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Condition in which both cortisol and ACTH are elevated
Secondary Cushing's [due to pituitary adenoma]
Conditions that cause hyperadrenocorticism with decreased ACTH
Primary Cushing [due to adrenal hyperplasia] and Tertiary Cushing [neoplasia, eg small cell]
The most common Cushing etiology. What are the culprits? What's the effect on ACTH?
-Chronic steroid use, asthma meds, prednisone.
-All decrease ACTH by negative feedback.
Dexamethasone suppression test results in healthy patients.
Decreased cortisol after low [or high] dose.
Dexamethasone suppression test results in ACTH-producing pituitary adenoma [secondary Cushing}
Cortisol does not decrease after low dose, does decrease after high dose
Dexamethasone suppression test results in adrenal cortex adenoma [primary Cushing] and ACTH-releasing tumor [tertiary Cushing]
Cortisol does not decrease after low dose or high dose
Most common single gene defect, pattern of inheritance, and hallmarks.
-Neurofibromatosis-1 (Von Recklinghausen syndrome)
-Neural fibromas, Cafe au lait spots, Axillary/inguinal freckles, Optic nerve glioma, Lisch nodules [on iris]
HTN, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia, skin changes, osteoporosis, amenorrhea and immune suppression
Primary hyperaldosteronism hallmark characteristics
-Aldosterone secreting tumor [glomerulosa region],
-HTN, hypokalemia, metabolic alkalosis [swap H+ to replace K+], and low plasma renin
Low blood volume or BP [e.g., CHF, cirrhosis, dehydration, renal artery stenosis, renal failure]. Results in overactive RAAS & high plasma renin
Secondary hyperaldosteronism etiology and results
Primary hyperaldosteronism treatment
Spironolactone [aldosterone antagonist diuretic] or amiloride [K-sparing diuretic]
Primary adrenal insufficiency name.
-Addison's, resulting in [hypocortiolism and] hypoaldosteronism.
-[Cortisol and] aldosterone low. Hypoglycemia, hypotension, hyperkalemia and bronzing.
Secondary adrenal insufficiency cause & findings
-Insufficient ACTH from anterior pituitary.
-Mimics Addisons' but no bronzing and no hyperkalemia.
Waterhouse-Friderichsen syndrome findings and etiology
Acute adrenocortical insufficiency due to adrenal hemorrhage. Associated with meningococcal septicemia
Sheehan's syndrome findings and etiology
Postpartum hypopituitarism. Enlargement of anterior pitutary during pregnancy without corresponding increase in blood supply leads to infarction of the pituitary gland following severe bleeding during delivery.
Sheehan's syndrome hallmark symptoms [post- partum hypopituitarism]
Amenorrhea, poor lactation, loss of pubic and axillary hair, fatigue
Most common tumor of the adrenal medulla in adults. From what tissue is it derived?
-Derived from chromaffin cells that arise from neural crest.
10% malignant, 10% bilateral, 10% extra-adrenal, 10% calcify, 10% kids, 10% familial
Pheochromocytoma tumor products
Epinephrine, Norepinephrine and Dopamine; can cause episodic hypertension, flushing, palpitations
Pheochromocytoma diagnostic labs
24-hr urinary VMA (vanillylmandelic acid) and plasma catecholamines.
Alpha blockers, especially phenoxybenzamine [nonselective, irreversible alpha blocker] "Pheo-Knocks-Ben's Amine"
The two episodic hyperadrenergic disorders and their symptoms
Carcinoid tumors & pheochromocytoma. Hypertension [blood Pressure], Pain, Perspiration, Palpitations, Pallor
Most common tumor of adrenal medulla in kids. Where else may it occur? What lab helps to diagnose?
-Anywhere along the Sympathetic chain.
-24-hr HVA in urine.
MEN 1 [Multiple Endocrine Neoplasia 1] = Werner's syndrome mnemonic and tumor sites
Pancreas tumors [Z-E syndrome, insulinