol (LDL) is also elevated, as it is more than 160mg/dL. In addition, his High-Density Lipoprotein Cholesterol (HDL) is less than 35mg/dL, which increases his risk for CHD.

In order to be diagnosed with hypercholesterolemia with low risk for CHD, the patient would essentially have to have total cholesterol and LDL levels that are elevated, but not to the extent that his are. In particular, an LDL level above 100mg/dL, but still under 160mg/dL, is considered high, but does not have the same risk as a level that is over 160mg/dL, as his is. In addition, he could have lower risk for CHD had his HDL level been over 60mg/dL.

The patient would not be diagnosed with hypertriglyceridemia, with or without risk for CHD, because his triglycerides are actually within normal limits. Triglyceride levels under 200mg/dL are considered desirable. Levels between 200 and 400mg/dL are considered borderline elevated, and levels over 400mg/dL are considered high.

The patient would definitely not be diagnosed with a normal cholesterol profile. A normal cholesterol profile would include a total cholesterol under 200mg/dL, an HDL level over 60mg/dL, an LDL level under 130mg/dL, and a triglyceride level under 200mg/dL. Of the 4 serum levels, he only has a normal triglyceride level. The rest are abnormal and thus increase his risk for CHD.
Perform a rapid ACTH stimulation test
Explanation
This patient's most likely diagnosis is primary adrenal insufficiency, known as Addison's disease.

The diagnosis of adrenocortical insufficiency rests on the assessment of the functional capacity of the adrenal cortex to synthesize cortisol. This is accomplished primarily by use of the rapid ACTH stimulation test (cortrosyn, cosyntropin, or synacthen).

Imaging of the brain is unnecessary for this patient at this time since Addison's disease is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed. This patient's hyperpigmentation signifies adrenal insufficiency, since hyperpigmentation only occurs with primary adrenal insufficiency (not secondary corticosteroid insufficiency, i.e., Hypothalamic-Pituitary-Adrenal Axis (HPA) Dysfunction). It is caused by the stimulant effect of excess adrenocorticotrophic hormone (ACTH) on the melanocytes to produce melanin. The hyperpigmentation is caused by high levels of circulating ACTH that bind to the melanocortin 1 receptor on the surface of dermal melanocytes.

A low salt diet and increased potassium intake is inappropriate for this patient since most patients with Addison's disease have hyponatremia and hyperkalemia.

Antibiotics are not indicated at this time, as this patient does not have an infectious pathology.

Metyrapone (metopirone) is an inhibitor of endogenous adrenal corticosteroid synthesis. It inhibits the 11-B-hydroxylation reaction in the adrenal cortex and is thus utilized as an agent that inhibits steroidogenesis in Cushing syndrome.
Lipoprotein lipase deficiency
Lipoprotein lipase deficiency is characterized by a defect in the degradation of chylomicrons. Lipoprotein lipase is required for the catabolism of triacylglycerol present in chylomicron to free fatty acids and glycerol. Lipoprotein lipase is present in the endothelium of blood vessels of the adipose tissue and muscle. A high serum triglyceride level characterizes this disorder. The serum triglyceride level is usually >1500mg/dl. The serum cholesterol is marginally raised. Lipoprotein lipase may be released from the tissues by administration of intravenous heparin. Diagnosis is confirmed by measuring lipoprotein lipase using specific immunologic techniques. Serum triglycerides levels are markedly elevated (>1500mg/dl). The most frequent presentation is as recurrent abdominal pain accompanied by hepatosplenomegaly. In many cases, patients present with acute pancreatitis. Observation of plasma, after keeping it overnight at 4 C, shows the presence of a creamy layer on the plasma. Management involves the administration of medium-chain triglycerides in the diet that enter the portal circulation directly without formation of chylomicrons.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic defect in which there is deficiency of functional LDL receptors. These LDL receptors recognize the Apo B100 present in IDL and LDL. LDL/IDL binds to the receptor and is taken up into the cell by receptor-mediated endocytosis. In FH, there is decreased peripheral uptake of LDL and IDL, which causes a marked increase in the serum cholesterol level. Serum triglycerides are within normal limits. There is a large accumulation of cholesterol in the macrophages of the tendons that causes xanthomas, indicating that the scavenger cells are taking up and degrading large amounts of LDL. Patients manifest with an increased risk of atherosclerosis and coronary artery disease at an early age. There is cholesterol accumulation in the arteries, especially at the root of the aorta, causing aortic stenosis.

Apo C II is the apolipoprotein present in chylomicrons that is required for the activation of lipoprotein lipase. Absence of Apo CII is inherited as a recessive disorder. It is characterized by high levels of chylomicrons and serum triglycerides. It is distinguished from lipoprotein lipase deficiency by the assay of lipoprotein lipase after the administration of intravenous heparin. In this disorder, lipoprotein lipase levels are normal; however, Apo CII levels are low. Symptoms of presentation and management of the condition are similar to lipoprotein lipase deficiency.

Familial combined hyperlipidemia (Frederick son's type IIB hyperlipoproteinemia) is characterized by an increase in LDL and VLDL. In these patients, there is an increased fasting serum cholesterol and serum triglycerides level. There is an increased risk of coronary artery disease in these patients. Serum cholesterol level is usually in the range of 200-300 mg/dl and serum triglyceride is in the range of 200-500mg/dl.

Abetalipoproteinemia is characterized by an absence of lipoprotein species containing apoprotein B, which are LDL, chylomicrons, and VLDL. The levels of triglycerides and total cholesterol are very low (<50mg/dl). The predominant features include malabsorption of dietary fat and steatorrhea. There is also malabsorption of the fat-soluble vitamins. Lack of vitamin E causes progressive degeneration of the CNS, which manifests as neurological abnormalities by the first decade. There is decreased visual acuity and night blindness as a result of vitamin A deficiency.

Familial type III hyperlipoproteinemia (dysbetalipoproteinemia) is characterized by increased levels of IDL in circulation. There is also an increase in the chylomicron remnant particles. There is a defect in apolipoprotein E, which is required for the uptake of chylomicron remnants and IDL by the liver. In these individuals, the fasting serum cholesterol and triglycerides are raised. Patients present with an increased risk of premature atherosclerosis and palmar xanthomas.
The correct response is papillary.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer in the United States; it has a prevalence rate of 80 - 90% of all thyroid cancers. It arises from the follicular epithelial cells of the thyroid, as does follicular thyroid cancer (FTC), which is the 2nd most frequently occurring thyroid cancer (accounting for 5 - 15% of all cases). Together, they are defined as well-differentiated thyroid carcinomas; when identified early they have a good, and frequently curable, prognosis. Psammoma bodies (PBs) are concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC)

Hürthle cell carcinoma (oncocytic) is a variant of FTC.

Also arising from the follicular epithelial cells is undifferentiated (anaplastic) thyroid carcinoma; this accounts for < 5% of thyroid cancers and carries a worse prognosis than the well-differentiated histologic forms. It is aggressive and often refractory to treatment.

Medullary thyroid cancer (MTC) arises from the parafollicular cells (C cells), which are calcitonin-producing and account for 5 - 10% of thyroid carcinomas. 75% of MTC patients will have sporadic cases, whereas 25% will have hereditary forms such as multiple endocrine neoplasia 2A (MEN 2A), MEN 2B, or familial (FMTC). MEN 2A is associated with hyperparathyroidism, a high risk of MTC, and pheochromocytoma. MEN 2B is associated with MTC, an increased risk of pheochromocytoma, and mucosal neuromas on the lips, tongue, and GI tract.
Hypoglycemia
Explanation
Hypoglycemia results from low blood glucose. The symptoms of hypoglycemia can vary depending on the glucose level. It also varies from person to person. Symptoms can include weakness, pallor, hunger, palpitations, sweating, nervousness, and trembling. These symptoms usually resolve when the glucose levels return to normal. Anyone who has experienced an episode of hypoglycemia describes a sense of urgency to eat and resolve the symptoms. The symptoms are usually easily recognized by patients. If the patient does not eat or take an agent to increase their blood glucose level, the brain will eventually begin to suffer. The patient can develop drowsiness, confusion, behavioral changes, seizures, and coma.

Causes of hypoglycemia include insulin resistance in patients who are pre-diabetic, insulin producing tumors, and medications. True hypoglycemia is found in patients with diabetes. Patients who are pre-diabetic may have low blood glucose if they are fasting and their insulin level is high.

Diagnosis is usually made through history and physical and is confirmed with laboratory measurements. Plasma insulin, plasma C-peptide, and serum glucose should be checked.

Treatment consists of recognizing the symptoms and resolving the hypoglycemia. The patient's symptoms can usually be resolved with food and drink containing sugar. If the patient does not improve after consumption of sugar, he or she should seek medical care for further evaluation.

The other choices are incorrect since the symptoms and laboratory results do not match. The patient's labs are normal with the exception of low hemoglobin and blood glucose levels.

Transient ischemic attack is an acute episode stroke that last usually less than 24 hours. It can be thought of as a stroke in which the symptoms resolve. It is caused by a temporary occlusion of a blood vessel. Symptoms are not affected by food or drink.

Anxiety disorders can result in excessive worry and the feeling of being overwhelmed. Lab results, such as blood glucose levels, would not be affected.

Sepsis results from a bacterial infection that has spread to the blood. Patients may have fever, chills, tachycardia, decreased urination, confusion, dizziness, and an elevated white cell count. This patient's white blood cell count was normal.

Depending on the type of seizure, seizure disorders can produce disorientation, uncontrollable movements, or staring into space. Unlike symptoms of hypoglycemia, they do not end when the diet is changed.
A 62-year-old woman presents to her OB/GYN clinic for an annual exam. She reports that she has not felt well for several months, but her family practice physician retired, and she kept hoping her symptoms would improve. She reports stretch marks and a weight gain of about 20 pounds, especially noticeable in her face. She feels fatigued and has no sex drive; she also feels more irritable. She notes increased dark hairs growing on her chin. The patient reports easy bruising, but denies blood in the stools. She denies fever, chills, foreign travel, a change of sex partner, and suicidal thoughts.

Her past medical history is significant for asthma, with periodic hospitalizations for asthma attacks. She achieved menopause at the age of 51 years. She has not had any surgeries. She takes prednisone 40 mg daily, an inhaler with fluticasone propionate/salmeterol 2 times daily, and an albuterol inhaler as needed for her asthma. She has no allergies. She is retired and lives at home with her husband; she denies use of tobacco, alcohol and street drugs.

BP is 162/92 mm Hg, and pulse is 98. Respiratory rate is 12. Weight is 170 lbs, and height is 63", making her BMI 30.11.

On physical exam, the patient has a rounded, full face; she appears fatigued, but she is pleasant and cooperative. Striae are noted on her abdomen, and hirsutism is present on her chin and abdomen. There appears to be a large fat deposit on the upper back. Her abdomen is obese, with some muscle wasting on the patient's extremities. The remainder of her exam is normal.



Question
What prescription intervention is the most appropriate for this patient's condition?

Answer Choices
1 Discontinue inhaled fluticasone propionate/salmeterol
2 Discontinue prednisone
3 Initiate beta-blocker (e.g., metoprolol)
4 Initiate combination hormone therapy (e.g., estradiol/norethindrone acetate)
5 Initiate stimulant for weight loss (e.g., phentermine hydrochloride)
Explanation
This patient is presenting with Cushing syndrome, an excess of glucocorticoids; it is most likely iatrogenic, caused by her daily prednisone. The most appropriate prescription intervention for her condition is to discontinue the prednisone. This common steroid is often given for acute flares of chronic diseases. However, chronic daily use can lead to a glucocorticoid excess known as Cushing syndrome. Cushing syndrome is characterized by central obesity, muscle wasting, hirsutism, a 'buffalo hump' on the upper back, 'moon facies', weight gain, hypertension, decreased libido, irritability, and several other possible signs/symptoms. Unrecognized and untreated Cushing syndrome can lead to osteoporosis. Tapering off the prednisone (rather than immediate discontinuation) helps prevent sudden adrenocortical insufficiency.

This patient's inhaled fluticasone propionate is also a steroid medication; it is given to reduce inflammation in the airways. (The salmeterol is a long-acting beta-agonist.) This patient has no current respiratory signs or symptoms, so we can assume her asthma is currently controlled. Typically, the inhaled and intranasal steroids are considered low enough strength that they will not lead to corticosteroid excess and Cushing syndrome. The systemic steroid, prednisone, is much more potent, so it is the likely culprit for this patient's symptoms. It would be inappropriate to discontinue her inhaled fluticasone propionate/salmeterol, unless an alternate asthma treatment is started; changing the inhaled asthma medication would not alter her Cushing syndrome symptoms.

This patient's blood pressure is elevated, but not at urgently high levels. Cushing syndrome is associated with hypertension. It would be wise to discontinue the prednisone and monitor this patient's blood pressure. With resolution of her Cushing syndrome (and anticipated weight loss), the elevated blood pressure may normalize. If her blood pressure remains elevated, it would not be advisable to initiate a beta-blocker (e.g., metoprolol) due to the common side effect of fatigue; this patient already complains of fatigue.

This patient's current condition cannot be attributed to normal menopausal changes. Normal post-menopausal changes include vasomotor symptoms (such as hot flashes and night sweats) and vulvovaginal changes (such as atrophy, vaginal dryness and dyspareunia). Some women may experience some mild weight gain and irritability, but this patient's other symptoms are not related to drops in sex hormones. It may be acceptable to initiate combination hormone therapy (e.g., estradiol/norethindrone acetate) for women with acute menopausal symptoms, but it would not be appropriate in this patient's case.

This patient's concerns should not be attributed to a weight-gain only issue. Weight gain is a common side effect from exogenous corticosteroids and should reverse with discontinuation of the medication. A dietician referral could be offered in addition to treatment of this patient's Cushing syndrome. It would be inappropriate to initiate a stimulant for weight loss (e.g., phentermine hydrochloride), especially with elevated blood pressure/hypertension.
The correct answer is the combination of fatigue, dizziness, and salt craving with increased pigmentation of her lips and hand creases, as well as hair loss. Addison's disease is the result of adrenal cortex destruction, which causes deficiencies in cortisol, aldosterone, and androgens. Patients can have any combination of various systemic symptoms, including fatigue, weakness, nausea, vomiting, abdominal pain, dizziness, chronic diarrhea, depression, salt craving, and a decreased tolerance for cold. In addition, the physical examination findings can also vary. Some possible findings are hypotension, weight loss, vitiligo, hair loss, and increased pigmentation. The increased pigmentation can occur in the hand creases, dental-gingival margins, buccal and vaginal mucosa, lips, areolas, scars, and pressure points. The increased pigmentation is a result of increased secretion of β-lipoprotein.

The combination of weight gain, decreased libido, and menstrual irregularity with moon facies and increased adipose tissue in neck are indicative of a patient with Cushing's disease. Cushing's disease is essentially the opposite of Addison's disease; its signs and symptoms are caused by an excess of adrenocorticotropin rather than the deficiency seen in Addison's disease. Patients with Cushing's disease can also experience hypertension, hirsutism, depression, easy bruising, muscle weakness, obesity, thin skin, skeletal growth retardation, and acne.

The combination of cramping, numbness around mouth, and tingling in distal extremities with carpopedal spasm and exaggerated deep tendon reflexes could occur in a patient with hypoparathyroidism. This disorder is a result of a deficiency of parathyroid hormone from congenital absence, injury, surgery, or other diseases. Most of the symptoms associated with hypoparathyroidism are a result of hypocalcemia.

The combination of bone pain, flank pain, and anxiety with hypertension and mental confusion could occur in a patient who has hyperparathyroidism. This disorder is characterized as dysfunction in the body's regulatory system for parathyroid hormone. While up to 75% of patients can be asymptomatic, the hypercalcemia associated with hyperparathyroidism can result in the classic complaints of painful bones, renal stones (causing flank pain), abdominal groans, and psychic moans.

The combination of hair loss, decreased energy, and constipation with periorbital puffiness and dry, coarse skin is indicative of hypothyroidism. Hypothyroidism is typically an autoimmune disease or a result of prior radiation therapy or thyroid surgery.
TSH, T4, ESR
Explanation
This patient has a viral infection followed by infection of the thyroid gland, causing subacute thyroiditis, which is also known as de Quervain's syndrome. Neck pain and a tender mass in the neck anteriorly indicate thyroid inflammation. Sometimes, the swollen thyroid may cause obstructive symptoms. Sudden release of thyroid hormone may cause transient hyperthyroidism; this is the case in this patient who is experiencing nervousness, tremors, palpitations, and sweating. Lab tests show low TSH, high free T4, high ESR, high C reactive protein, and raised serum thyroglobulin. Treatment is symptomatic; anti-inflammatory medication, steroids, and beta-blockers should be given for hyperthyroid symptoms. A reasonable approach is to relieve the pain with high doses of a non-steroidal, such as aspirin or naproxen. If the symptoms are not relieved in 2 - 3 days, prednisone at 30 - 40 mg daily should be given in the absence of contraindications. The usual treatment can last for 4 - 8 weeks. Once the pain is controlled, prednisone should be tapered. If the patient has severe pain, a steroid can be started right away. In the absence of relief from these 2 modes of treatment, the diagnosis should be questioned. Symptoms from release of thyroid hormones need not be treated if they are mild; however, if they are more severe, propranolol or atenolol help in symptomatic relief from anxiety, tremors, and palpitations. The differential diagnosis of this case includes group A beta hemolytic streptococcal infection, infectious mononucleosis, cervical lymphadenitis, and occasionally scrofula. In streptococcal infections of the throat, tonsils are enlarged, exudates are seen, and cervical lymphadenopathy is obvious. Infectious mononucleosis is also characterized by high fever, pharyngitis, and lymphadenopathy, especially posterior cervical, with hepatosplenomegaly in many cases. Fatigue is prominent without tremors, anxiety, or palpitations. The heterophile antibody test is positive, with atypical lymphocytes in the peripheral smear. Scrofula is a tuberculous lymphadenitis caused by mycobacterium scrofulaceum. It is characterized by single gradually enlarging mass in neck on 1 side; the mass is non-tender, rarely indurated, erythematous, or with a draining sinus. Cervical lymphadenitis has multiple etiologies and can be caused by viral, bacterial, fungal, or (rarely) mycobacterial organisms. Multiple lymph nodes are usually palpable, and they may be tender. The underlying condition is usually obvious.
autoimmunity
Explanation
This patient has a clinical picture that suggests hypothyroidism, which is confirmed by the low levels of free T4 and elevated TSH. A family history of autoimmune disease puts her at an increased risk to develop autoimmune hypothyroidism. Spontaneous hypothyroidism in iodine-sufficient areas is almost exclusively caused by autoimmunity. Hashimoto's thyroiditis and (in some rare cases) TSH-receptor blocking antibodies can also cause hypothyroidism that may be reversible.These blocking antibodies occupy the TSH receptor on the thyroid cells, preventing the gland from receiving TSH signals to produce T3 and T4. Treatment is levothyroxine replacement (1.6 mg/kg body weight), aiming for TSH levels within the low/normal range.

Thyroid hormone resistance is a genetically inherited condition in which mutations in the thyroid hormone receptor (THR) gene render the receptor less interactive with other cofactors in the signaling cascade; there can also be a lower affinity for T3, the active thyroid hormone. Most commonly, these patients are asymptomatic and the condition is detected during a routine laboratory analysis or after a family member is diagnosed. Thyroid hormone levels are elevated along with paradoxically elevated TSH levels. There is no current treatment for this condition.

TSH-producing pituitary tumors are rare pituitary adenomas that present more commonly as large lesions producing mass effects (e.g., headache, visual field impairment). Patients have elevated TSH and elevated thyroid hormones. The diagnosis is suspected in a patient with signs and symptoms of hyperthyroidism, elevated T3, free T4, and TSH levels, and a pituitary lesion on magnetic resonance imaging.

Iodine deficiency resulting in goiter and/or thyroid dysfunction is currently limited to endemic areas located far from the sea and where salt is not supplemented with iodine. Iodine is the main substrate used in the production of thyroid hormones and is mainly supplemented by diet. In its absence, a decreased production of T3 and T4 will result in increased levels of TSH and the development of a goiter. Treatment is with levothyroxine and an adequate supplementation of iodine.

Impaired thyroid hormone response to TSH is a condition in which the thyroid responds poorly to TSH due to mutations in the TSH receptor gene. Patients affected by this disorder present in 2 ways: if the resistance is partial, they present with inadequate production of thyroid hormones in lieu of increased TSH levels; if the resistance is complete, they present with congenital hypothyroidism, decreased response to TSH stimulation, and undetectable thyroglobulin levels. Treatment is levothyroxine replacement.
Explanation
The correct response is decreased axillary hair.

The clinical picture is suggestive of hypopituitarism. Hypopituitarism results in decreased levels of growth hormone (GH), gonadotropins (FSH, LH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), and prolactin. The onset is usually insidious. The clinical features of hypopituitarism depend on the underlying cause and the specific hormones that are deficient.

Thyroid stimulating hormone deficiency results in hypothyroidism. Patients present with feeling weak, drowsy, and fatigued. Some may complain of rough skin and decreased sweating. These symptoms may be accompanied constipation and cold intolerance.

Adrenocorticotrophic hormone deficiency results in adrenal insufficiency, which is characterized by fatigue, hypotension, and the loss of axillary as well as pubic hair.

Gonadotropin deficiency results in amenorrhea and genital atrophy in females, as well as impotence and testicular atrophy in males. Growth hormone deficiency results in growth failure in children, but has no clinically significant effects in adults. Prolactin deficiency results in failure of lactation in the postpartum period.

When panhypopituitarism is suspected, all target organ hormone function should be evaluated. Initial evaluation should be aimed at detecting TSH and ACTH deficiencies, because their deficiencies can cause life-threatening conditions: myxedema coma and adrenal crisis, respectively. Serum thyroxine (T4), triiodothyronine (T3), TSH levels, serum cortisol, and ACTH levels are low in hypopituitarism. Gonadotropin levels are low in panhypopituitarism, and GH measurements are generally helpful only in children. Thyrotropin-releasing hormone, insulin, and gonadotropin-releasing hormone can be administered intravenously together; then, TSH, GH, LH, FSH, ACTH, cortisol, prolactin, and glucose levels can be measured.

Diagnostic imaging includes skull X-rays of the sella turcica, which may provide evidence of the presence of pituitary tumors. High-resolution CT scans and MRI with contrast media may visualize smaller pathologies. The differential diagnoses for panhypopituitarism include anorexia nervosa, chronic liver disease, and polyglandular autoimmune disease. In anorexia nervosa, the secondary sexual characteristics are maintained even though the patients may be wasted and amenorrheic. Men with chronic alcoholic liver disease may develop testicular atrophy, but they have other features of chronic liver disease, and the serum levels of pituitary hormones are usually normal.

Treatment includes replacing the hormones of the hypofunctioning target glands. Treatment of GH deficiency in adults is unnecessary. When hypopituitarism is due to a pituitary tumor, specific treatment must also be directed to the tumor as well as to hormone replacement therapy. The management of such neoplasms may include surgical resection, bromocriptine, or irradiation.

Hyperhidrosis, insomnia, heat intolerance and diarrhea are symptoms of hyperthyroidism.
Explanation
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor predisposition. The diagnosis is often made in patients between 40 - 50 years of age; the disease is characterized by tumors of the parathyroid (83 - 97%), the pancreas (38 - 84%), and the pituitary (18 - 65%). Hyperparathyroidism is the most common manifestation. MEN1 is caused by mutations in the MEN1 gene on chromosome 11q13. The diagnosis is important because the treatment of tumors in patients with this mutation can be different than customary treatment.

Li-Fraumeni is an autosomal dominant tumor predisposition syndrome. Mutations in p53 have been identified in 40% of LFL. The tumors appear before 45 years of age. Usually, they are soft tissue sarcomas or osteosarcomas, but they can also manifest as brain cancer, breast cancer, leukemia, and other cancers. There are 3 criteria that are needed to be able to make this diagnosis:

the patient had a sarcoma before the age of 45
a first-degree relative had a diagnosis of any cancer before the age of 45
another first-degree or second-degree family member had a tumor before the age of 45 or a sarcoma at any age
Von Hippel-Lindau disease is an autosomal dominant tumor predisposition syndrome. The main criterion for the diagnosis is the presence of hemagioblastomas. Patients also can have multiple benign and malignant tumors of the central nervous system, kidneys, pancreas, adrenal glands, and paraganglia. The most malignant tumor that these patients can present with is renal cell carcinoma; it is seen in more than 50% of patients. Another tumor is the pheochromocytoma which is seen in 7 - 20% of patients. This tumor can produce a sudden release of catecholamines and result in death, especially pre or post-surgery.

Turcot syndrome is an inherited tumor predisposition. It is characterized by the presentation of colon cancer and brain cancer in the same patient. There are at least 2 types:

familial adenomatouspolyposis (FAP) and medulloblastoma caused by APC germline mutations
hereditary nonpolyposis colon cancer (HNPCC) and glioblastoma caused by germline mutations in 1 of the DNA mismatch repair genes (e.g., hPSM2 or hMLH1)
Cowden syndrome is an autosomal dominant tumor predisposition characterized by the development of multiple mucocutaneous lesions (hamartomas) and benign tumors. Patients also have a predisposition to a variety of neoplasias, particularly breast and thyroid cancers. This is related to mutations in the PTEN tumor suppressor gene.
Explanation
Diabetes type II is the correct answer for the clinical picture presented. This pathologic state consists of beta cell loss, but it also has other key characteristics that lead to its development; patients develop increased tissue insensitivity, also termed insulin resistance. This insensitivity leads to hyperactivity of the beta cells, producing excessive amounts of insulin, and over time the developed hyperplasia of the beta cells leads to impaired or even impeded function. Signs and symptoms that result from diabetes type II include but are not limited to: polyuria, polydipsia, chronic skin infections, or other indications of insulin resistance. Patients may be asymptomatic at the time of diagnosis. Diabetes should be high on one's differential diagnosis when a patient presents with frequent/chronic vulvovaginitis, which is part of the patient's complaint described above.

Diabetes type I is the most common type of diabetes mellitus in patients under the age of 20. Presenting symptoms can include polydipsia, polyuria, significant weight loss, and even a dangerous state of hypergylcemia that is referred to as diabetic ketoacidosis. Over 95% of type I diabetics develop this through autoimmune activity on the pancreatic islet cells; the remaining ~5% is idiopathic.

Hypothyroidism may from failure of the thyroid gland itself in secreting efficient levels of the main thyroid hormone free thyroxine, or FT4. Hypothyroidism may also occur because of deficiency of the secretion of thyroid stimulating hormone (TSH), which is secreted by the pituitary gland. Signs and symptoms highly suggestive of this disease state are weight gain, fatigue, lethargy, depression, weakness, cold intolerance, muscle cramps, and constipation.

Simply put, hyperthyroidism is a patient suffering from excessive serum levels of T4 and T3, while TSH levels are abnormally low. Signs and symptoms of the disease state include excessive sweating, weight loss, anxiety, palpitation, heat intolerance, palpitations, fatigue, and weakness.

Cushing's syndrome, which is also termed hypercortisolism, refers to the manifestations of excessive corticosteroids on the patient. Many of these cases are due to excessive ACTH secretion by a benign pituitary adenoma; however, other causes of excessive corticosteroids may lead to this condition, such as other non-pituitary secreting ACTH neoplasms as well as excessive secretion of t cortisol from the adrenal glands. In up to 30% of cases, the main cause may not be found. There are a multitude of symptoms and signs seen with Cushing's syndrome; they can include a moon facies, buffalo hump, abdominal purple striae, central obesity, menstrual irregularities, and even impaired wound healing.
Explanation
The correct response is an increase in her levothyroxine (Synthroid) dose.

This patient is pregnant and hypothyroid.The management of this patient requires careful titration of her levothyroxine (Synthroid) levels to maintain euthyroidism during pregnancy. Thyroid hormone is highly protein-bound, and any medical condition that changes the level of serum-binding proteins will change the level of free thyroid hormone available. For example, conditions that increase the level of serum-binding proteins (e.g., pregnancy and oral contraceptives) will decrease the level of free thyroid hormone. In such cases, the dose of replacement thyroid must be increased.

Conditions that necessitate a decrease in replacement doses include aging, chronic liver disease, and protein-losing conditions (e.g., nephropathy and enteropathies). While free T4 levels estimate the level of thyroid hormone available, the variation in levels does not reflect the metabolic needs of patients. TSH assessment provides a better reflection of decreasing levels of available thyroid hormone; however, TSH levels lag behind changes in free T4 levels. TSH should be repeated no earlier than 4 weeks after any changes are made in thyroid doses; it is important to note that it may take 8 weeks for the TSH to stabilize after the change is made.

Some patients may note an improvement in mood, memory, and cold tolerance with the addition of triiodothyronine to their regular thyroid replacement. In the patient presented, however, there was no problem with her thyroid replacement before her pregnancy; therefore, it is unlikely that she will need T3 added to her regimen. Free T3 levels are unnecessary in the management of this patient.

The increased T4 dose requirement is typically seen by the 1st trimester of pregnancy. Monitoring the TSH regularly throughout pregnancy will allow adjustments to be made in the levothyroxine (Synthroid) dose. The goal of thyroxine replacement is to maintain serum TSH in the normal range. It must be remembered that hypothyroidism during pregnancy is associated with hypertension and premature labor. Dose adjustments upwards are usually in the range of 25 - 50% of the normal daily thyroid replacement dose.
Explanation
The correct response is thyroid-stimulating hormone.

This woman has hypothyroidism. She has the classic symptoms, which are weight gain, depression, constipation, myalgias, cold intolerance, fatigue, deep voice, bradycardia, and dry skin and hair. It is a very common condition that is seen mostly in middle aged and elderly women; however, it can also be seen in young patients. 1.5 - 2% women above 60 years and up to 5 - 15% women above 65 years of age may be affected.

Hashimoto's thyroiditis is an autoimmune condition, and it is the most common cause of hypothyroidism in the western world, whereas iodine deficiency is the etiological factor in the developing countries. Hashimoto's thyroiditis may present as hypothyroidism, goiter, silent thyroiditis, or post-partum thyroiditis. Other symptoms of hypothyroidism include puffy eyes from periorbital edema, shortness of breath, exercise intolerance, decreased appetite, somnolence, blurred vision, and decreased sweating. Anemia may be present, which can be normocytic normochromic due to decreased red cell mass or, in 10% of cases, autoimmune thyroiditis. Macrocytic anemia due to pernicious anemia may be seen. Menstrual irregularities are common and could be amenorrhea, oligomenorrhea, or menorrhagia. Infertility and early pregnancy loss may be seen. Muscle weakness and carpal tunnel syndrome may occur. TSH will be high and T3, T4 low. TSH is the earliest and most sensitive indicator of primary hypothyroidism. Sensitive third generation TSH assays are now available for easy diagnosis. Anti-thyroid peroxidase (TPO) antibodies and antibodies to thyroglobulin may also be done. Treatment is by replacement of thyroxine for life, since it is a permanent condition. The recommended replacement dose for an average 70 kg adult is 1.6 mcg/kg/day, but the dose may vary from 50-200 mcg daily. In the elderly, it is a good idea to start at a lower dose, since thyroxine can aggravate coronary ischemia. It should be taken in the morning on an empty stomach.

Metabolic panel is non-diagnostic, and so is a complete blood count. Anemia may be present occasionally.

FSH and LH are done when perimenopause is suspected. Some of her symptoms, such as depression, myalgias, and fatigue, are also seen in perimenopausal women; however, weight gain, cold intolerance, and bradycardia are not seen.

Lipid profile is a screening test for adults and should be done in this patient also. It is not a diagnostic indicator of the underlying condition, which is hypothyroidism.
Pituitary Gland
Explanation
Thyrotropin is released by the pituitary gland. The pituitary gland releases thyrotropin/Thyroid Stimulating Hormone (TSH) in response to insufficient levels of thyroid hormone. Communication between the pituitary gland and the thyroid gland through TSH levels controls the levels of thyroid hormone in the blood. If the levels of thyroid hormone are low, then the levels of TSH will rise. The measurement of TSH in the blood is taken as a measure of thyroid function. High levels of TSH would indicate low levels of thyroid hormone. Thyrotropin hormone is not released by pancreas, hypothalamus adrenal, or the thyroid gland.

Graves' disease is a type of hyperthyroidism caused by a generalized overactivity of the entire thyroid gland. The patient appears hot and flushed, and the thyroid gland enlarges in this condition. It is believed that Graves' disease is an autoimmune disorder. Antibodies are produced against 4 thyroid antigens, namely thyroglobulin, thyroid peroxidase, sodium-iodide symporter, and the thyrotropin receptor. The antibody against the thyrotropin receptor-TSI is the principal autoantibody of Graves' disease responsible for the manifestations of hyperthyroidism. Autoantibodies are produced against certain proteins on the surface of thyroid cells, stimulating those cells to overproduce thyroid hormones, resulting in the overactive thyroid. The onset of the disease is gradual, and the symptoms may be mistaken for nervousness due to a stressful life situation. Weight loss occurs, and this is followed by other symptoms such as trembling, muscle weakness of the upper arms and thighs, and insomnia. Thyroid function tests and the presence of TSI help in establishing the diagnosis of Graves' disease.
Blood glucose after an overnight fast (FBG)
Explanation
This woman's nocturia and her recurrent vaginal candidiasis, which is a common correlate of hyperglycemia in women, are symptoms of diabetes mellitus. Women who are diabetic are more prone to vaginal yeast infections due to vaginal secretions containing greater amount of glucose than normal. Yeast cells are nourished by this excess glucose. Additionally, acute hyperglycemia can affect all major components of innate immunity, thereby impairing the ability of the host to combat infection.

The standard means of diagnosing diabetes is measurement of FBG; the measurement should be repeated if the value is greater than 110 mg/dl. The current criteria considered diagnostic of diabetes is the finding of an FBG level of 126 mg/dl on more than one occasion. An FBG of 110 to 126 mg/dl is indicative of abnormal glucose metabolism, with higher values indicating an increased likelihood of progression to diabetes.

Immediate measurement of blood glucose concentration is an incorrect response. A determination of random blood glucose level is diagnostic if that level is greater than 200 mg/dl in a symptomatic patient. Random blood glucose values vary considerably more than do FBG values and thus are not as reliable for establishing a diagnosis.

Point-of-Care (POC) hemoglobin A1c (HbA1c) level is an incorrect response. Although in 2009, an international expert committee recommended the A1c test as one of the tests available to help diagnose type 2 diabetes and prediabetes, point-of-care (POC) A1c assays are not sufficiently accurate at this time to use for diagnostic purposes. HbA1c as a diagnostic test should be performed using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized.

Oral glucose tolerance test is an incorrect response. OGTT are quite sensitive in the detection of diabetes, and the 50 g and 100 g tests have a clear place in the diagnosis of gestational diabetes; however, these tests are more expensive and inconvenient for patients than measurement of FBG, and their results are less reproducible. Because abnormalities in fasting and postprandial glycemia tend to progress in tandem, FBG measurement has supplanted the oral glucose tolerance test for the diagnosis of diabetes (except during pregnancy).
Explanation
The correct answer is papillary thyroid carcinoma. The patient has 3 risk factors for thyroid cancer, including female gender, age over 40, and history of radiation to face/neck region for acne. Thyroid function tests are typically normal in patients with thyroid cancers. The diagnostic findings of a solid, cold nodule are also suspicious for a thyroid cancer. However, those findings can be seen in benign nodules as well. Given the fact that papillary thyroid carcinoma is the most common type of thyroid cancer (about 60% of all thyroid cancers) and the patient has a history of radiation to face/neck region, the most likely type of thyroid cancer in this case is papillary.

Hashimoto's thyroiditis is not the correct answer. While thyroid nodules can be present in cases of Hashimoto's thyroiditis, they are usually "multinodular" rather than a solitary thyroid nodule. Patients would also usually have more complaints upon presentation. In addition, the physical examination is likely to be normal or reveal a goiter with or without multiple nodules. The thyroid function testing would not be normal. Most commonly, the TSH would be elevated in the face of decreased T4.

Medullary thyroid carcinoma is not the correct answer, as this is not the 'most likely' diagnosis in this case. The patient is at risk for thyroid cancer, but her history of radiation to face/neck region and the fact that papillary carcinoma is much more common (60% as opposed to 5% of all thyroid cancers) make her type of cancer more likely to be papillary rather than medullary.

Parathyroid cyst is not the correct answer. A parathyroid cyst falls under the category of a benign cyst of the thyroid. Thyroid cysts make up only 15 - 25% of thyroid nodules, and benign cysts make up 85% of that group. A parathyroid cyst is 1 of the many types of benign thyroid cysts, and it would not be solid on an ultrasound.

Graves' disease is not the correct answer. Patients will typically have more complaints and positive symptoms when they have Graves' disease. In addition, the examination of their thyroid is not likely to have a solitary thyroid nodule. The thyroid function tests would not be normal and are most likely to show a decreased TSH and elevated T4.
A 62-year-old woman presents to her OB/GYN clinic for an annual exam. She reports she has not felt well for several months, but her family practice physician retired, and she kept hoping her symptoms would improve. She reports stretch marks and a weight gain of about 20 pounds, which is especially noticeable in her face. She feels fatigued; she has no sex drive, and she feels more irritable. She notes increased dark hairs growing on her chin. The patient reports easy bruising, but she denies blood in the stools. She denies fever, chills, foreign travel, changes in sexual partners, and suicidal thoughts.

Her past medical history is significant for asthma, with periodic hospitalizations for asthma attacks. She was menopausal at the age of 51. She has had no surgeries. She takes prednisone 40 mg daily, an inhaler with fluticasone propionate/salmeterol 2 times daily, and an albuterol inhaler as needed for her asthma. She has no allergies. She is retired; she lives at home with her husband, and she denies use of tobacco, alcohol, and street drugs.

BP is 162/92 mm Hg, and pulse is 98. Respiratory rate is 12. Weight is 170 lbs, and height is 63", making her BMI 30.11.

On physical exam, the patient has a rounded, full face; she appears fatigued, but she is pleasant and cooperative. Striae are noted on her abdomen, and hirsutism is present on her chin and abdomen. There appears to be a large fat deposit on the upper back, and she has an obese abdomen, with some muscle wasting on the patient's extremities. The remainder of her exam is normal.



Question
What is the most appropriate intervention for this patient's current condition?

Answer Choices
1 Counsel the patient about normal post-menopausal symptoms
2 Perform dexamethasone suppression test
3 Refer to dietitian for weight loss
4 Stop the inhaled medications
5 Taper off the daily prednisone
Explanation
This patient is presenting with Cushing syndrome, an excess of glucocorticoids; it is most likely iatrogenic, caused by her daily prednisone. The most appropriate intervention is to taper off her daily prednisone. This common steroid is often given for acute flares of chronic diseases. However, chronic daily use can lead to a glucocorticoid excess known as Cushing syndrome. Cushing syndrome is characterized by central obesity, muscle wasting, hirsutism, a 'buffalo hump' on the upper back, 'moon facies', weight gain, hypertension, decreased libido, irritability, and several other possible signs/symptoms. Unrecognized and untreated Cushing syndrome can lead to osteoporosis. Tapering off the prednisone (rather than immediate discontinuation) helps prevent sudden adrenocortical insufficiency.

While it would be acceptable to counsel the patient about normal post-menopausal symptoms at her GYN annual exam, her current condition cannot be attributed to normal menopausal changes. Normal post-menopausal changes include vasomotor symptoms (such as hot flashes and night sweats) and vulvovaginal changes (such as atrophy, vaginal dryness and dyspareunia). Some women may experience some mild weight gain and irritability, but the remainder of this patient's symptoms are not related to a drop in sex hormones.

When Cushing syndrome is suspected, it is common to perform a dexamethasone suppression test. The dexamethasone is an exogenous glucocorticoid that will negatively feedback on the pituitary and should lower the adrenocorticotropic hormone and result in lowered cortisol levels in the serum. However, while the patient is taking daily corticosteroids, the test will be altered. This patient should be tapered off the prednisone, and if symptoms persist, a dexamethasone test can be done.

This patient's concerns should not be attributed to a weight-gain only issue and simply referred to a dietitian for weight loss. Weight gain is a common side effect from exogenous corticosteroids and should reverse with discontinuation of the medication. A dietitian referral could be offered in addition to treatment of this patient's Cushing syndrome, but it should not be the primary treatment.

This patient's inhaled fluticasone propionate is also a steroid medication, and it is given to reduce inflammation in the airways. Typically, the inhaled and intranasal steroids at usual doses are considered low enough strength that they will not lead to corticosteroid excess and Cushing syndrome. The systemic steroid, prednisone, is much more potent and is the likely culprit for this patient's symptoms. The albuterol inhaler is a short-acting beta-agonist and should not be discontinued in patients with severe asthma; therefore, it would be inappropriate to stop this patient's inhaled medications.
Explanation
The correct response is a 24-hour urinary free cortisol level.

This patient is demonstrating signs and symptoms consistent with Cushing's syndrome. The diagnosis of Cushing's syndrome due to endogenous overproduction of cortisol requires the demonstration of inappropriately high serum cortisol or urine cortisol levels. Currently, 4 methods are accepted for the diagnosis of Cushing's syndrome: urinary free cortisol level, low-dose dexamethasone suppression test, evening serum and salivary cortisol level, and dexamethasone-corticotropin-releasing hormone test.

Urinary free cortisol determination has been widely used as an initial screening tool for Cushing's syndrome because it provides measurement of cortisol over a 24-hour period. A valid result depends on adequate collection of the specimen. Urinary creatinine excretion can be used to assess the reliability of the collection. Urine free cortisol values higher than 3 - 4 times the upper limit of normal are highly suggestive of Cushing's syndrome.

A potassium hydroxide (KOH) preparation is a diagnostic test used to assess for the presence of a fungal disorder.

Agents that inhibit steroidogenesis (e.g. mitotane, ketoconazole, metyrapone, aminoglutethimide, trilostane, and etomidate) have been used to cause medical adrenalectomy. These medications are used rarely, and they are often toxic at the doses required to reduce cortisol secretion. For instance, ketoconazole's prescribing information was revised to include a black box warning regarding hepatotoxicity, including fatalities and liver transplantation. Therefore, medical treatment should be initiated cautiously; ideally, it should be done in conjunction with a specialist. Ketoconazole has been the most popular and effective of these agents for long-term use and usually has been the agent of choice. However, the FDA has issued a warning that states clinicians should no longer prescribe ketoconazole, except to treat some life-threatening fungal infections; this is due to increased risk for severe liver injury, adrenal insufficiency, and adverse drug interactions.

Imaging studies for Cushing's syndrome should be performed after the biochemical evaluation has been performed. The rationale for this is that unguided imaging of the pituitary or adrenal glands may yield a 10% incidence of incidental nonfunctioning pituitary or adrenal adenomas, which may mislead one from proper therapy and surgery. Ideally, the biochemical abnormalities should reconcile with the anatomic abnormalities before definitive therapy is offered.

An abdominal CT scan is recommended if a primary adrenal problem is suspected. The presence of an adrenal mass larger than 4 - 6 cm raises the possibility that the mass is an adrenal carcinoma.

Corticosteroid therapy (e.g. prednisone) is not appropriate treatment for a patient experiencing hypercortisolism.
A 19-year-old man has known type I diabetes on insulin; he is brought to the ER by his family with a history of clouding of consciousness, vomiting, shortness of breath, and weakness. Symptoms have present since the morning. He also has a 2-day history of cough with productive sputum and fever. He is known to be non-compliant with insulin and diet and has had multiple ER visits. At home, his mother checked his blood sugar on his glucometer, which reported a "high level", signifying more than 500 mg/dl. On examination he is found to have a temperature of 101.5° F, pulse 110/min, BP 100/58 mm Hg, and respirations of 24/ minute. Skin and mucosa are very dry. Auscultation reveals crackles at the base of the right lung, tachycardia, and normal bowel sounds. He is drowsy but arousable and oriented. Labs are ordered, and supportive measures are started with fluids and insulin.



Question
The labs for the above patient show a blood sugar of 950 mg/dl, sodium 129 meq/L, chloride 91 meq/L, potassium 3.2 meq/L, BUN 35 mg/dL, creatinine 1.5 mg/dL, bicarbonate of 18 meq/L, anion gap 20, WBC 13,000/uL, serum ketones positive, and serum osmolality 300 mosm/kg. CXR shows right lower lobe consolidation and EKG shows tachycardia only. The best combination for the correct management of this patient includes fluids and what else?

Answer Choices
1 SC insulin every 4 hours, potassium, bicarbonate, and antibiotics
2 Insulin drip, potassium, and antibiotics
3 Bolus insulin IV then SC every 4 hours, potassium, and antibiotics
4 IV insulin every 4 hours, potassium, and antibiotics
5 SC insulin every 2 hours, potassium, and antibiotics
Explanation
The above summary is depicting diabetes type I, which is the most common type of diabetes mellitus in patients under the age of 20. Presenting symptoms can include polydipsia, polyuria, significant weight loss, or even a dangerous state of hyperglycemia known as diabetic ketoacidosis. Over 95% of type I diabetics develop diabetic ketoacidosis through autoimmune activity on the pancreatic islet cells; in the remaining ~5% of cases, it is idiopathic.

Acute pancreatitis (acute inflammation of the pancreas) does not usually lead to permanent destruction of the pancreatic islet cells. Patients who develop acute pancreatitis are adults with significant gallbladder disease and/or a history of heavy alcohol use.

Hypothyroidism may be the result of the thyroid gland's failure to secret efficient levels of the main thyroid hormone free thyroxine, or FT4. Hypothyroidism may also occur because of a deficiency of the secretion of thyroid stimulating hormone (TSH), secreted by the pituitary gland. Although hypothyroidism can virtually affect almost every body system in terms of signs and symptoms, it does not lead to autoimmune damage of the pancreatic islets.

Diabetes type II does consist of beta cell loss, but there are also other key characteristics that lead to this disease state. Patients develop increased tissue insensitivity, which is also termed insulin resistance. This insensitivity lead to hyperactivity of the beta cells, producing excessive amounts of insulin; over time, the developed hyperplasia of the beta cells leads to impaired or even impeded function. The majority of the time, this is not due to autoimmune issues.

Cushing's syndrome (or hypercortisolism) refers to the manifestations of excessive corticosteroids on the patient. Many of these cases are due to excessive ACTH secretion by a benign pituitary adenoma; however, other causes of excessive corticosteroids may lead to this condition, such as other non-pituitary secreting ACTH neoplasms and excessive secretion of t cortisol from the adrenal glands; in up to 30% of these cases, the main cause may not be found. There are a multitude of symptoms and signs seen with Cushing's syndrome, and glucose tolerance impairment secondary to insulin resistance is one of them.
Order LH, FSH, testosterone and estradiol
Explanation
Approximately 70% of pubertal boys develop at least breast buds during adolescence, though some will have more extensive growth. This is probably a result of low testosterone in relation to estradiol levels thus laboratory evaluation should include testosterone, estradiol and gonadotropins to assess levels. This would effectively rule out conditions that could cause markedly abnormal levels, such as Klinefelter syndrome, the most common sex chromosome disorder, and the most common cause of hypogonadism and infertility in men. There are decreased levels of testosterone and elevated follicle-stimulating and luteinizing hormones. Karyotype analysis will reveal 1 or more extra X chromosomes.

Physiologic gynecomastia usually resolves by 18 years when adult androgen/estrogen ratios are achieved.

The incidence of breast enlargement peaks between the ages of 13-15 years during Sexual Maturity rating or Tanner staging 2 to 3 and may be unilateral or bilateral. Reassurance concerning the benign nature of the condition is usually all that is needed. Gynecomastia that occurs at other times in age or sexual development (excluding newborns) or that evolves rapidly would warrant further investigation.

Surgical removal of the enlarged breast glandular tissue should be considered in boys who have had very persistent gynecomastia and who have completed puberty.

Ultrasound imaging of the breast can be used to distinguish between solid tumors and fluid-filled cysts. Breast cancer in adolescents is extremely rare. Tumors tend to be slow growing, well differentiated, firm and painless.

A urine drug screen would point to possible marijuana use that can be seen with gynecomastia when it is smoked heavily. There is little concern in this patient who is doing well at school, denies substance abuse, and whose parent does not express this concern.

Obese pubertal boys commonly present with gynecomastia due to the accumulation of fat in the upper segment of the body both subcutaneously and intra-abdominally. The breasts are often greater in size and more persistent than in usual physiologic gynecomastia. In such a case, a nutrition consult would be indicated; however, on exam this patient was seen to be proportional for both height and weight.
Explanation
The correct answer is to eliminate 4 units of NPH insulin before dinner. The first step in managing insulin therapy is to eliminate low blood sugars. This patient is experiencing nocturnal hypoglycemia, which stimulates the release of counter-regulatory hormones to increase the blood sugar, thereby resulting in rebound hyperglycemia. This would account for his elevated fasting blood sugar readings. The NPH insulin has an onset of action of 1 - 2 hours and a peak effect in 6 - 12 hours, so decreasing the dinner dose 10 - 20% will decrease the likelihood of 3:00 am hypoglycemia and the subsequent morning rebound hyperglycemia.

Eliminating 2 units of regular insulin before dinner may have some effect on the patient's 3:00 am hypoglycemia, but at the expense of higher 11:00 pm blood sugar readings. The regular insulin has an onset of action in 30-60 minutes, with a peak effect at 2-4 hours. The current dinner dose of 10 units of regular insulin is providing rapid-acting coverage for that meal with an acceptable average blood sugar of 140 mg/dL at 11:00 pm. Eliminating 2 units before dinner will result in higher blood sugars at 11:00 pm and suboptimal control.

Adding 4 units of regular insulin before breakfast will serve to lower the elevated fasting blood sugars, but will do nothing to correct the nocturnal hypoglycemia, which is the main problem. Adding this extra rapid-acting insulin is a reactive response rather than a proactive step to control blood sugars.

Adding 2 units of NPH insulin before breakfast will have minimal effect to correct the elevated morning blood sugars or the nocturnal hypoglycemia.

Adding 2 units of NPH insulin before dinner will make the nocturnal hypoglycemia worse.
Explanation
Routine colonoscopies should be scheduled for this patient.

This patient's most likely diagnosis is acromegaly. Acromegaly is nearly always caused by a pituitary adenoma.

Patients should be advised that, if untreated, one's life span is decreased by an average of 10 years. Patients must receive lifelong follow-up, with regular monitoring of serum GH and IGF-I levels. Serum GH levels over 5 ng/mL and rising IGF-I levels usually indicate a recurrent tumor. Both IGF-I and GH levels correlate with mortality; survival improves greatly if GH and IGF-I can be normalized.

Patients must receive lifelong follow-up, with regular monitoring of serum GH and IGF-I levels.

Both an initial colonoscopy and echocardiogram are recommended. Colon polyps and mortality from colonic malignancy are more likely to develop in patients with acromegaly. As such, increased surveillance for colorectal cancer is recommended. Based on a cohort study of patients hospitalized for acromegaly (Denmark 1977-1993; Sweden 1965-1993) linked to tumor registry data for up to 28 years of follow-up, individuals with acromegaly have higher rates of small intestine, colon, rectal, kidney, and bone cancer.

Patients with acromegaly have increased morbidity and mortality from cardiovascular disorders and progressive acromegalic symptoms. Complications of acromegaly include hypopituitarism, hypertension, glucose intolerance or frank diabetes mellitus, cardiac enlargement, and cardiac failure. Strict control of comorbidities, including diabetes and hypertension, are essential.

This patient is not at risk for demineralized bone; a bone density (DEXA) scan is not recommended in patients with acromegaly.
Rapid deep breathing
Explanation
The patient described here likely has diabetic ketoacidosis, a form of metabolic acidosis. Her respiratory response to metabolic acidosis should be rapid deep breathing (Kussmaul breathing), leading to respiratory alkalosis.

Symptoms of diabetic ketoacidosis may be highly variable; symptoms include nausea, vomiting, thirst, polyuria, abdominal pain, and shortness of breath.

Physical findings may include hypotension (secondary to volume depletion), tachycardia, dry mucous membranes, hypercapnia, abdominal tenderness, and lethargy.

In patients with known diabetes, precipitating events may include inadequate insulin intake, infections (e.g., urinary), myocardial infarctions, and pregnancy; history and related diagnostic testing should focus on these precipitating factors.

In patients with both known and new onset diabetes, suspicion of diabetic ketoacidosis warrants an evaluation of serum glucose, ketones, and basic chemistries. Potassium is often elevated due to cellular shift and may fluctuate with insulin treatment; bicarbonate is often decreased secondary to the acid buffering, and urea nitrogen is often elevated due to volume depletion.

Management focuses on correcting salt and water deficits over the first 24 hours (first with saline and then with 1/2 normal saline when hemodynamically stable); administering intravenous insulin (0.15 units/kg bolus, then 0.1 unit/kg/hour); and frequent monitoring of serum glucose, potassium and bicarbonate, and acetone during treatment.
The ability of metformin to decrease the production of glucose by the liver
Explanation
Metformin (Glucophage®) is a hypoglycemic drug that is effective only in the presence of insulin because it acts to increase the action of insulin. It does not alter insulin production. One important mechanism by which metformin works is decreasing the production of glucose by the liver. Metformin acts by activating the AMP-activated protein kinase (AMPK), a major cellular regulator of lipid and glucose metabolism. In addition, glucose utilization by muscle is increased. Given in combination with a sulfonylurea, metformin lowers blood glucose concentrations more than either drug alone. This treatment is not effective for patients with insulin-dependent diabetes (Type I) because the beta cells are not viable.

Type II diabetes mellitus, also called non-insulin-dependent diabetes mellitus (NIDDM), has a slow onset and is typically seen in patients over the age of 40. Insulin is present, but it is not properly utilized. Controlling diet can often control NIDDM. In cases where diet does not lower blood glucose levels, drugs called oral hypoglycemic agents (such as the sulfonylureas and metformin) are prescribed.

Sulfonylurea agents (glyburide, glipizide, and glimepiride) act to lower blood glucose levels by causing the pancreas to secrete more insulin and by allowing target cells to better use the insulin. The main mechanism of action of the sulfonylurea drugs is to stimulate the release of endogenous insulin from the beta cells of the pancreas.

The major insulin responsive glucose transporter, GLUT4, is not affected directly by metformin. The conversion of proinsulin to insulin occurs in the secretory granules as they mature, and it is regulated by glucose levels. Metformin has been shown to have no effect on the oxidation of fatty acids such as oleate.
Thyrotropin receptor antibody assay
Explanation
Your patient has signs and symptoms of Grave's disease. Grave's disease is an autoimmune disease caused by anti thyroid-stimulating hormone (TSH) receptor. Thyrotropin receptor antibody assay is not required for the diagnosis of Grave's disease, but it will confirm the diagnosis. Sometimes this test is needed to establish the cause of exophthalmos (e.g., in the absence of thyrotoxicosis) or to predict fetal or neonatal thyrotoxicosis. Among the choices offered, it is the most accurate test for Graves' disease.

You can order an image of pituitary gland in secondary hyperthyroidism, when both TSH and T4 are high; that is not the case in your patient.

You can order free T3 levels in the case of hyperthyroidism when TSH is low and T4 normal and you think that patient might have T3 thyrotoxicosis. Usually those patients will have mild disease, but, otherwise, the clinical picture may be similar to other forms of hyperthyroidism. Elevation of T3 alone can also produce symptoms of thyrotoxicosis, but there will be no exophthalmos.

Fine needle biopsy is indicated to rule out or confirm cancer of the thyroid gland. Patients with thyroid cancer usually are euthyroid and have normal TSH and non-functional ("cold") nodule.

Color Doppler flow exam may help when a possible nodule is detected on physical exam or may show hypoechogenicity to confirm the diagnosis of Hashimoto's thyroiditis or demonstrate intense vascularity in the case of Graves' disease. However, ultrasound of thyroid gland rarely has a value in the diagnosis of hyperthyroidism and is not specific.
Explanation
A patient with hyperthyroidism could experience excessive sweating, heat intolerance, heart palpitations, and a myriad of other possible symptoms. Excessive secretion of the circulating free thyroid hormones affects multiple organ systems, resulting in this myriad of potential symptoms. The facts that the patient is female, in her third decade of life, and has another autoimmune disorder are also risk factors for hyperthyroidism.

Hair loss, decreased energy, and dry skin are symptoms of hypothyroidism rather than hyperthyroidism. Hypothyroidism is typically an autoimmune disease or a result of prior radiation therapy or thyroid surgery. While some of the symptoms can overlap with those of hyperthyroidism, that is not typically the case with those listed. In fact, a patient with hyperthyroidism is likely to have hyperactivity and irritability rather than decreased energy. They are also more likely to have excessive sweating as opposed to dry skin.

Cramping, numbness around mouth, and tingling in distal extremities are symptoms that could occur in a patient with hypoparathyroidism. This disorder is a result of a deficiency of parathyroid hormone from congenital absence, injury, surgery, or other diseases. Most of the symptoms associated with hypoparathyroidism are a result of hypocalcemia.

Bone pain, flank pain, and anxiety could occur in a patient who has hyperparathyroidism. This disorder is characterized as a dysfunction in the body's regulatory system for parathyroid hormone. While up to 75% of patients can be asymptomatic, the hypercalcemia associated with hyperparathyroidism can result in the classic complaints of painful bones, renal stones (causing flank pain), abdominal groans, and psychic moans.

Dizziness, salt craving, and chronic diarrhea are symptoms that could occur in a patient with Addison's disease. Adrenal gland insufficiency can occur as a result of autoimmune inflammation and multiple other causes, and it is more common in women. Other symptoms that can commonly occur are weakness, fatigue, anorexia, nausea, vomiting, depression, and myalgias.
A 43-year-old Caucasian woman presents for evaluation of menstrual irregularities over the past 6 months, despite of history of prior regular menses. She had a bilateral tubal ligation (BTL) and reports multiple negative home pregnancy tests. The patient also notes weight gain and increased girth in her abdomen. She reports easy bruising without a history of trauma; she also notes the new development of "stretch marks" on her torso, and there is also weakness in her arms and legs. She denies any health changes, medications, or stressors in relation to these changes. She denies hot flashes, night sweats, and frank depression; however, she admits to some mood swings and poor libido. The patient is frustrated that her health fair labs (which include complete blood count, complete metabolic panel, lipid panel, and thyroid stimulating hormone) were all normal and do not explain her symptoms.

Her past medical history reveals no chronic conditions; she does not take any medications, and she has no known drug allergies. Her only surgery was the BTL. She lives with her husband and 3 children. She works as a retail clerk and walks for exercise. She denies the use of tobacco, alcohol, and drugs.

Her blood pressure is 154/92. Chart review demonstrates weight gain of 15 pounds over 6 months. She has had normal blood pressures in the past.

On physical exam, you observe an overweight woman with an especially rounded, full face. She also has a fatty fullness to her neck region, and there is some central obesity; however, her arms show some muscle wasting. She has purple striae on her torso. Her skin also appears thinned, with multiple bruises. Hirsutism is observed on the patient's chin, abdomen, and breasts. The remainder of her exam was unremarkable.

Testing confirms elevated ACTH and high cortisol levels in the evening and after dexamethasone suppression, as well as a pituitary macroadenoma as the cause.



Question
What prescription medication may be indicated after the surgical removal of her tumor?

Answer Choices
1 Aldosterone
2 Insulin
3 Levothyroxine
4 Parathyroid hormone
5 Prolactin
levothyroxine
Explanation
This patient presents with a multitude of signs and symptoms (weight gain, menstrual irregularity, mood swings, poor libido, moon facies, fat depositions, proximal limb weakness, central obesity, skin thinning, purple striae, and easy bruising) that support a diagnosis of Cushing's syndrome or Cushing's disease. The most common cause of Cushing syndrome is considered iatrogenic, from administering exogenous steroids, such as prednisone. The next most common cause is known as Cushing's disease, and it results from increased adrenocorticotropic hormone (ACTH) secretion from pituitary, which causes increased adrenal production of cortisol. This patient's tests indicate Cushing's disease, with a pituitary macroadenoma. Surgery is indicated. If damage occurs to the anterior pituitary, it can affect hormone secretion. Often, replacement of levothyroxine, estrogen, progesterone, and possibly desmopressin may be needed.

Aldosterone, which regulates sodium balance, is a hormone produced by the adrenal glands. Rarely, Cushing's disease can be caused by an adrenal neoplasm, but those cases are considered non-ACTH dependent. This patient would not be expected to have any adrenal issues following pituitary surgery.

Insulin, which regulates glucose metabolism, is produced in the pancreas. This patient's Cushing's disease and subsequent pituitary surgery should not lead to the requirement of insulin prescription.

Parathyroid hormone, which regulates calcium balance, is produced by the parathyroid glands. These glands can be damaged during thyroid surgeries and require subsequent management of calcium. However, this patient's parathyroid hormone should not be altered by her pituitary surgery.

Prolactin, which primarily regulates milk production, is produced by the anterior pituitary gland. This patient would potentially experience problems with prolactin production following pituitary surgery if she were lactating. However, she has had surgical sterilization; therefore, she has no need for prolactin production.
Cushing Disease
Explanation
This patient has a pituitary adenoma that is secreting ACTH. Cushing's disease refers to excessive secretion of ACTH by the pituitary. A pituitary adenoma is the most common cause of pituitary hypersecretion of ACTH. The increase in ACTH secretion results in hyperplasia of the adrenal cortex and a subsequent increase in glucocorticoid release. Characteristics of glucocorticoid excess include depression, truncal obesity, purple striae, round face (moon facies), and hypertension.

Addison's disease is primary adrenal insufficiency. The most common cause of Addison's disease is autoimmunity; tuberculosis is another cause. The symptoms seen with Addison's disease include weight loss, lethargy, hyperpigmentation, nausea, vomiting, and hypotension. Hyponatremia and hyperkalemia can be seen because of the lack of mineralocorticoids. When there is decreased stimulation of the adrenal cortex due to a decrease in ACTH, it is called secondary adrenal insufficiency.

Conn's syndrome is due to excessive mineralocorticoids, usually due to an adenoma that is secreting aldosterone. Conn's syndrome results in hypernatremia and hypokalemia; there is an associated hydrogen loss, as well. There will be hypertension.

A distinction exists between Cushing's disease and Cushing's syndrome. Cushing's disease refers specifically to excessive secretion of ACTH by the pituitary. In Cushing's disease, the excessive ACTH secretion by the pituitary results in an increase in glucocorticoid release by the adrenal glands. Cushing's syndrome refers to the effects of excessive glucocorticoids (other than those due to a pituitary cause); therefore, Cushing's syndrome is due to excessive glucocorticoids. There will be hypertension with both Cushing's disease and Cushing's syndrome.

Nelson's syndrome is seen in patients who have had a bilateral adrenalectomy for Cushing's disease; there is the subsequent development, or progression, of an ACTH-secreting pituitary tumor.
The most likely diagnosis in this patient is Graves' disease.

Thyrotoxicosis occurs due to thyroid hormone excess, the etiology of which varies from Graves' disease, toxic multinodular goiter, toxic adenoma, thyroiditis, and even functioning metastasis.

Symptoms of thyrotoxicosis include hyperactivity, irritability, dysphoria, heat intolerance and sweating, palpitations, fatigue, weakness, weight loss with increased appetite, diarrhea, polyuria, and menstrual irregularities.

Graves' disease is the most common cause of thyrotoxicosis. It is an autoimmune disease in which thyroid-stimulating autoantibodies stimulate thyroid receptors to secrete thyroxine. It is more common in women and can be identified by radionucleotide scan in which the whole thyroid shows increased uptake. Here the patient has all Graves' disease characters: she is middle aged with thyrotoxic characters and her Tc-99 scan shows the characteristic Graves' pattern.

Toxic multinodular goiter is another cause of thyrotoxicosis in which there are multiple nodules that can be felt with palpation, and it is shown to be hot or active with the radionucleotide scan. It shows localized or patchy uptake in the scan pictures.

Hashimoto thyroiditis is an inflammatory condition that follows viral infection. It is associated with a brief period of hyperthyroidism that is followed by hypothyroidism, which may persist throughout life. On Tc scan, it shows decreased uptake.

Factitious hyperthyroidism is due to ingestion of the thyroid hormone. Usually this happens in nurses, physicians, or those who have access to medicine. It can be detected by measuring T3 and T4. There is also decreased uptake on thyroid scan.

Toxic adenoma is a benign neoplastic nodule, which actively secretes thyroxine. It shows localized or patchy uptake of Tc 99 on thyroid scan.
Explanation
The correct response is hydrocortisone.

Given this patient's strong autoimmune history, the most likely diagnosis is Addison's disease. The most common cause of Addison's disease is idiopathic autoimmune adrenocortical insufficiency resulting from autoimmune atrophy, fibrosis, and lymphocytic infiltration of the adrenal cortex. Manifestations include insidious hyperpigmentation of the skin (most often prominent on the sun-exposed areas of the skin, extensor surfaces, knuckles, elbows, knees, and scars formed after the onset of disease), progressive weakness, fatigue, poor appetite, and weight loss. Prominent gastrointestinal symptoms may include nausea, vomiting, and occasional diarrhea; dizziness with orthostasis due to hypotension occasionally may lead to syncope. The comprehensive metabolic panel reveals hyponatremia, hyperkalemia, a mild non-anion gap metabolic acidosis, and elevated BUN and creatinine levels.

Treatment involves replacement of corticosteroids and mineralocorticoids. The normal adrenal gland output of cortisol is approximately 250 - 300 mg in 24 hours; this amount of hydrocortisone in soluble form (hydrocortisone sodium succinate or phosphate) should be given, preferably by continuous infusion.

In patients in acute adrenal crisis, IV access should be established urgently, and an infusion of isotonic sodium chloride solution should be started to restore volume deficit and correct hypotension. Some patients may require glucose supplementation.

The drugs that are effective in the treatment of hyperprolactinemia are dopamine agonists; they are the primary physiologic inhibitors of prolactin secretion. Bromocriptine is generally considered to be the agent of choice in the treatment of prolactinoma.

Insulin aspart is not appropriate, as the patient is euglycemic; her urinalysis does not reveal any evidence of ketoacidosis.

Metyrapone, along with ketoconazole, mitotane, cabergoline, and pasireotide, are medications useful in reducing ACTH or cortisol levels in patients with Cushing's syndrome.

Somatostatin and dopamine analogues and growth hormone (GH) receptor antagonists are the mainstays of medical treatment for GH excess syndromes (e.g., acromegaly and gigantism). They are generally used when primary surgery fails to induce complete remission. The most extensively studied and used somatostatin analogue, octreotide, binds to the somatostatin receptor; this inhibits GH secretion.
HHS
Explanation
The correct answer is a hyperglycemic hyperosmolar state (HHS). Most commonly seen in the elderly with type II diabetes mellitus, it is typically preceded by a few weeks of polyuria, weight loss, fatigue, and poor oral intake; this results in a change in mental status that can progress from confusion to lethargy, stupor, and coma. It is associated with dehydration and hyperosmolality that presents on physical examination with hypotension and tachycardia. It is usually precipitated by a serious infection (sepsis or pneumonia, which is most likely the case with this patient) or acute illness (stroke or myocardial infarction) in the postoperative period, or it is due to noncompliance.

Lactic acidosis is an accumulation of lactate due to excess formation and decreased utilization. Although an increase in lactic acid may occur in HHS, it is not the cause of this patient's condition. It may be seen in patients with type II diabetes treated with glucophage (metformin) in renal insufficiency or when taken during periods of illness, when bedridden, or in conjunction with intravenous radiographic contrast. It is the most common cause of metabolic acidosis in hospitalized patients; it occurs with excess production (with shock due to poor perfusion), poor utilization (hepatocellular dysfunction), or decreased clearance of lactate (cirrhosis). The metabolic acidosis is accompanied by a characteristic, compensatory hyperpnea with long, deep breaths, which this patient does not exhibit.

HHS results in a prerenal azotemia or acute renal failure, which is also a metabolic acidosis, but renal failure is not the underlying cause of this patient's condition. The fact that the patient has had polyuria over the past 2 weeks makes chronic renal failure unlikely.

Hypoglycemia has an acute onset when blood glucose is <70 mg/dL, which triggers secretion of counter-regulatory hormones (glucagon, epinephrine, cortisol) and growth hormone to raise blood glucose levels. This response produces adrenergic symptoms such as palpitations, tremor, anxiety, hunger, or nausea. A blood glucose decrease to <45 - 50 mg/dL will result in neuroglycopenia, with symptoms of weakness, confusion, and combativeness, and if untreated, it may result in seizure, coma, or death. This patient had an insidious onset of symptoms that signify hyperglycemia, not hypoglycemia.

Diabetic ketoacidosis is seen primarily in type I diabetics, and it is associated with nausea, vomiting, abdominal pain, acetone-odor breath, and Kussmaul breathing.
Lisinopril
Explanation
Lisinopril, an ACE Inhibitor, should help decrease albuminuria, prevent progression of diabetic kidney disease from micro to macroalbuminuria, and prevent a decline in glomerular filtration rate. This class of medications has been studied extensively for these purposes.

Angiotensin II receptor blockers (e.g., irbesartan) may also reduce urinary albumin to normal levels. Monotherapy with either of these classes of medications should be attempted first in patients with microalbuminuria. This will test tolerance, effectiveness, and adverse reaction such as hyperkalemia.

For patients with greater degrees of albuminuria (e.g., 1 g/day), poor response to monotherapy and blood pressure control, and no hyperkalemia associated with therapy, combination therapy should be considered. Combination therapy with both ACE inhibitors (e.g., lisinopril) and angiotensin II receptor blockers (e.g., irbesartan) is used to treat both diabetic and non-diabetic kidney disease. These medications act on different parts of the renin angiotensin system. In combination, irbesartan could block the effect of angiotensin produced by non-ACE pathways and lisinopril could block the production of angiotensin stimulated by irbesartan in a negative feedback system; however, combination therapy is usually preceded by monotherapy.

Although combination therapy is currently being used in both diabetic and non-diabetic kidney disease, this therapy still being researched. It is unknown whether monotherapy alone is sufficient. It does not appear to be sufficient in all patients, particularly those with persistent micro and macroalbuminuria despite monotherapy.

Sodium bicarbonate is used to treat the metabolic acidosis that commonly occurs secondary to chronic kidney disease. Diseased nephrons eliminate acids poorly, allowing them to build up in the blood stream. Sodium bicarbonate buffers these acids. Sodium bicarbonate is not known to significantly alter progression of proteinuria or decline in glomerular filtration rate.

Potassium chloride is a mineral used in the management of hypokalemia. We have no knowledge of hypokalemia in this patient and no indication to use potassium supplements. Potassium is not known to alter the progression of diabetic nephropathy. In fact, this woman is more likely to be hyperkalemic due to her diabetes, which can cause hyporeninism, hypoaldosteronism, and hyperkalemia. Giving potassium to patients already at risk for hyperkalemia is not advised, as hyperkalemia may provoke cardiac arrhythmias.

Calcium carbonate and calcium citrate are used to treat the hyperphosphatemia found commonly in patients with chronic kidney disease. They will not alter the progression of diabetic proteinuria.
A 42-year-old man presents with fatigue, polyuria, and polydipsia for the past 2 - 3 months. He has a history of hypertension and obesity. He is on 10 mg of amlodipine daily and 75 mg of aspirin daily. His family history is significant for diabetes mellitus in the patient's mother and 2 siblings. On exam, the patient is afebrile; he has a blood pressure of 130/80 mm Hg; he has a weight of 220 lbs, and his height is 66 inches. He has no pallor, icterus, or lymphadenopathy. Lungs are clear to auscultation, and heart sounds are regular. The abdomen is normal, and there is minimal pitting pedal edema. Initial fundus exam is normal. Tests are done, including fasting blood glucose on 2 different days, a basic metabolic panel, and lipid profile. Fasting blood glucose was 136 mg/dL on the 1st day and 140 mg/dL on the 2nd. He is diagnosed with type II diabetes mellitus.



Question
What is the best strategy for treatment of this patient?

Answer Choices
1 Diet control, weight loss, and exercise for 6 - 12 months; then, follow up tests should be performed for further treatment
2 Diet, weight loss, and exercise indefinitely if symptoms resolve
3 Oral hypoglycemic therapy with a sulfonylurea; tests should be repeated every 3 months, and a 2nd agent should be added if fasting blood sugar still above 140 mg/dL
4 Diet, weight loss, exercise, and monotherapy with metformin for 6 months, followed by repeat tests and adjustment of medication dose or addition of sulfonylurea
5 Diet, weight loss, and exercise for 4 - 6 weeks; then, if fasting blood sugar level remains above 126 mg/dL, add metformin
Diet, weight loss, and exercise for 4 - 6 weeks; then, if fasting blood sugar level remains above 126 mg/dL, add metformin
Explanation
A newly diagnosed patient with type II diabetes mellitus should be given a trial of therapeutic lifestyle changes with strict diet control, weight loss, and a moderately strenuous exercise regimen for 4 - 6 weeks. Afterwards, if the fasting blood sugar level is above 126 mg/dL, metformin should be added. Dietary modifications include low-calorie and low-fat diet with high complex carbohydrates. Some patients with mild diabetes may remain well controlled for a long period of time, but may eventually need medical treatment. Most patients need treatment sooner.

Metformin acts by decreasing hepatic gluconeogenesis and increasing peripheral utilization of glucose. It is the drug of choice in type II diabetics who are overweight, since it causes mild to moderate decrease in weight. It is also quite effective in non-obese patients. The common side effects include abdominal pain, diarrhea, a metallic taste in the mouth, nausea, and anorexia. Lactic acidosis is a serious side effect. The contraindications for use of metformin include prior history of lactic acidosis, renal insufficiency with creatinine of 1.5 mg/dL, alcoholism, hepatic insufficiency, sepsis and other severe infections, heart failure, hypoxia and respiratory depression, and concurrent or anticipated use of radiographic material.

In normal weight patients, sulfonylureas or biguanides are used. The dose may be increased every 4 - 8 weeks until blood sugar is controlled and hemoglobin A1C has decreased, with a goal of 7.0. Lifestyle changes should be continued for life.
Hypercortisolism
Explanation
This patient likely is suffering from Cushing syndrome, also known as hypercortisolism. Consequences of excessive levels of circulating cortisol, no matter the etiology, will lead to signs and symptoms such as central obesity, thin extremities, a moon face, a buffalo hump, supraclavicular fat pads, protuberant abdomen, and complaints of oligomenorrhea, amenorrhea, or possibly erectile dysfunction in men. Backaches, headaches, hypertension, acne, purple striae, and impaired wound healing may also be found in these patients.

Diabetes type 2 is caused by insulin resistance to circulating endogenous insulin in tissues. Eventually insulin is unable to be produced by the pancreatic islet cells, and an exogenous supply is required to prevent significant hyperglycemia and its related co-morbidities. Features of these patients include central obesity (specifically visceral obesity) with less fat noted on extremities. Patients will have a history or evidence of acanthosis nigricans, eruptive xanthomas on flexor surfaces, skin tags, chronic skin infections, frequent candidal vulvovaginitis in women, and erectile dysfunction or balanoposthitis in men.

Hypothyroidism and hyperthyroidism both are related to dysfunction of the thyroid gland; hypothyroidism is due to failure of the thyroid gland itself or deficient supply of pituitary TSH (thyroid stimulating hormone). Symptoms exhibited with hypothyroidism are weight gain, fatigue, lethargy, depression, weakness, menses irregularities, athralgias, muscle cramps, cold intolerance, dry skin, and constipation; signs present may include thinning hair, brittle nails, bradycardia, or even peripheral edema. Hyperthyroidism is the disease state wherein there is an excessive serum level of T3 and/or T4 along with suppressed TSH levels. Signs and symptoms may include: restlessness, nervousness, heat intolerance, increased sweating, weight loss, palpitations, atrial fibrillation, exophthalmos, or even pretibial myxedema, depending on the severity.

Diabetes insipidus (DI) is antidiuretic hormone deficiency. Signs and symptoms of DI include an extreme, unquenchable thirst with a very specific craving for ice water. Patients also will have significant polyuria or hypernatremia.
A 43-year-old Caucasian woman presents for evaluation of multiple concerns, including: a 6-month history of menstrual irregularities; weight gain with increased abdominal girth; easy bruising without a history of trauma; new "stretch marks" on her torso; mood swings; decreased libido, and weakness in her arms and legs. She had previously regular menses, a bilateral tubal ligation (BTL), and she reports multiple negative home pregnancy tests. She denies hot flashes, night sweats, and frank depression. She denies any health changes, medications, or stressors in relation to these changes. The patient is frustrated that her health fair labs (which include complete blood count, complete metabolic panel, lipid panel and thyroid stimulating hormone) were all normal, and they do not explain her symptoms.

Her past medical history is unremarkable, with no chronic conditions and no medication use; her only surgery was the BTL. She lives with her husband and 3 children. She works in retail, and she walks for exercise. She denies use of tobacco, alcohol, and drugs.

Her blood pressure is 154/92. Chart review demonstrates weight gain of 15 pounds over 6 months, with normal blood pressures in the past.

On physical exam, you observe an overweight woman with an especially rounded, full face. She has a fatty fullness to her neck and some central obesity, but her arms show some muscle wasting. Purple striae are noted on her torso. Her skin also appears thinned, with multiple bruises. Hirsutism is observed on the patient's chin, abdomen, and breasts. The remainder of her exam is unremarkable.



Question
What would best explain the pathophysiologic basis for this patient's condition?

Answer Choices
1 Autoimmune destruction of adrenal glands, causing decreased cortisol production
2 Exogenous administration of corticosteroids, causing increased adrenal production of cortisol
3 Hypoplastic adrenal cortex, causing low serum levels of cortisol
4 Increased adrenocorticotropic hormone (ACTH) secretion from pituitary, causing increased adrenal production of cortisol
5 Low adrenal production of cortisol, causing increased renal retention of cortisol
Hashimoto's Thyroiditis
The presence of antithyroid antibodies and the typical histology points to a diagnosis of Hashimoto's thyroiditis (chronic lymphocytic thyroiditis). It is the most common form of thyroiditis, and most common cause of hypothyroidism in the US. This condition is characterized by thyroid cell destruction by various antibody-mediated immune processes. The gland appears diffusely enlarged and firm. Increased circulating levels of antithyroid peroxidase or anti-thyroglobulin antibodies is a diagnostic feature.

Hashimoto's thyroiditis is a histological diagnosis characterized by infiltration of lymphocyte and plasma cells, reduced size of the thyroid follicles containing sparse colloid, and fibrosis along with presence of follicle with oxyphilic change called Hurthle cells.

The image shows replacement of thyroid follicles by lymphoplasmacytic infiltrate with germinal centers (indicated by arrows).

Riedel's thyroiditis is characterized by dense fibrosis, which results in a stony hard enlargement of the thyroid gland. It is the rarest form of thyroiditis. Histological features of Riedel's thyroiditis include a fibro-inflammatory process involving a portion or the entire thyroid gland and the presence of fibrotic extension into the adjacent structures beyond the thyroid capsule.

Subacute painless thyroiditis is a self-limiting disease process having triphasic clinical presentation of hyperthyroidism, hypothyroidism, and return to euthyroid state. Thyroid biopsy shows presence of lymphocytic infiltration.

Suppurative thyroiditis is rare and associated with severe anterior neck pain, tenderness, and redness in the region. It is an acute thyroiditis characterized by high fever and a swollen and tender thyroid gland. Lab findings include leukocytosis and increased erythrocyte sedimentation rate (ESR).

De Quervain's thyroiditis, also called subacute granulomatous thyroiditis, is a painful enlargement of the thyroid gland. It is believed to be caused by viral infection or a post-viral inflammatory response. The histological finding in De Quervain's thyroiditis includes the presence of multinucleated giant cell granulomas.
Blood Glucose Level
Explanation
Diabetes mellitus (DM) should be excluded first in all patients with polyuria. Therefore, checking blood glucose level is the next best step. Should DM be ruled out, you should then determine the correct etiology of the patient's symptoms.

Diabetes insipidus (DI) is also on the differential diagnosis. DI is caused by either a deficiency of arginine vasopressin (central DI) or an insensitivity to its effects at the level of the kidney (nephrogenic DI). Symptoms include polyuria, polydipsia, and decreased urine specific gravity.

Causes: 1) Central; due to tumor, anoxia, or hemorrhage. 2) Nephrogenic; due to the effect of central drugs, of which lithium is a well-known cause.

Differential diagnoses: 1) Diabetes mellitus. 2) Psychogenic polydipsia

Workup:

1) First, exclude DM by random blood sugar; then, psychogenic polydipsia should be excluded by water deprivation test (in this case scenario, the patient did it himself).
2) Second, do a desmopressin test to differentiate nephrogenic from central DI.
3) If it is positive, then perform MRI to exclude brain tumors.

Treatment: 1) In mild cases, adequate hydration is enough. 2) For central DI, give desmopressin. 3) In cases of psychogenic polydipsia, psychiatric consultation is needed.

If drug induced, stop offending drug.

The DDAVP test is performed to differentiate central from nephrogenic DI. Brain MRI can be used to detect pituitary tumors that may cause diabetes insipidus. Urine osmolarity is significantly reduced in diabetes insipidus and may be helpful in determining a diagnosis. Although all of these has a role in diagnosis, they are not the best answer to the question.
DI
Explanation
This patient is suffering from diabetes insipidus (DI). Characteristics of this disease process include an increase in thirst and the passage of large quantities of urine. The underlying pathologic feature of DI is a deficiency of vasopressin or a resistance to available vasopressin. There are a multitude of disease states that lead to DI and the patient above is most likely suffering from an acquired form of vasopressin-resistant diabetes insipidus. Disease states that lead to this form of DI can include pyelonephritis, renal amyloidosis, potassium depletion, Sj?gren's syndrome, use of some medications, and, in the patient's case, the use of lithium. Chronic use of lithium can lead to lithium toxicity and manifests as described in the patient scenario. This is one of the more common causes of DI in adult patients.

Hypothyroidism is much lower on the differential due to the signs and symptoms being inconsistent. Findings such as weakness, fatigue, cold intolerance, constipation, weight changes, depression, or menstrual abnormalities would be some of the multiple features evident in patients with hypothyroidism.

Hypoparathyroidism is also not as likely. Signs and symptoms of the acute phase of this disease include tetany, muscle cramps, irritability, altered mental status, and convulsions; a tingling sensation around the circumoral area, hands, and feet is almost always present.

Cushing's disease is due to manifestations of hypercortisolism secondary to adrenocorticotropic hormone (ACTH) hypersecretion by the pituitary gland. Some features include but are not limited to: central obesity, apparent moon face or buffalo hump, purple striae, muscle wasting, hirsutism, psychological changes, hypertension, weakness, headache, backache, or poor wound healing. None of the signs or symptoms listed matches the patient's history above.

Diabetes mellitus (DM) may also be considered in this patient scenario given the symptoms of polydipsia and polyuria described, as well as the strong family history evident. The main cause of this type of diabetes is that patients develop increased tissue insulin insensitivity, also termed insulin resistance. Some key components of the patient's history are not evident in diabetes mellitus. Nocturnal enuresis is not usually a significant chief complaint in patients with DM, although patients with DM may have complaints of polyuria, polydipsia, weakness, fatigue, blurred vision, vulvovaginitis, peripheral neuropathy, or even potentially be asymptomatic.
NSAIDS
Explanation
The clinical picture is suggestive of subacute thyroiditis, also called DeQuervain's thyroiditis. The etiology is unclear, but it is usually a result of viral infection with coxackie, mumps, and adenovirus, among others. NSAIDs are the drug of choice, with steroids being a backup drug for severe cases.

The pathophysiology involves inflammation of the thyroid gland with release of colloid and preformed thyroid hormone. Histology shows infiltration of the gland with mononuclear cells and non-caseous granulomas. Due to destruction of the follicular cells, colloid and thyroid hormones are released into the general circulation, resulting in hyperthyroidism. The hyperthyroid phase lasts as long as the preformed colloid is release. A transient hypothyroid phase while the follicular cells regenerate commonly follows the depletion of colloid.

The hallmark of the inflammation is pain, usually described by the patient as being vaguely in the front of the neck and presenting while swallowing, chewing, or radiating to the jaw. Hyperthyroid symptoms commonly manifest as palpitations, sweating, fatigue, weight loss, and diarrhea. Examination typically reveals tenderness over the thyroid gland, which may sometimes be severe.

Lab investigations show an elevated ESR, which is evidence of inflammation. Thyroid hormone levels reflect the hyper or hypothyroid phase of the illness. Thyroglobulin levels may be elevated due to the release of colloid. Radio iodine uptake studies show diffusely reduced uptake due to the destruction of cells. This is in direct contrast to Grave's disease, where there is diffusely increased uptake. NSAIDs are usually sufficient for treatment. Rarely steroids are required for severe disease.

Propylthiouracil is incorrect. The hyperthyroidism in thyroiditis is due to inflammation and destruction of cells with the release of preformed thyroid hormones, with an eventual return to normal. Administering anti-thyroid medication is unnecessary.

Radioiodine ablation is incorrect, as subacute thyroiditis is a reversible condition, with thyroid function eventually coming back to normal.

High dose prednisone is incorrect. It may be used in severe thyroiditis not responding to NSAIDs, but should be avoided as a first line medication due to the associated side effects.

Levothyroixine is incorrect. This patient is hyperthyroid at present, and thyroxine would exacerbate the problem.
Cushings Syndrome
Explanation
This patient likely is suffering from Cushing syndrome, which is also known as hypercortisolism. Consequences of excessive levels of circulating cortisol, no matter the etiology, will lead to signs and symptoms such as central obesity, thin extremities, a moon face, a buffalo hump, supraclavicular fat pads, protuberant abdomen, oligomenorrhea, and amenorrhea; in men, erectile dysfunction is sometimes seen. Backaches, headaches, hypertension, acne, purple striae, and impaired wound healing may also be found in these patients.

Diabetes type II is caused by insulin resistance in tissues to circulating endogenous insulin. Eventually, insulin is unable to be produced by the pancreatic islet cells, and an exogenous supply is required to prevent significant hyperglycemia and its related co-morbidities. Features of these patients include central obesity (specifically visceral obesity), with less fat noted on extremities. Patients will have a history or evidence of acanthosis nigricans, eruptive xanthomas on flexor surfaces, skin tags, chronic skin infections, frequent candidal vulvovaginitis in women, and erectile dysfunction or balanoposthitis in men.

Both hypothyroidism and hyperthyroidism are related to dysfunction of the thyroid gland; hypothyroidism is due to failure of the thyroid gland itself or deficient supply of pituitary TSH (thyroid stimulating hormone). Symptoms characteristic of hypothyroidism include weight gain, fatigue, lethargy, depression, weakness, menses irregularities, athralgias, muscle cramps, cold intolerance, dry skin, and constipation; other signs may include thinning hair, brittle nails, bradycardia, or even peripheral edema. Hyperthyroidism is the disease state in which there is an excessive serum level of T3 and or T4 along with suppressed TSH levels. Signs and symptoms may include restlessness, nervousness, heat intolerance, increased sweating, weight loss, palpitations, atrial fibrillation, exophthalmos, or (depending on the severity) even pretibial myxedema.

Diabetes insipidus (DI) is an antidiuretic hormone deficiency. Signs and symptoms of DI include an extreme, unquenchable thirst with a very specific craving for ice water. Patients also will have significant polyuria or hypernatremia.
Lithium
Explanation
Lithium, used in the treatment of bipolar disorder, is a common cause of diabetes insipidus. It is freely filtered through the glomerulus and reabsorbed in the proximal tubule along with sodium and water. Even small doses of lithium may cause diabetes insipidus. Lithium can also make the distal renal tubules resistant to the action of vasopressin. This patient had recently started this medication, which resulted in his new symptoms.

Carbamazepine, amitriptyline, and valproic acid do not cause diabetes insipidus. Analogues of vasopressin are used to treat diabetes insipidus.

Diabetes Insipidus (DI) exists in 1 of 2 forms: central and nephrogenic. In central diabetes insipidus, there is a decrease in the secretion of antidiuretic hormone (ADH). This results in polyuria and polydipsia and the patient has a diminished ability to concentrate urine. Decreased or deficient ADH can be caused by a defect in the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, or the supraoptico-hypophyseal tract.

Nephrogenic DI is defined as a decrease in the ability to concentrate urine due to a resistance to ADH on the kidney. It can be seen in chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, and tubulointerstitial disease. There is a hereditary form of nephrogenic DI that is rare and is transmitted as an X-linked genetic defect of the V2 receptor gene.

ADH's main target is the kidney. It causes an alteration of permeability to water of the collecting tubules in the kidney's medulla and cortex. Water is reabsorbed by osmotic equilibration and is put back into the bloodstream. The actions of ADH are mediated through at least 2 receptors. The first is known as V1. V1 mediates vasoconstriction and enhances the release of corticotrophin. It also takes part in the synthesis of renal prostaglandins. The second one, known as V2, is a mediator of the antidiuretic response.

The diagnosis of DI is usually made clinically. If a patient is able to match fluid loss with adequate fluid intake, their condition may appear to be otherwise normal. If they cannot keep up with fluid demand, they will begin to show signs of dehydration (sunken eyes, dry skin and mucous membranes, fever, tachycardia, unintentional weight loss). Other symptoms include headache, fatigue, muscle aches and irritability.

A urine specific gravity of 1.005 or less and a urine osmolality less than 200 mOsm/kg is the hallmark of DI. Random plasma osmolality generally is greater than 287mOsm/kg. It is important to rule out other causes such as diabetes mellitus. One way to do this is to use the water deprivation test. A patient is monitored, and his/her water intake is withheld. The patient's weight and urine osmolality are measured on an hourly basis. If two urine osmolality readings are less than or equal to 30 mOsm on two consecutive readings, or if the person's weight decreases by 3% or more, then 5 units of vasopressin is given and another urine sample is checked after an hour. A normal reading will show a urine osmolality that is 2 to 4 times greater than the plasma osmolality. In patients with central DI, urine osmolality can increase by 50% or more. ADH levels will be extremely low in central DI. If a patient has nephrogenic DI, their response to the test will be an ADH level that is either normal or increased. There will be no response to the ADH by the kidney.

The disease is very uncommon in the U.S., and men and women are affected approximately equally. The most common causes are head trauma and surgery.

There is a genetic form of DI that is rare and is inherited in an autosomal dominant pattern. It is caused by a mutation in the AVP-neurophysin gene.

Medications used to treat DI include vasopressin analogues in either oral, nasal, or subcutaneous forms. Other medications used include indomethacin, carbamazepine, thiazide diuretics, and chlorpropamide.
Explanation
The patient should increase consumption of fish oils.

Most patients with high cholesterol levels present with no specific symptoms or signs, although this is a significant contributor to the number one killer of adults in the United States, which is cardiovascular disease. There are a multitude of modifiable as well as non-modifiable risk factors present that contribute to overall cholesterol levels in each patient. If a patient has any abnormal cholesterol levels, the first component of any treatment is appropriate patient education regarding lifestyle modifications. Modifiable risk factors a patient should be instructed to initiate include the concept of moderation of energy intake and specifically limiting the energy intake from animal fats, which are also known as saturated fats. Body weight control is critical and regular aerobic activity should be encouraged in these patients. Patients should be instructed to avoid high-carbohydrate and refined carbohydrates. Increasing consumption of unsaturated fats is recommended; this has been shown to specifically lower triglycerides. Fish oils have also been found to contain the essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both with known effectiveness at also lowering triglyceride levels.

Limiting consumption of alcohol as well as smoking cessation are also critical components of lifestyle modification initiation. If an earnest attempt at lifestyle modification is taken and the efforts fail to bring cholesterol levels to normal ranges, then pharmaceutical intervention should be initiated.
Somoygi
Explanation
The correct answer is that the patient is most likely experiencing the Somogyi effect. The Somogyi effect begins with an episode of nocturnal hypoglycemia; this triggers the body's counter-regulatory response, secreting glucagon, epinephrine, and cortisol plus growth hormone to raise the blood sugar, resulting in elevated morning levels or rebound hyperglycemia. The nocturnal hypoglycemia is due to hyperinsulinemia as a result of insulin therapy in conjunction with decreased evening caloric intake or extra calories utilized for activity, especially in the evening hours. The symptoms of nocturnal hypoglycemia (restlessness, profuse sweating, and nightmares) occur most often when the patient is asleep; it is possible that only a parent or partner may notice them. Patients also tend to awaken with a severe morning headache. Adrenergic symptoms of hypoglycemia, such as palpitations, tremor, anxiety, hunger, and nausea, are the result of the counter-regulatory hormones secreted at blood glucose levels < 70 mg/dL; they may be noticeable by the patient. Neuroglycopenia, with symptoms of weakness, confusion, and combativeness, occurs if the blood glucose falls below 45 - 50 mg/dL; if untreated, they may result in seizure, coma, or death. Checking blood sugars at 3:00 am or continuous glucose monitoring are useful to detect nocturnal hypoglycemia. This patient would benefit from correcting the nocturnal hyperinsulinemia with a bedtime snack, limiting evening exercise, decreasing the dinner dose of aspart, or decreasing the daily dose of glargine if his basal blood sugars, fasting, and pre-meal are low.

The Dawn phenomenon also results in morning hyperglycemia, but this is due to the physiologic secretion of growth hormone in the early morning hours, which produces insulin resistance. In this case, there is insufficient insulin to overcome this inherent insulin resistance, so patients arise with elevated morning blood sugars. This can also be documented by checking 3:00 am blood sugars or continuous glucose monitoring, and it is corrected by adding insulin to the evening or nighttime regimen.

The onset of puberty would result in accelerated secretion of growth hormone, resulting in morning hyperglycemia, but it would not explain the symptoms of nocturnal hypoglycemia.

Tonic seizures occur most frequently in childhood and during sleep. Although his mother did not specifically note any tonic (sustained) or clonic (rapid contraction/relaxation) activity, other forms of seizures can present with night terrors. Likewise, untreated hypoglycemia can result in seizures. Although a seizure disorder would be included in the differential diagnosis, it would not explain the recent onset of morning hyperglycemia.

The symptoms of diabetic ketoacidosis include nausea, vomiting, abdominal pain, polyuria, acetone-odor breath, and Kussmaul breathing.
Explanation
Subacute lymphocytic thyroiditis, or painless thyroiditis, is an uncommon cause of hyperthyroidism. It is considered a variant of Hashimoto's thyroiditis, as this disorder is also characterized by the presence of autoantibodies to thyroid globulin and thyroid peroxidase. The symptoms develop over a period of 1 to 2 weeks and last from 2 - 8 weeks before subsiding. Infiltrative ophthalmopathy and other features of Graves' disease are absent. In addition, even though the serum T3 and T4 levels are increased and TSH levels are decreased during the episode of hyperthyroidism, the radioiodine uptake is decreased.

Graves' disease, also known as diffuse toxic goiter or Basedow's disease, is characterized by hyperthyroidism, diffuse thyroid enlargement, and infiltrative ophthalmopathy with resultant exophthalmos and infiltrative dermopathy. It is an autoimmune disease and shows elevated levels of T3 and T4 and depressed levels of TSH. However, the radioiodine uptake is increased, and the thyroid scan shows a diffuse uptake of iodine. Refer to the table for additional information.

Hashimoto's thyroiditis (also known as autoimmune thyroiditis, diffuse lymphocytic thyroiditis, struma lymphomatosa, or goitrous autoimmune thyroiditis) is characterized by 3 main features:

Diffuse goitrous enlargement of the thyroid
Lymphocytic infiltration of the thyroid gland
Occurrence of thyroid autoantibodies
Juvenile lymphocytic thyroiditis, a variant of Hashimoto's thyroiditis, is also known as lymphocytic thyroiditis of childhood and adolescence. It occurs mainly in children and young females and is characterized by a mild enlargement of the thyroid and a lower level of autoantibodies compared to Hashimoto's thyroiditis. The patient is mildly hypothyroid or euthyroid and is symptomless.

Atrophic thyroiditis is also a variant of Hashimoto's thyroiditis, and it is also known as idiopathic myxedema or spontaneous hypothyroidism. Instead of enlargement, there is diminution in size of the thyroid, and it is characterized by the presence of autoantibodies.
An HDL of <40; Age (men >45yrs, women >55yrs)
Explanation
The NCEP/ATEP has set forth explicit Risk Factors as well as specific lipid goals/classifications that clearly address what parameters dictate the initiation or cessation of pharmacotherapy. This question illustrates that, in patients with a major risk factor (CHD/Diabetes), the goal of drug therapy is to keep the level of LDL lipids <100. Likewise, drug therapy should be started when the LDL is >130.

An HDL of <40 is undesirable, and so is the age factor (>45yrs for men and >55 years for women). This case illustrates the rationale of pharmacotherapy in the presence of 2 or more risk factors. The specific LDL lipid level should be identified to guide the initiation and goal of pharmacotherapy. Drug therapy for patients with 2+ risk factors should be started when the LDL is >130. The LDL goal is <130.

A patient with a TC of <200 is already in the desirable range and would not need drug therapy based on lipid classification alone. It should be noted that the TC is only a general marker; therefore, the individual lipid molecules need to be identified via a lipid panel/profile. The presence of 0-1 risk factors (HBP) mandates that drug therapy should be started when the LDL is >190; the goal of therapy is an LDL <160. Once the LDL level is identified, then the decision whether or not to initiate drug therapy can be discussed.

An HDL of >60 is very desirable. There is a direct correlation between the level of HDL and the absence of coronary plaque. It should be noted that the LDL level should still be identified in order to ascertain the true lipid picture. Cigarette smoking is only 1 risk factor; therefore, drug therapy should be initiated when the LDL is >190. The goal of therapy is an LDL level of <160. Once the LDL lipid level is identified, the option of drug therapy can be discussed.

The VLDL lipid molecule can be a separate risk factor and is usually elevated along with TG. The VLDL level becomes important (VLDL > 200 - 300) when it is accompanied by elevated TG (200-499). As in the above explanations, the LDL lipid level should be identified due to the direct correlation between LDL and CHD. A major risk factor, such as diabetes, mandates that drug therapy be initiated when the LDL is >130. The LDL goal is <100. Once the LDL level is lowered to an acceptable range, the elevated VLDL and TG (especially if TG is >500) should be addressed by initiating either a combination of diet and exercise (will lower VLDL) and/or drug therapy. The Statins have a modest effect on VLDL/TG, whereas niacin and gemfibrozil have been shown to dramatically reduce these lipid levels.
Graves' Disease
Explanation
The correct answer is Graves' disease, which is identified on Radioactive I 131 Uptake (RAIU) with an increased amount of iodine uptake consistent with hyperthyroidism and a scan that reveals a diffuse, uniform pattern throughout the gland. This is due to the autoimmune process of Graves' disease, in which circulating Thyroid Stimulating Immunoglobulins affect the entire gland. On physical exam, the gland will be firm and diffusely enlarged, which explains the diffuse uptake of iodine throughout the gland in the typical uniform pattern on RAIU and scan.

A toxic thyroid adenoma and toxic multinodular goiter (TMNG) are also etiologies of thyrotoxicosis, and they can present with signs, symptoms, and laboratory values consistent with hyperthyroidism. On thyroid exam, a toxic adenoma is often a palpable thyroid nodule; however, a multinodular goiter will present, just as the name implies, with many fibrotic areas in an enlarged gland. Likewise, a toxic adenoma and TMNG may have an increased uptake on RAIU consistent with thyrotoxicosis, but they are distinguished from Graves' disease on the subsequent scan. A toxic adenoma reveals 1 area of increased uptake, which is localized to the adenoma and is often described as a "hot nodule," indicating the adenoma is hyperfunctioning. TMNG will reveal a heterogeneous pattern of radioactive iodine uptake localized to multiple hyperfunctioning nodules of various sizes throughout the gland.

Patients with thyroid cancer most often present asymptomatically, with or without a palpable thyroid nodule and normal thyroid function studies. There is typically a normal RAIU uptake, but the scan reveals an area of decreased iodine uptake localized to the site of the thyroid cancer, which is often referred to as a "cold nodule."

Thyroiditis usually occurs during or after a respiratory illness, and it presents acutely with symptomatic pain in the gland; the pain is often associated with fever, elevated WBCs, and sedimentation rate. Changes in serum thyroid hormone levels will depend upon the phase of the disease. Early in the disease, thyroid function is normal; then, hyperthyroidism develops as thyroid hormone is released from the gland after the initial insult. The pituitary gland responds to the excess circulating thyroid hormone by decreasing TSH production. Subsequently, the patient will progress from hyperthyroidism to euthyroidism to hypothyroidism. As thyroid hormone levels drop, the pituitary will respond by increasing TSH production, and the patient will enter the recovery phase, resuming normal thyroid function. RAIU will reveal a normal or low iodine uptake because there is no increased thyroid tissue activity and there is often no pattern visible on scan due to the limited uptake.
A 43-year-old Caucasian woman presents for evaluation of multiple concerns, including: a 6-month history of menstrual irregularities; weight gain with increased abdominal girth; easy bruising without a history of trauma; new "stretch marks" on her torso; mood swings; decreased libido, and weakness in her arms and legs. She had previously regular menses, a bilateral tubal ligation (BTL), and she reports multiple negative home pregnancy tests. She denies hot flashes, night sweats, and frank depression. She denies any health changes, medications, or stressors in relation to these changes. The patient is frustrated that her health fair labs (which include complete blood count, complete metabolic panel, lipid panel and thyroid stimulating hormone) were all normal, and they do not explain her symptoms.

Her past medical history is unremarkable, with no chronic conditions and no medication use; her only surgery was the BTL. She lives with her husband and 3 children. She works in retail, and she walks for exercise. She denies use of tobacco, alcohol, and drugs.

Her blood pressure is 154/92. Chart review demonstrates weight gain of 15 pounds over 6 months, with normal blood pressures in the past.

On physical exam, you observe an overweight woman with an especially rounded, full face. She has a fatty fullness to her neck and some central obesity, but her arms show some muscle wasting. Purple striae are noted on her torso. Her skin also appears thinned, with multiple bruises. Hirsutism is observed on the patient's chin, abdomen, and breasts. The remainder of her exam is unremarkable.



Question
What would best explain the pathophysiologic basis for this patient's condition?

Answer Choices
1 Autoimmune destruction of adrenal glands, causing decreased cortisol production
2 Exogenous administration of corticosteroids, causing increased adrenal production of cortisol
3 Hypoplastic adrenal cortex, causing low serum levels of cortisol
4 Increased adrenocorticotropic hormone (ACTH) secretion from pituitary, causing increased adrenal production of cortisol
5 Low adrenal production of cortisol, causing increased renal retention of cortisol
Increased adrenocorticotropic hormone (ACTH) secretion from pituitary, causing increased adrenal production of cortisol
Explanation
This patient presents with a multitude of signs and symptoms (weight gain, menstrual irregularity, mood swings, poor libido, moon facies, fat depositions, proximal limb weakness, central obesity, skin thinning, purple striae, and easy bruising) that support a diagnosis of Cushing syndrome. The most common cause of Cushing syndrome is considered iatrogenic, from administering exogenous steroids, such as prednisone. The next most common cause is known as Cushing disease and results from increased adrenocorticotropic hormone (ACTH) secretion from pituitary, causing increased adrenal production of cortisol. This patient should be evaluated with laboratory tests, and then imaging, to look for a pituitary adenoma.

Autoimmune destruction of adrenal glands, causing decreased cortisol production, is the most common mechanism for development of Addison's disease. Addison's disease also has multiple, somewhat nonspecific signs and symptoms, but they differ from those of excess cortisol production. A patient with Addison's may have fatigue, weakness, hypotension, hyperkalemia and hyponatremia, hyperpigmentation of the skin, anorexia, nausea, vomiting, diarrhea, and weight loss.

As indicated above, exogenous administration of corticosteroids is the most common cause of iatrogenic Cushing syndrome. However, the effect of administering corticosteroids is suppression of (not increased) adrenal cortisol secretion. This is also the rationale for tapering off prescribed corticosteroids, in order to allow the patient's natural adrenal production of cortisol to return to normal. Otherwise, an Addison's-type situation occurs with sudden discontinuation of high-dose steroids.

Hypoplastic adrenal cortices would be unable to produce normal cortisol levels, thus causing low serum cortisol levels. Congenital adrenal hypoplasia is another (less common) cause of Addison's disease.

Renal retention, or elimination, of cortisol is not a mechanism for controlling cortisol levels in the body. Instead, corticotropin-releasing hormone (CRH) from the hypothalamus and ACTH from the pituitary gland, and to a lesser degree, arginine vasopressin (AVP), regulate physiologic cortisol levels. It would be expected that when low adrenal production of cortisol occurs, there would be an increase in CRH and ACTH in order to stimulate more adrenal production of cortisol.
Peri-operative steroid coverage with hydrocortisone should be started 1 - 3 days prior to the planned surgery
The rationale for stress steroid coverage is that chronic corticosteroid therapy suppresses the hypothalamic-pituitary-adrenal (HPA) axis, although this has never been well-documented in studies. Patients who are not taking glucocorticoids activate HPA axis with surgery, trauma, and severe illness. Adults who do not experience stress secrete cortisol equivalent to 5 mg/day of prednisone or 20 mg hydrocortisone/day. Generally, the recommended dose has been 3 to 5 times the amount secreted daily, which is up to 200 - 400 mg/day of hydrocortisone. More recent studies suggest that lower doses may be used. Suggested lower doses for major surgery, such as cardiopulmonary bypass, are up to 100 - 150 mg/day hydrocortisone for 2 - 3 days, and 75 - 100 mg/day for moderate procedures, such as orthopedic surgery, for 1 - 2 days. Even when a patient has taken glucocorticoids in the past and has stopped, the HPA axis may recover quickly or not fully recover for 9 - 12 months.

Succinylcholine, a depolarizing agent, may induce increased muscle contractions and may cause rhabdomyolysis. With muscle breakdown, creatine phosphokinase, potassium, and myoglobin may be released. The large proteins of the myoglobin may cause renal damage. Elevated potassium levels may cause cardiac arrest. Both succinylcholine and inhalational anesthetics may cause a malignant hyperthermia-like response. High intracellular calcium levels lead to activation of actin and myosin fibers with continuous contractions of the muscles producing muscular rigidity and spasm. A hypermetabolic state occurs in the muscle cells resulting in increased oxygen consumption and metabolic acidosis. Respiratory acidosis may occur with elevated CO2 levels. As a result of the hypermetabolic state, hyperthermia occurs, along with tachycardia and possible cardiac arrhythmia. Nitrous oxide is a safe inhalational agent. Also safe are non-depolarizing muscle relaxants, including pancuronium, cisatracurium, vecuronium, rocuronium, atracurium, and mivacurium.

Echocardiography should be done pre-operatively in all patients with Duchenne muscular dystrophy. In the past, patients commonly died from respiratory problems. As care for these conditions has improved, dilated cardiomyopathy has become an increasingly common morbidity and cause of death in these patients. The time course for development of cardiomyopathy is not clearly defined. There may be limited ability to increase cardiac output, with stress resulting in impaired oxygen delivery. Clinical symptoms of cardiac dysfunction may be subtle, vague or unrecognized, as these children have limited physical activity. Scoliosis may limit the usefulness of echocardiography, making it difficult get appropriate windows. In addition, echocardiography may not detect the myocardium's ability to respond to stress. It has been suggested that pre-operative stress echocardiography may be a more reliable test. Intraoperative transesophageal echocardiography, pulmonary arterial catheterization, and pulse contour analysis (PCCO) may be of great benefit for intraoperative monitoring. There is evidence that specific dystrophin gene mutations may be predictive of cardiomyopathy, while other mutations may be protective or inhibitory toward its development1.

Forced vital capacity should be determined before surgery. There are no absolute contraindications to surgery based on pulmonary function. Good results have been reported in patients with FVC 20% of predicted, although best prognosis for recovery seems to be with FVC >40% predicted. Pre-operative sleep studies or nocturnal oximetry can be helpful if abnormal, noninvasive nighttime ventilation can be instituted prior to surgery.
Iodine deficiency
Explanation
In cases of iodine deficiency, patients can present with an anterior neck swelling that rises with deglutition. This is usually a colloid goiter, as the thyroid hypertrophies as it tries to concentrate iodide in itself. Though most of these patients are euthyroid, some may develop hypothyroidism. Cretinism can develop in infants as a result of iodine deficiency; impaired brain development and fetal growth can also develop. Causes include inadequate dietary intake. Dietary sources of iodine include iodized table salt, seafood, eggs, and dairy products.

In cases of zinc deficiency, patients can present with hypogeusia or decreased taste sensation, anorexia, delayed sexual maturation, night blindness, and hair loss. On examination, they have alopecia, growth retardation, delayed sexual maturation, and hypogonadism. Laboratory investigations may reveal hypospermia. Causes include malabsorption states, alcoholism, and prolonged parenteral nutrition. Dietary sources of zinc include beef, liver, eggs, and oysters.

Menkes syndrome is an inherited copper deficiency caused by mutations in an X-linked gene. It occurs in male infants and is characterized by intellectual disabilites, kinky hair, hypopigmentation, and vascular aneurysms. Laboratory investigations reveal hypocupremia and decreased circulating ceruloplasmin. Other causes of copper deficiency include severe malabsorption, infants with persistent diarrhea fed on milk diets, copper-free total parenteral nutrition, and excess intake of a zinc salt dietary supplements, which can interfere with copper absorption. Dietary sources of copper include organ meats, oysters, nuts, dried legumes, and whole grain cereals.

Patients with folic acid deficiency present with symptoms of anemia such as fatigue, weakness, and syncope. On examination, they are pale. Laboratory investigations reveal macrocytic red blood cells and hemoglobin less than 12 g/dl. Causes include malabsorption and inadequate intake by chronic alcoholics and malnourished individuals, as well as increased demand in pregnancy and chronic hemolytic anemias. Dietary sources of folic acid include green leafy vegetables, liver, and yeast.

Patients with a vitamin B12 (cobalamin deficiency) can present with symptoms and signs of anemia, such as fatigue, light-headedness, syncope, and pallor; there are also neurological signs and symptoms, such as ataxia, paraesthesias, and diminished proprioceptive and vibratory sensations in the lower limbs. Laboratory investigations reveal macrocytic red blood cells. Causes include pernicious anemia, blind loop syndrome, fish tapeworm infestation, and vegetarian diets. Dietary sources of vitamin B12 include liver, beef, eggs, and milk.
Pheochromocytoma
Explanation
Headache, palpitations, and diaphoresis are the classic triad of a pheochromocytoma crisis. These catecholamine-secreting tumors, most commonly found in young to mid-adult women, present with paroxysmal episodes in over 50% of patients. The episodes are of sudden onset, last minutes to hours, and they sometimes occur as a result of activity affecting the abdomen; often, they occur without a clear precipitating event. Hypertension with tachycardia occurs in most patients, presenting only during attacks in 40% of those patients, while the remaining 60% have sustained hypertension with half of those patients also experiencing hypertensive crises. In the absence of sustained hypertension or a paroxysmal episode, physical exam is often unremarkable. Diagnosis is made based on a 24-hour urine specimen for vanillylmandelic acid (VMA), metanephrines, and free catecholamines. Urine collection should occur when the patient is hypertensive or initiated at the time of a paroxysmal crisis.

Associated symptoms during a paroxysmal episode may include apprehension or a sense of doom suggesting an anxiety attack. Although anxiety attacks present as recurrent, unpredictable episodes of intense fear that can be associated with palpitations and sweating, they lack the malignant hypertensive response of a pheochromocytoma.

A pheochromocytoma crisis may precipitate chest pain with nausea, vomiting, pallor, and arrhythmias. The catecholamine surge, rather than coronary artery disease, may induce myocardial ischemia, resulting in angina and myocardial infarction.

Signs and symptoms of increased metabolic rate associated with a pheochromocytoma such as weight loss, palpitations, and sweating may also suggest hyperthyroidism. The most common cardiac manifestation in thyrotoxicosis is an arrhythmia, such as sinus tachycardia or atrial fibrillation in patients > 50 years of age, and not the malignant hypertension associated with a pheochromocytoma.

Renal artery stenosis presents as an abrupt onset of hypertension, malignant and/or refractory, typically associated with abdominal and/or flank bruits. When it occurs in younger women, it is most often the result of fibromuscular dysplasia of the arterial wall. When the onset occurs at > 50 years of age, it is most often the result of atherosclerotic plaques.
Increase the dose of Synthroid (levothyroxine)
Explanation
The correct choice is to increase the dose of Synthroid (levothyroxine) for the treatment of secondary hypothyroidism. TSH secretion is controlled by hypothalamic thyrotropin-releasing hormone (TRH) and negative feedback from circulating free thyroid hormones FT4 and FT3. It is the most important test in the diagnosis of thyroid disorders. However, in this patient (who previously underwent surgical resection of the pituitary), postoperative TSH secretion was found to be insufficient; this resulted in hypothyroidism secondary to pituitary dysfunction, thus requiring life-long thyroxine replacement. In patients with secondary hypothyroidism, the TSH levels remain low or inappropriately normal (for the circulating thyroid hormone levels), so the dosage of thyroxine is titrated to maintain circulating thyroid hormone levels within the normal range.

Since the patient has a low serum free T4, she is hypothyroid; therefore, it is inappropriate to decrease, discontinue, or continue her current dose of Synthroid.

Based upon her history, the low serum TSH is the result of surgical intervention, not indicative of hyperthyroidism, so Tapazole and an I131 uptake and scan are not indicated.

It would also be prudent to obtain past medical records, including post-operative and recent laboratory results, to ensure the remainder of the pituitary hormone levels are within normal limits. Levels that should be looked at include prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (HGH), and adrenocorticotropic hormone (ACTH).
Growth hormone does not activate its receptor
Explanation
Human growth hormone, also known as somatotropin, is a 191 amino acid polypeptide with a molecular weight of 22,000 and is the major hormone regulating growth in humans. It is synthesized as a 28,000-dalton precursor that is not biologically active. The gene for pre-growth hormone is found on chromosome 17. Growth hormone is part of a family of hormones that include prolactin and human chorionic somatomammotropin (human placental lactogen).

Of the 3, only growth hormone has growth promoting activity. Growth hormone directly acts on cells via a receptor-signaling pathway to cause differentiation and the release of insulin-like growth factors (IGF's). The IGF's promote cell division. Growth hormone synthesis and secretion are regulated by somatostatin and growth hormone-releasing hormone (GHRH). GHRH is produced by the hypothalamus and acts on the anterior pituitary to promote growth hormone release. Somatostatin (growth hormone release-inhibiting hormone) inhibits growth hormone synthesis and secretion. Therefore, excess somatostatin could lead to decreased amounts of growth hormone. A deficiency in growth hormone causes a form of dwarfism.

A 2nd type of dwarfism (Laron dwarf) is caused by defects in the growth hormone receptors. These patients have normal or elevated growth hormone levels but do not secrete IGF's due to the inability of growth hormone to properly signal an increase in IGF secretion. If these patients are administered IGF, growth stimulation is observed indicating the presence of functional IGF receptors.
A 33-year-old woman presents with multiple symptoms; they have been worsening over several months. She notes fatigue, loss of appetite, weight loss, abdominal pains, nausea, as well as an "achiness" throughout her muscles and joints. The patient's family has noticed her skin appears very tanned, despite lack of sun exposure; she also uses more salt on food than ever before. The patient has stable hypothyroidism and takes daily medication. She denies any fever/chills, bowel changes, recent travel, psychosocial changes, or other triggers for her various symptoms.

Her past medical history is remarkable for hypothyroidism. She takes 88 mcg of levothyroxine. She has had 3 pregnancies and a tubal ligation as her only surgery. She has no allergies; she denies the use of tobacco, alcohol, and drugs. She works in retail. Her family history is unremarkable.

Vitals are normal with a BP of 104/64 mm Hg. On physical exam, the patient does have some hyperpigmentation, especially in the nipple/areola region. The remainder of her exam is normal. Weight loss of 8 lbs. is noted from a prior visit.

Fasting, morning labs are drawn with results below.

Urinalysis - Normal
Complete blood count - Normal
Comprehensive metabolic panel- Mildly decreased sodium and elevated potassium, rest normal
Thyroid stimulating hormone (TSH)- Normal (1.8 uIU/mL)
Adrenocorticotropic hormone (ACTH)- Elevated (>200 pg/mL)
C-reactive protein- Normal
Cortisol (morning level)- Decreased (<3 mcg/dL)

Question
What pharmacologic intervention is the most appropriate for this patient's condition?

Answer Choices
1 Decrease the levothyroxine dose
2 Increase the levothyroxine dose
3 Start furosemide
4 Start hydrocortisone
5 Start sodium bicarbonate
Start hydrocortisone
This patient is presenting with Addison disease, a deficiency in the adrenal corticosteroids. The low cortisol and the elevated ACTH confirm this. The symptoms of Addison disease are many and can be confused with other conditions, including some thyroid conditions. They may include: fatigue, weakness, abdominal pain, nausea, anorexia, weight loss, anxiety, irritability, depression, arthralgias and myalgias. Addison disease is a considered an autoimmune condition, and it is often linked with other autoimmune disorders, such as hypothyroidism. Once the condition is identified, the treatment of choice is to start hydrocortisone. The treatment may be IV in acute conditions; oral treatment is appropriate in less urgent cases, and it is usually lifelong.

This patient reports stable hypothyroidism and compliant medication-taking. Furthermore, her TSH result is normal, so it would be inappropriate to decrease the levothyroxine dose or increase the levothyroxine dose. Some common symptoms of hypothyroidism include fatigue, depression, weight gain, constipation, and nail/hair changes. Symptoms of over-replaced thyroid medication can be anxiety, palpitations, and/or weight loss.

In certain instances, when hyperkalemia (elevated potassium) is identified, one treatment may be to start furosemide, due to its effects on renal potassium excretion. However, this patient's hyperkalemia is mild, and once the underlying condition (Addison disease) is treated, the hyperkalemia should resolve without other measures.

This patient has a mild hyponatremia (low sodium); likewise, it should resolve with appropriate replacement of steroids, such as hydrocortisone. It would be inappropriate to start sodium bicarbonate for several reasons. This medication is not intended to raise serum sodium. (Hyponatremia has many potential causes, and fluid status needs to be addressed. Intravenous saline is often part of acute treatments of hyponatremia.) Furthermore, the sodium bicarbonate is primarily used for acidosis, and as an antacid, it is not appropriate for hyponatremia.
Serum Calcium Levels
Explanation
The patient has symptoms of hypocalcemia, a possible complication of thyroid surgery. The parathyroid glands are closely related to the thyroid gland and may be inadvertently removed during surgery. If damaged, the serum calcium levels usually drop within 48 hours of surgery. Symptoms of hypocalcemia include muscle pain, fatigue, and muscle cramps if severe. Chvostek's sign, which is the contraction of ipsilateral facial muscles with a light tap over the facial nerve, and spasm of the carpal muscles (Trosseau's sign) may be seen.

The best screening test for hypocalcemia is the measurement of ionized calcium in the serum. Calcium exists in equilibrium between the fraction bound to albumin and the free or ionized fraction. The biological effects of calcium are dependent on the ionized fraction. Serum calcium level varies with level of serum albumin (calcium binding protein).

Correction for calcium level when albumin is abnormal is as follows:

Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level.

The risk factors for hypocalcemia after thyroid surgery include large goiters, hyperthyroidism, low pre-operative vitamin D levels, and planned extensive neck dissection. Hypocalcemia is prevented to some degree by the administration of large amounts of calcium, usually per oral, and 1,25 dihydroxy vitamin D. In the event of severe hypocalcemia, calcium gluconate may be used via IV. It is important to check magnesium levels and correct levels prior to discharge, as hypomagnesemia can compound hypocalcemia and make it refractory to correction.

Serum TSH, T3, and T4 are incorrect, as thyroid function has no bearing on the patient's symptoms. They are expected to change after thyroid surgery. Typically, TSH levels will rise, and T3 and T4 levels will fall over the ensuing 3 - 6 weeks.

An ABG is incorrect. It may demonstrate low Ca levels, but a direct measure of serum calcium in patients that demonstrates symptoms of hypocalcemia is more accurate and effective.

A CT scan of the neck is incorrect, as it provides no additional information about the person's calcium metabolism.
Explanation
In familial hypercholesterolemia, which is a genetic disorder, the plasma levels of cholesterol and LDL are elevated. In this disease, cholesterol is deposited in many tissues because of the concentrations of cholesterol-LDL in the plasma. The molecular defect results in the absence or deficiency of functional LDL receptors. Therefore, the entry of LDL into the liver and other cells is impaired and all of the deleterious effects of the disease can be attributed to the elevated LDL-cholesterol levels.

High levels of cholesterol have 3 major metabolic effects. Cholesterol inhibits the activity of the enzyme β-Hydroxy-β-methyl-glutaryl-CoA (HMG-CoA) reductase, which catalyzes the rate-limiting step of cholesterol biosynthesis. Cholesterol also inhibits the production of low-density lipoprotein (LDL) receptors by suppressing the transcription of the LDL receptor mRNA. The third point of regulation involves the activation of the enzyme acyl-CoA: cholesterol acyltransferase (ACAT), which esterifies cholesterol for storage.

The LDL receptors are located in specialized regions of the membrane called coated pits. These coated pits contain a protein called clathrin. Clathrin participates in the endocytosis of LDL receptors, as well as other proteins such as transferrin and sialoglycoproteins. Clathrin forms a closed polyhedral lattice around the coated pit forming a coated vesicle. The coated vesicle then loses its clathrin and fuses with an endosome. In the endosome, the ligand is dissociated from the receptor, and sorting of the different components can occur.
Polyuria and polydipsia
Explanation
This patient most likely has diabetes insipidus (DI). The most common presenting symptoms are polyuria and polydipsia. Diabetes insipidus is primarily a disorder in which the arginine-vasopressin (AVP) secreting cells are destroyed, causing a deficiency in antidiuretic hormone (ADH). The condition can be controlled with desmopressin, but in patients with very mild symptoms, no treatment may be preferred.

Agnosia is the inability to recognize objects. It can be associated with dementia, head trauma, and brain tumors. The vasopressin challenge test, which should reduce thirst and urine output in patients with diabetes insipidus, would not be an appropriate test; desmopressin would not be suggested as a treatment. An MRI may be part of the workup for agnosia, and there could be variable findings.

Diplopia and blurred vision should trigger a thorough neurologic exam and eye exam, with a possible MRI for further workup. As is the case with agnosia, the vasopressin challenge test and use of desmopressin have no role in regard to the patient's visual symptoms.

Headaches are common, and most do not require specialized testing or imaging. If they present with 'red flags' that might indicate a more serious disorder (additional neurologic symptoms, new onset later in life, etc.), MRI of the brain is reasonable. Vasopressin challenge would not be used. Diabetes insipidus very rarely presents with headaches.

Memory loss is not associated with these tests, findings, or treatments. A complaint of memory loss in a 46-year-old should be evaluated with a thorough neurologic exam; psychological testing and brain imaging should be considered as possibilities.
Encourage a low-calorie diet, modest protein and carbohydrate restriction with exercise
1 popular diet therapy is the high-protein diet; patients consume >25% of calories from protein sources. Government guidelines typically suggest protein intake to be in the <20% range. Although these diets may assist in weight loss in the short term (≤6 months) by increasing satiety and decreasing postprandial sugar fluxes and insulin surges, their long-term benefit is less clear.

Diets suggested for diabetics typically include a combination of food groups including carbohydrates, proteins, and fats. Weight loss typically assists with glycemic control and reduces insulin resistance. Some diabetic patients (1 diagnostic criterion is a random sugar >200 mg/dL) can control their diabetes with diet alone.

This patient has obesity, hyperglycemia, and proteinuria, a marker of kidney disease, and she should follow modest reductions in protein intake. The kidney disease outcome initiative (National Kidney Foundation) suggests modest reductions in protein intake. Severe protein restriction is not suggested for diabetics or patients with kidney disease because it may not prevent declines in kidney function; it may contribute to protein, vitamin, and nutrient malnutrition.

Although short-term protein loads will increase glomerular filtration rate, long-term, high-protein diets may cause a decline in glomerular filtration rate and kidney function, particularly in patients with diabetes and existing kidney disease. Dietary sources of protein (e.g., chicken, lamb, and beef) may include advanced glycosylation end products (AGE); these are the amino portions of proteins that have reacted through glycation and oxidation to cause the formation of sugar proteins. Consumed AGEs and AGEs created when excess proteins link with excess sugar may lead to cross-linking and scarring of the matrix and glomerular wall portions of the kidney, leading to scarring. Proteins may also promote tissue damage by generating free radicals and causing oxidative stresses. Vegetable-based proteins appear to have lesser effects on renal function than do animal-based proteins.
Explanation
Desmopressin acetate (DDAVP) is the correct answer, as this medication is used as the first-line treatment in patients with central or primary diabetes insipidus (DI). Arginine vasopressin (AVP), or antidiuretic hormone, is produced by the pituitary gland and works on the renal tubules within the kidney to concentrate the urine and reduce water loss. DI occurs when there is a deficiency in AVP, and these patients produce large amounts of dilute urine. As a result, patients can experience excessive thirst, polyuria, nocturia, headache, dehydration, and disturbances in vision. Central or primary DI can be diagnosed with 24-hour urine collection or vasopressin challenge test. Once the diagnosis is established, the first line treatment is usually desmopressin acetate, which is a synthetic form of AVP. It has a longer antidiuretic action than AVP and does not constrict smooth muscle. DDAVP is available in oral, nasal, and injectable preparations. While being treated, it is important to control fluid balance in order to prevent dehydration, monitor the patient's weight daily, and monitor electrolytes.

Hydrochlorothiazide is not the correct answer, as this medication can be used in cases of nephrogenic DI rather than central DI and as a treatment for hypertension. Nephrogenic DI occurs in the presence of normal AVP production by the pituitary gland with insensitivity to AVP in the kidney. There is a disorder in the renal tubular function that results in the inability to respond to the presence of AVP. In these cases, hydrochlorothiazide can be given in a 25 mg dose either once or twice daily.

Indomethacin is not the correct answer. Indomethacin is a non-steroidal anti-inflammatory that is typically used in the treatment of osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. However, it can also be used in the treatment of nephrogenic DI because indomethacin inhibits prostaglandins, which reduces urine output by decreasing the renal blood flow. This would not be effective in the treatment of central DI.

Amiloride is not the correct answer. Amiloride is often added to HCTZ in order to increase the diuretic effects. However, this is a treatment course that is used in nephrogenic DI and not central DI.

Glucophage is not the correct answer, as this medication is a biguanide used in the treatment of diabetes mellitus, not diabetes insipidus.
A reduction in the amount of LDL receptors on hepatocytes
LDL (low density lipoprotein) is removed from the circulation by either LDL receptors on hepatocytes or by scavenger cells such as monocytes or macrophages. When there is a decrease in LDL receptors on hepatocytes, or when LDL levels exceed receptor availability, the amount of LDL that is removed by scavenger cells is greatly increased. The LDL receptors are deficient or defective in the genetic disorder known as familial hypercholesterolemia (type 2A). Patients with this primary hypercholesterolemia disorder may be heterozygotes or homozygotes, with homozygotes developing cutaneous xanthomas and myocardial infarctions in childhood.

HDL (high density lipoprotein) is synthesized in the liver and transports cholesterol from the peripheral tissues back to the liver; an inverse relationship exists between HDL levels and the development of atherosclerosis.

Chylomicrons are involved in the transport of dietary (exogenous pathway) triglycerides and cholesterol that have been absorbed from the gastrointestinal tract, which are then transported to the skeletal muscle and adipose. This patient denies a high triglyceride diet.

The production of VLDL (very low density lipoprotein) is increased by the liver as a result of a high calorie diet, obesity, and diabetes mellitus. VLDL represents the primary pathway for transport of endogenous triglycerides produced in the liver; these are then carried to muscle and fat cells. Elevated VLDL levels are not consistent with familial hypercholesterolemia (type 2A).

Diabetes mellitus is a cause of secondary hypercholesterolemia, not primary hypercholesterolemia.
Metyrapone
Explanation
This patient is demonstrating signs and symptoms consistent with Cushing's syndrome. Medications used in the management of Cushing syndrome include somatostatin analogs (pasireotide), adrenal steroid inhibitors such as metyrapone, ketoconazole, and etomidate, glucocorticoid receptor antagonists (mifepristone), and adrenolytic agents (mitotane).

Metyrapone blocks 11-beta-hydroxylase activity, the final step in cortisol synthesis. Therapy is begun at 1 g/d divided into 4 doses and increased to a maximum dose of 4.5 g/d. Adverse effects present from increases in androgen and mineralocorticoid precursors and include hypertension, acne, and hirsutism.

Ketoconazole has been the most popular and effective of these agents for long-term use and usually has been the agent of choice. However, the FDA has issued a black box warning that states clinicians should no longer prescribe ketoconazole, except to treat some life-threatening fungal infections; this is due to increased risk for severe hepatotoxicity, including fatalities and liver transplantation, adrenal insufficiency, and adverse drug interactions.

Prednisone is not indicated in the treatment of Cushing syndrome. Cushing syndrome is caused by prolonged exposure to elevated levels of either endogenous glucocorticoids or exogenous glucocorticoids. Exogenous use of glucocorticoids should always be considered and excluded in the etiology of Cushing syndrome.

Tacrolimus is a topical immunosuppressant agent useful in the treatment of psoriasis, while mupirocin is a topical antibiotic useful in the treatment of topical skin infections such as impetigo.
Prednisone
Explanation
This patient likely is suffering from Cushing's syndrome, which is also known as hypercortisolism. Consequences of excessive levels of circulating cortisol, no matter the etiology, will lead to certain signs and symptoms, such as central obesity, thin extremities, a moon face, a buffalo hump, supraclavicular fat pads, protuberant abdomen, and oligomenorrhea/amenorrhea; in men, erectile dysfunction is a possibility. The most common etiology of Cushing's syndrome is a benign pituitary adenoma secreting excessive ACTH. Primary clinical intervention is transsphenoidal selective resection of the pituitary adenoma. Once this has been completed, patients typically suffer from a suppression of pituitary corticotrophs; therefore, treatment with hydrocortisone or prednisone replacement therapy is necessary for a range of 6 - 36 months post-surgery.

Diabetes Type II is caused by insulin resistance in tissues to circulating endogenous insulin. Eventually insulin is unable to be produced by the pancreatic islet cells and an exogenous supply is required to prevent significant hyperglycemia and its related co-morbidities. Features of these patients include central obesity (specifically visceral obesity), with less fat noted on extremities. Insulin, although usually not the common initial medication considered at for patients with diabetes, is one of the many types of pharmaceutical treatments available for these patients.

Hypothyroidism and hyperthyroidism both are related to dysfunction of the thyroid gland; hypothyroidism is due to failure of the thyroid gland itself or deficient supply of pituitary TSH (thyroid stimulating hormone). Symptoms exhibited with hypothyroidism are weight gain, fatigue, lethargy, depression, weakness, menses irregularities, athralgias, muscle cramps, cold intolerance, dry skin, and constipation; signs present may include thinning hair, brittle nails, bradycardia, or even peripheral edema. Typical treatment for hypothyroidism is a dose of daily levothyroxine.

Hyperthyroidism is the disease state in which there is an excessive serum level of T3 and or T4 along with suppressed TSH levels. Signs and symptoms may include (depending on the severity) restlessness, nervousness, heat intolerance, increased sweating, weight loss, palpitations, atrial fibrillation, exophthalmos, or even pretibial myxedema. The medication that is commonly utilized in treatment of hyperthyroidism is primarily propylthiouracil, which is also frequently referred to as PTU.

Diabetes insipidus (DI) is antidiuretic hormone deficiency. A sign/symptom of DI is an extreme, unquenchable thirst with a very specific craving for ice water. Patients also will have significant polyuria or hypernatremia. Pharmaceutical treatment for DI is typically desmopressin.
Explanation
Asking her to come to clinic and have her total and differential blood count done is the correct answer. One uncommon, but well recognized, side effect of antithyroid medications is the potential to cause rapid agranulocytosis, characterized by a very low circulating neutrophil count. Patients usually develop agranulocytosis during the first 3 months of therapy. The drug most commonly associated with it is propylthiouracil. Symptoms most commonly encountered include a fever, sore throat, myalgia, and rigors. Any patient with these symptoms, especially within the first few weeks of initiating therapy, must have their white count checked. The incidence of such side effects is well below half a percent, thus making it economically unviable to routinely monitor counts. The suggested method of treatment once agranulocytosis is proven is the administration of broad spectrum antibiotics with intravenous granulocyte colony stimulating factor. This results in rapid resolution of neutropenia.

Increasing her dose of carbimazole is incorrect. That would only worsen the problem.

Self administration of thyroxine is incorrect. The patient has hyperthyroidism to begin with and is not exhibiting any signs of hypothyroidism.

Prescribing antibiotics is incorrect. While it may be done, the neutrophil count must first be determined in order to rule out neutropenia. If the white count is normal, a mild pharyngitis may not need antibiotics in any case.

Prescribing salt water gargles and acetaminophen is incorrect. The neutrophil count must first be determined.
Surgical exploration of the neck
Explanation
Over 90% of cases of hypercalcemia in the elderly are caused by primary hyperparathyroidism or malignancy. The rest are caused by medications (e.g. thiazide diuretics), vitamin D intoxication, sarcoidosis, renal failure, hyperthyroidism, and milk-alkali syndrome. Most patients with primary hyperparathyroidism are asymptomatic and are identified incidentally. These patients should be monitored every 6 to 12 months. Most patients with primary hyperparathyroidism do not have disease progression; therefore, immediate therapy is unnecessary.

Symptoms of primary hyperparathyroidism manifest in the form of fatigue, weakness, alterations in mental status, hypertension, kidney stones, and gastrointestinal symptoms such as anorexia, nausea, and constipation. Osteoporosis is also common finding. This patient now has symptoms of anxiety and confusion that warrant intervention. Surgery in the form of bilateral neck exploration, and parathyroidectomy is the preferred method of treatment in patients with symptomatic hyperparathyroidism.

Medical management is an alternative to surgery in asymptomatic patients, patients who refuse surgery, and those who are considered poor surgical candidates. Adequate hydration should be undertaken, and medications that increase serum calcium levels (e.g., thiazide diuretics, lithium) should be avoided or discontinued. Maintaining adequate vitamin D intake is also important; vitamin D deficiency stimulates parathyroid hormone secretion and further bone resorption.

Oral bisphosphonates, such as alendronate, can be used in patients with primary hyperparathyroidism in order to help preserve bone density; however, this is not the preferred treatment method. Subcutaneous calcitonin is also effective in this regard, but it does not treat the primary cause of the disorder. Oral phosphate supplementation and a low calcium diet can help lower serum calcium levels, but surgery remains the most definitive treatment. In postmenopausal women, estrogen replacement therapy suppresses bone turnover, decreases urinary calcium excretion, and increases bone mineral density. However, estrogen therapy also increases the risk of stroke, coronary artery disease, and breast cancer. Therefore, it is not first-line therapy for primary hyperparathyroidism in patients who are good surgical candidates.
Diffuse non-toxic goiter
Explanation
The clinical presentation, exam, and lab findings are suggestive of diffuse non-toxic goiter.

Diffuse non-toxic goiter, colloid goiter, or simple goiter is the name given to the diffuse enlargement of the thyroid gland unaccompanied by hyperthyroidism. Most cases are in the euthyroid stage, although they have passed a transient phase of hypothyroidism due to iodine deficiency. TSH levels are normal or slightly increased. Goiter occurs in 2 forms, either endemic or sporadic. The endemic form occurs due to the lack of dietary iodine or due to the intake of goitrogens like consumption of cassava root, cabbage, cauliflower, turnips, etc. Endemic goiter is most prevalent in high mountainous areas. Sporadic form is more common in the U.S. and in Europe, and the etiology is not known. This is said to be multifactorial in origin. Generally, most simple goiters are asymptomatic, manifesting as a painless symmetric enlargement of the thyroid gland. Spontaneous hemorrhage may cause sudden onset of pain and swelling. Examination of the gland reveals a nontender, soft gland with symmetric enlargement, without any palpable nodules. A low urinary iodine level (<10 μg/dL) is supportive of a diagnosis of iodine deficiency goiter. A thyroid function test generally shows a low total T4, with normal T3 and TSH. Treatment is with iodine or thyroid hormone replacement, which induces variable levels of goiter regression, depending on the duration of swelling and the degree of fibrosis.

Multinodular goiter is an end stage of a long-standing simple goiter, and it is characterized by an extreme degree of thyroid enlargement with characteristic nodularity. Most cases are euthyroid, but about 10% cases develop thyrotoxicosis. Large goiters can cause compressive symptoms such as dysphagia, respiratory distress (due to tracheal compression), or plethora (venous congestion). On examination of the thyroid gland, the architecture is distorted with presence of multiple nodules of varying size. A thyroid function test is usually normal.

Toxic nodular goiter is characterized by subclinical hyperthyroidism or mild thyrotoxicosis in addition to features of goiter. The clinical presentation of toxic nodular goiter includes tachycardia, nervousness, atrial fibrillation or palpitations, tremor, or weight loss. Plummer disease or toxic nodular goiter differs from Graves' disease by lack of ophthalmopathy and dermatopathy. The thyroid function test shows low TSH level with normal or minimally increased T4 and elevated T3, which is usually of a greater degree than T4. Heterogeneous uptake and multiple regions of elevated and diminished uptake is evident on thyroid scan.

Graves' disease is characterized by hyperthyroidism, diffuse thyroid enlargement, and ophthalmopathy. It is an autoimmune disease. Thyroid function test shows low TSH level and elevated total and unbound thyroid hormone levels.

De Quervain thyroiditis is characterized by a transient inflammation of the thyroid gland, which may be due to viral infections. Patients generally present with a painful, enlarged thyroid gland, and it is sometimes associated with fever. Thyroid function test evolves through 3 distinct phases: the thyrotoxic phase, the hypothyroid phase, and the recovery phase. The thyrotoxic phase shows elevated T4 and T3 levels and suppressed TSH levels. A high ESR and low radioiodine uptake helps in confirming the diagnosis.
Explanation
Testing the urine with a dipstick for microalbumin is the most appropriate screening test for diabetic nephropathy. Results of 2 or 3 tests for microalbuminuria should be more than 30 mg per day or 6-month period to diagnose a patient with diabetic nephropathy. An early morning sample is preferred, although not strictly required. The dipstick measures a spot albumin to creatinine ration in the urine, which is a reliable indicator of albuminuria.

Screening for diabetes is recommended at the time of diagnosis with Type II diabetes and 5 years after diagnosis of Type I diabetes. Some authorities recommend earlier screening in individuals with Type I diabetes with poor metabolic control. Without any intervention, over 80% of patients with microalbuminura will develop overt nephropathy within 10 - 15 years. Of this population, roughly 20% will go on to develop renal failure.

Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the U.S. and Europe. This is attributed to the following: 1) the increasing prevalence of diabetes; 2) increased acceptance of diabetic patients to dialysis programs that were earlier excluded; and 3) increase longevity of diabetic patients.

As per the findings of the Diabetes Control and Complications Trial Research Group, tight blood sugar and blood pressure control are the most important variables to control in order to prevent nephropathy. An HbA1c of <7% and BP of <135/80 mmHg are the standard of care. ACE inhibitors are the drug of choice for hypertension, with non-dihydropiridine calcium channel blockers as the alternative if ACE is contraindicated. At an early stage, the use of ACE inhibitors has been shown unequivocally to delay the progression of nephropathy.

Creatinine, blood urea, and urine specific gravity are incorrect. While they are indicators of renal function, none of them are as sensitive or cost effective as measuring a spot urine albumin to creatinine ratio; however, they are measured in order to monitor renal function and assess the side effects of medications, particularly ACE inhibitors and oral hypoglycemic drugs.

A 24-hour urine protein is incorrect. It is an excellent test with high sensitivity. However, it requires urine to be collected over 24 hours, which is cumbersome; therefore, it is inappropriate as an initial screening test. It is sometimes used in patients who are dipstick positive in order to quantify the excreted protein.
A 48-year-old man presents to the family practice clinic for evaluation of fatigue, weakness, and nausea. He reports that his symptoms have progressively worsened over the last 6 - 8 months. He reports fatigue despite adequate sleep; he is also experiencing an overall feeling of muscle weakness, nausea with occasional vomiting, a weight loss of about 12 pounds, headaches, and muscle aches. His wife thinks he appears tanned year-round, despite a lack of sun exposure. He admits feeling anxious and somewhat irritable, but he denies any major psychosocial or traumatic events surrounding onset of symptoms. Prior to the onset of his symptoms, he was healthy and active.

His past medical history reveals no chronic medical conditions, no medication use, and no history of surgery; he does not have any allergies. His family history is significant for thyroid disease in a sister and his mother; there is also a history of diabetes mellitus type I in a brother. He teaches high school, and he lives with his wife and children; he denies the use of tobacco, alcohol, and drugs.

On physical exam, he is noted to be hypotensive and hyperpigmented. The remainder of his physical exam is normal.

Several labs are performed, and the results are as follows:
Urinalysis- Normal
Complete blood count- Mildly decreased hemoglobin and hematocrit
Comprehensive metabolic panel- Mildly decreased sodium and elevated potassium, rest normal
Adrenocorticotropic hormone (ACTH)- Elevated
Cortisol (morning level)- Decreased
ACTH stimulation test- Decreased cortisol

Question
Once this patient is diagnosed, what choice represents the most important intervention for his presumed condition?

Answer Choices
1 Increase dietary sodium
2 Initiation of antidepressant with anti-anxiety properties
3 Initiation of steroids
4 Refer to oncologist
5 Restrict dietary potassium intake
Initiate Steroids
Explanation
This patient is presenting with a corticoadrenal insufficiency, which is also known as Addison's disease. In the United States, this rare disease is most often linked with autoimmune causes. The affected patient will have a variety of symptoms related to low glucocorticoid and mineralocorticoid production. Signs and symptoms include fatigue, nausea, vomiting, headaches, anorexia, myalgias, arthralgias, muscle weakness, anxiety, mental irritability, hyperpigmentation, hypotension, hyponatremia, hyperkalemia, anemia, and many more. The mainstay of treatment is initiation of steroids, often with oral hydrocortisone, unless urgent IV treatment is needed.

Patients with Addison's disease commonly have hyponatremia and hyperkalemia. They can be instructed to increase dietary sodium, especially in times of exercise and hot weather. However, this alone will not address the underlying adrenal insufficiency, and failure to initiate steroid treatment will risk patient deterioration.

With a variety of somatic and psychiatry complaints, a patient presenting like this may be falsely given a psychiatric diagnosis, and he may be treated with initiation of an antidepressant with anti-anxiety properties; however, the anxiety and irritability are symptoms of the adrenal disorder, and they should improve with treatment of the underlying disorder. It would be reasonable to monitor this patient and possibly treat him with antidepressants if his symptoms do not resolve.

While Addison's disease is serious and chronic, it is not malignant. This patient's presentation with weight loss, nausea, and fatigue could be suggestive of cancer. However, with the laboratory values indicating adrenal insufficiency, it would be inappropriate to refer the patient to an oncologist.

Even as a mild hyperkalemia is indicated on this patient's lab values, restriction of dietary potassium is not an appropriate treatment of his primary condition. The hyperkalemia is a result of the adrenal insufficiency. With appropriate treatment with steroids, such as hydrocortisone, the electrolyte abnormalities are likely to improve without additional intervention.
Explanation
The correct response is intravenous hydrocortisone 150 mg/daily on day of procedure, with a taper over next 2 - 3 days to usual daily replacement dose if the postoperative period is otherwise uncomplicated.

Cortisol has many critical metabolic and endocrine functions that are necessary for human survival, particularly during times of stress. Everyday health and illness, surgery, anesthesia, trauma, and severe illnesses result in elevated plasma ACTH and cortisol levels. Those that are adrenally insufficient (such as patients diagnosed with Addison's disease) have very little or no function of this type of endocrine function, thereby predisposing them to inappropriate body reactions to stress that can result in devastating morbidities. External corticosteroids are prescribed to these patients to take on a daily basis.

For this reason, patients with any type of adrenal insufficiency must have an appropriate treatment plan in regards to their corticosteroid therapy in order for them to produce an appropriate immune response to the stress of surgery. There is no universally accepted regimen for corticosteroid supplementation during the surgical and postoperative time period. A recommended dosing plan should be based on the severity of the surgery stress as well as the medical stress that the patient will most likely endure intra- and post-operatively. Cardiothoracic surgery and its postoperative time period are categorized as severe in terms of the effects on the body. For this reason, the most appropriate plan would be Intravenous hydrocortisone 150 mg/daily on day of procedure, with a taper over next 2 - 3 days to usual daily replacement dose if the postoperative period is otherwise uncomplicated.
Physical examination especially genitalia
Explanation
The correct response is a physical examination (especially genitalia).

Gynecomastia may be either physiologic or pathologic. Physiologic gynecomastia has normal peaks in the neonatal period and in adolescence due to a relative increase in estrogen. Age-related gynecomastia (usually between 50 and 70 years of age) results from an increase in fatty tissue and decrease in hormone levels. Pseudogynecomastia (usually seen in obese men) is enlarged breasts without a palpable mass.

The most reassuring aspect of this patient's gynecomastia is his age. If his symptoms were occurring outside the neonatal or adolescent period, or if they were associated with physical or laboratory abnormalities, a more aggressive workup would be warranted. The examiner should pay particular attention to the signs of puberty, particularly testicular size, in order to rule out conditions such as Klinefelter's syndrome (which may present with gynecomastia). Therefore, the most important next step in this patient's workup is a thorough physical examination; this will ensure normal puberty and rule out a testicular mass as a cause of a hormone imbalance and gynecomastia. Physiologic gynecomastia generally resolves within 2 years without any treatment.

Both prescription and illicit drugs can cause gynecomastia. Common offenders include some antidepressants, antibiotics, medication used to treat HIV or heart disease, marijuana, anabolic steroids, heroin, and chronic alcohol abuse. Asking about medications and drug use would certainly be an important part of the medical history in the workup of gynecomastia.

Liver disease (cirrhosis) is a very common cause of gynecomastia. Liver disease causes impaired metabolism of androstenedione, a precursor of estrogen and testosterone. In addition, patients with liver disease may be treated with spironolactone, a medication that is known to cause gynecomastia. This patient has no history or signs of liver disease.

A mammogram would not be indicated in this patient because the breast changes are bilateral and there is a lack of concerning features (e.g., a firm, discrete mass, bloody nipple discharge, and/or skin changes). Breast cancer is rare in men, and this patient likely does not have pathologic gynecomastia.

Thyroid disease (both hypo and hyper) can cause gynecomastia. In hyperthyroidism, this is a result of an increased conversion of androgen to estradiol. Hypothyroidism results in a lower level of testosterone with a resulting increase in estradiol production. This particular patient has no signs of symptoms of thyroid disease.
Diabetes Insipidus
Explanation
This patient is suffering from diabetes insipidus (DI). Characteristics of this disease process include an increase in thirst and the passage of large quantities of urine. The underlying pathologic feature of DI is a deficiency of vasopressin or a resistance to available vasopressin. There are a multitude of disease states that lead to DI, and the patient is most likely suffering from an acquired form of vasopressin-resistant diabetes insipidus. Disease states that lead to this form of DI can include pyelonephritis, renal amyloidosis, potassium depletion, Sj?gren's syndrome, and the use of certain medications; in the patient's case, the use of lithium resulted in her DI. Chronic use of lithium can lead to lithium toxicity, and it manifests as described in the patient scenario. This is a common cause of DI in adult patients.

Hypothyroidism is much lower on the differential due to the signs and symptoms being inconsistent. Findings such as weakness, fatigue, cold intolerance, constipation, weight changes, depression, and/or menstrual abnormalities would be some of the multiple features evident in patients with hypothyroidism.

Hypoparathyroidism is also not as likely. Signs and symptoms of the acute phase of this disease include tetany, muscle cramps, irritability, altered mental status, and convulsions; a tingling sensation around the circumoral area, hands, and feet is almost always present.

Cushing's disease is due to manifestations of hypercortisolism secondary to adrenocorticotropic hormone (ACTH) hypersecretion by the pituitary gland. Some features include (but are not limited to): central obesity, apparent moon face or buffalo hump, purple striae, muscle wasting, hirsutism, psychological changes, hypertension, weakness, headache, backache, and poor wound healing. None of the signs or symptoms listed matches the patient's history.

Diabetes mellitus (DM) may also be considered in this patient scenario given the symptoms of polydipsia and polyuria described as well as her family history. The main cause of this type of diabetes is that patients develop increased tissue insulin insensitivity, which is also termed insulin resistance. Some key components of the patient's history are not evident in diabetes mellitus. Nocturnal enuresis is not usually a significant symptom in patients with DM, although patients with DM may have complaints of polyuria, polydipsia, weakness, fatigue, blurred vision, vulvovaginitis, and peripheral neuropathy; they may even be asymptomatic.
Parathyroid Adenoma
Explanation
Parathyroid adenoma is the correct response.

The patient has hypercalcemia that is contributing to her recurrent nephrolithiasis. Patients with hypercalcemia may be asymptomatic or present with "bones, stones, abdominal groans, psychic moans, with fatigue overtones." The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy, accounting for over 90% of cases of hypercalcemia. To determine the cause of hypercalcemia, serum ionized calcium, phosphate, intact parathyroid hormone (iPTH), and urine calcium levels should be evaluated. If malignancy is suspected, appropriate workup should be performed. This patient has elevated ionized calcium, elevated calcium in her urine, and hypophosphatemia, with elevated parathyroid hormone levels consistent with primary hyperparathyroidism.

Primary hyperparathyroidism is caused by unregulated PTH secretion. In 80% of cases, it is caused by a single parathyroid adenoma. It is more common in patients over the age of 50 and affects women more than men. Laboratory results show increased serum and urine calcium, increased iPTH, and decreased or normal serum phosphorous. Imaging is not necessary, but it may be used in a preoperative mapping of the parathyroid glands. Medical treatment includes fluids, bisphosphonates, or cinacalcet. Symptomatic patients can be cured with a parathyroidectomy. Calcium and vitamin D supplementation may be required for a reactive secondary hyperparathyroidism occurring after surgery.

Patients with chronic kidney disease will have increased blood urea nitrogen and creatinine levels. They develop a secondary hyperparathyroidism due to decreased vitamin D metabolism, resulting in decreased serum calcium levels and increased PTH levels with increased serum phosphorus levels.

Patients with hypercalcemia can develop polyuria and polydipsia due to nephrotic diabetes insipidus. These symptoms can be similar to diabetes mellitus (DM). In DM, the serum calcium, phosphorus, and parathyroid levels will be normal with elevated blood glucose levels.

Thiazide diuretic use can result in hypercalcemia, but the urine calcium level will be low. PTH and phosphorus levels will be normal.

Malignancy should be evaluated as a possible cause of hypercalcemia. If the patient has not undergone routine screenings, they should be done. The PTH level will be low in a patient with malignancy-related hypercalcemia.
Neurohypophysis
Explanation
This patient has signs and symptoms of diabetes insipidus. Central diabetes insipidus occurs when there is deficient antidiuretic hormone (ADH) secretion from the posterior pituitary (neurohypophysis). In central diabetes insipidus there will be a low ADH level. Nephrogenic diabetes insipidus occurs when the kidney fails to respond to ADH. The collecting duct is the portion of the kidney that is actually responsive to ADH In nephrogenic diabetes insipidus; ADH levels will be normal to elevated. In a patient with central diabetes insipidus, administration of aqueous vasopressin will result in an increase in urine osmolarity above plasma osmolarity. This will not be the cause in a patient with diabetes of nephrogenic origin. Central diabetes insipidus can be caused by granulomatous disease (e.g., sarcoidosis), head trauma, intracranial neoplasm, and some other conditions.

The anterior lobe of the pituitary is the adenohypophysis. The anterior lobe of the pituitary secretes follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, growth hormone (GH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) (and the corticotropin-related peptides).

The glomerulus is a specialized capillary tuft. The endothelium of the glomerulus is fenestrated; the glomerulus is surrounded by Bowman's capsule. A renal corpuscle consists of the glomerulus and Bowman's capsule. A renal corpuscle is sometimes called a Malpighian corpuscle. Renal corpuscles are seen in the kidney cortex.

The loop of Henle is part of the nephron. It is shaped like a hairpin; the proximal convoluted tubule leads into the descending limb of the loop of Henle. The ascending limb of the loop of Henle goes to the distal convoluted tubule.
RET mutation test in the patient
Multiple endocrine neoplasia type 2A (MEN 2A) is a rare familial autosomal dominant multiglandular syndrome. MEN 2A is diagnosed clinically by the occurrence of 2 or more specific endocrine tumors in a single individual or in close relatives: medullary thyroid carcinoma; hyperparathyroidism (hyperplasia or multiple adenomas), pheochromocytomas (often bilateral); or Hirschsprung disease. Patients with MEN 2A should have genetic testing for the RET proto-oncogene (RET) mutation. RET mutation test identifies about 95% of affected individuals. If the mutation is present, the first-degree relatives may be tested for the specific RET mutation; each kindred has a specific RET codon mutation that determines MEN 2 A variation (e.g., the age of onset or the aggressiveness of medullary thyroid cancer). Both the specific mutation and family history should guide you in the further management. Because of the incomplete penetrance, about 30% of those with such mutations never manifest endocrine tumors. In the affected family members, you may consider regular check-ups for MEN 2-associated pheochromocytomas (24 hours urine for elevated catecholamines and catecholamine metabolites, especially vanillyl-mandelic acid at the earliest age possible), medullary thyroid carcinoma (serum calcitonin or serum calcitonin/pentagastrin-stimulated calcitonin levels), thyroid tumours (ultrasound and fine-needle aspiration), and annual testing for parathyroid abnormalities (simultaneously elevated serum calcium and parathyroid hormone levels with an elevated urinary calcium to creatinine ratio). The results should guide you in the scheduling profilactic thyroidectomy.

An RET mutation test should be performed in children if the mother has RET mutation. Such testing is highly accurate and sensitive for presymptomatic identification of at-risk individuals and test for the specific mutation will determine the best next step in order to reduce morbidity and mortality.

Plasma calcitonin levels in children to test for the presence of medullary thyroid carcinoma should be considered if they are positive for the specific RET mutation in order to decide the further steps of management. This test is also used to look for the possible recurrence of MTC after treatment.

Prophylactic thyroidectomy shall be planned only in the presence of the specific mutation and case histories of family members. Children harboring this mutation are advised to have a prophylactic total thyroidectomy by the age 6 years.

While carcinoembryonic antigen (CEA) is often elevated in thyroid cancers, it is not specific; higher than normal levels may also be due to the breast, colon, lung and pancreatic cancers; other causes include liver and gallbladder disorders, heavy smoking, inflammatory bowel disease, lung infections, pancreatitis, peptic ulcer disease etc. However, CEA can be useful after the thyroidectomy if one suspects a reccurrence of the tumor.
Insulinoma
Her low blood glucose levels indicate an insulinoma.

The endocrine portion of the pancreas is housed in the islets of Langerhans. Tumors that arise from this area are referred to as islet cell tumors. The specific type of tumor depends on the cell type involved. Typically, the tumor is named based on the hormone it is secreting.

An insulinoma is an islet cell tumor. Insulin is produced by the beta cells of the islets of Langerhans. Therefore, an insulinoma is a tumor of the beta cells. An insulinoma is the most frequently occurring islet cell tumor. Hypoglycemia, secondary to the insulin secretion, is a symptom.

Verner-Morrison syndrome is due to a VIPoma. This is an endocrine tumor of the pancreatic islets of Langerhans. It secretes vasoactive intestinal polypeptide. Vasoactive intestinal polypeptide is produced by the D1 cells of the islets of Langerhans. Therefore, a VIPoma is a tumor of the D1 cells. Other names for a VIPoma include pancreatic cholera and WDHA-syndrome (watery diarrhea, hypokalemia and achlorhydria).

Gastrinomas are most often due to islet cell tumors. On occasion, gastrinomas can arise outside of the pancreas. Peptic ulcers, secondary to the excessive gastrin secretion, are frequent. Gastrinomas and peptic ulcerations are referred to as the Zollinger-Ellison syndrome.

A glucagonoma is an islet cell tumor. Glucagon is produced by the alpha cells of the islets of Langerhans. Therefore, a glucagonoma is a tumor of the alpha cells. Diabetes can be seen with a glucagonoma. Other symptoms include a skin rash, weight loss, and anemia. A glucagonoma is a rare islet cell tumor.

A somatostatinoma is an islet cell tumor. Somatostatin is produced by the delta cells of the islets of Langerhans. Therefore, a somatostatinoma is a tumor of the delta cells. Somatostatinoma is a rare islet cell tumor.
low potassium
Trunk obesity, moon face, purple stretch marks on the abdomen, and buffalo hump are typical symptoms of Cushing's syndrome due to chronic exposure to corticosteroids. Other symptoms are muscle wasting and weakness, thin and atrophic skin, poor wound healing, easy bruising, hypertension, osteoporosis, renal stones, glucose intolerance, psychiatric problems, and virilism in females. Due to increased secretion or administration of ACTH, too much aldosterone is produced. The latter results in increased secretion of K+ and H+ ions through the kidney, and ends in hypokalemia (low potassium) and metabolic alkalosis. Cardiac symptoms are usually minimal until serum potassium levels are <3 mEq/l. ECG changes include ST-depression; decreased and sometimes negative T; U-wave, and extrasystole (remember: "no pot [assium], no t [ea], but 'U' "). In severe hypokalemia, you can find premature ventricular and atrial contractions, as well as arrhythmia, which can lead to cardiac arrest.

Hyperkalemia presents in the ECG as shortening of the QT-interval and tall, peaked T-waves and then proceeds to nodal and ventricular arrhythmia, widening of the QRS complex, PR prolongation, disappearance of P-wave, and finally degeneration of the QRS complex to sine wave and asystole. Clinical symptoms are arrhythmia, paresthesias, hyporeflexia, muscle weakness, obstipation, and acidosis.

Hypernatremia is usually generated when water losses exceed sodium losses in combination with inadequate water intake. The symptoms are CNS dysfunction-like confusions, seizures, coma, hemorrhages, and thrombosis.

Hyponatremia is usually caused by renal retention of water, while sodium is excreted. Typical symptoms are confusion, lethargy, and altered mental status. Cerebral edema, brain herniation, coma, and death can occur.

Hypomagnesemia is often caused by inadequate intake. The symptoms include tetanus, tremor, seizures, nausea, vomiting, lethargy, weakness and mental alteration.
Hashimotos
The presence of antithyroid antibodies and the typical histology points to a diagnosis of Hashimoto's thyroiditis (chronic lymphocytic thyroiditis). It is the most common form of thyroiditis, and most common cause of hypothyroidism in the US. This condition is characterized by thyroid cell destruction by various antibody-mediated immune processes. The gland appears diffusely enlarged and firm. Increased circulating levels of antithyroid peroxidase or anti-thyroglobulin antibodies is a diagnostic feature.

Hashimoto's thyroiditis is a histological diagnosis characterized by infiltration of lymphocyte and plasma cells, reduced size of the thyroid follicles containing sparse colloid, and fibrosis along with presence of follicle with oxyphilic change called Hurthle cells.

The image shows replacement of thyroid follicles by lymphoplasmacytic infiltrate with germinal centers (indicated by arrows).

Riedel's thyroiditis is characterized by dense fibrosis, which results in a stony hard enlargement of the thyroid gland. It is the rarest form of thyroiditis. Histological features of Riedel's thyroiditis include a fibro-inflammatory process involving a portion or the entire thyroid gland and the presence of fibrotic extension into the adjacent structures beyond the thyroid capsule.

Subacute painless thyroiditis is a self-limiting disease process having triphasic clinical presentation of hyperthyroidism, hypothyroidism, and return to euthyroid state. Thyroid biopsy shows presence of lymphocytic infiltration.

Suppurative thyroiditis is rare and associated with severe anterior neck pain, tenderness, and redness in the region. It is an acute thyroiditis characterized by high fever and a swollen and tender thyroid gland. Lab findings include leukocytosis and increased erythrocyte sedimentation rate (ESR).

De Quervain's thyroiditis, also called subacute granulomatous thyroiditis, is a painful enlargement of the thyroid gland. It is believed to be caused by viral infection or a post-viral inflammatory response. The histological finding in De Quervain's thyroiditis includes the presence of multinucleated giant cell granulomas.
Graves' disease
Explanation
The most likely diagnosis in this patient is Graves' disease.

Thyrotoxicosis occurs due to thyroid hormone excess, the etiology of which varies from Graves' disease, toxic multinodular goiter, toxic adenoma, thyroiditis, and even functioning metastasis.

Symptoms of thyrotoxicosis include hyperactivity, irritability, dysphoria, heat intolerance and sweating, palpitations, fatigue, weakness, weight loss with increased appetite, diarrhea, polyuria, and menstrual irregularities.

Graves' disease is the most common cause of thyrotoxicosis. It is an autoimmune disease in which thyroid-stimulating autoantibodies stimulate thyroid receptors to secrete thyroxine. It is more common in women and can be identified by radionucleotide scan in which the whole thyroid shows increased uptake. Here the patient has all Graves' disease characters: she is middle aged with thyrotoxic characters and her Tc-99 scan shows the characteristic Graves' pattern.

Toxic multinodular goiter is another cause of thyrotoxicosis in which there are multiple nodules that can be felt with palpation, and it is shown to be hot or active with the radionucleotide scan. It shows localized or patchy uptake in the scan pictures.

Hashimoto thyroiditis is an inflammatory condition that follows viral infection. It is associated with a brief period of hyperthyroidism that is followed by hypothyroidism, which may persist throughout life. On Tc scan, it shows decreased uptake.

Factitious hyperthyroidism is due to ingestion of the thyroid hormone. Usually this happens in nurses, physicians, or those who have access to medicine. It can be detected by measuring T3 and T4. There is also decreased uptake on thyroid scan.

Toxic adenoma is a benign neoplastic nodule, which actively secretes thyroxine. It shows localized or patchy uptake of Tc 99 on thyroid scan.
Fatigue, dizziness, salt craving combined with increased pigmentation of her lips and hand creases, as well as hair loss
The correct answer is the combination of fatigue, dizziness, and salt craving with increased pigmentation of her lips and hand creases, as well as hair loss. Addison's disease is the result of adrenal cortex destruction, which causes deficiencies in cortisol, aldosterone, and androgens. Patients can have any combination of various systemic symptoms, including fatigue, weakness, nausea, vomiting, abdominal pain, dizziness, chronic diarrhea, depression, salt craving, and a decreased tolerance for cold. In addition, the physical examination findings can also vary. Some possible findings are hypotension, weight loss, vitiligo, hair loss, and increased pigmentation. The increased pigmentation can occur in the hand creases, dental-gingival margins, buccal and vaginal mucosa, lips, areolas, scars, and pressure points. The increased pigmentation is a result of increased secretion of β-lipoprotein.

The combination of weight gain, decreased libido, and menstrual irregularity with moon facies and increased adipose tissue in neck are indicative of a patient with Cushing's disease. Cushing's disease is essentially the opposite of Addison's disease; its signs and symptoms are caused by an excess of adrenocorticotropin rather than the deficiency seen in Addison's disease. Patients with Cushing's disease can also experience hypertension, hirsutism, depression, easy bruising, muscle weakness, obesity, thin skin, skeletal growth retardation, and acne.

The combination of cramping, numbness around mouth, and tingling in distal extremities with carpopedal spasm and exaggerated deep tendon reflexes could occur in a patient with hypoparathyroidism. This disorder is a result of a deficiency of parathyroid hormone from congenital absence, injury, surgery, or other diseases. Most of the symptoms associated with hypoparathyroidism are a result of hypocalcemia.

The combination of bone pain, flank pain, and anxiety with hypertension and mental confusion could occur in a patient who has hyperparathyroidism. This disorder is characterized as dysfunction in the body's regulatory system for parathyroid hormone. While up to 75% of patients can be asymptomatic, the hypercalcemia associated with hyperparathyroidism can result in the classic complaints of painful bones, renal stones (causing flank pain), abdominal groans, and psychic moans.

The combination of hair loss, decreased energy, and constipation with periorbital puffiness and dry, coarse skin is indicative of hypothyroidism. Hypothyroidism is typically an autoimmune disease or a result of prior radiation therapy or thyroid surgery.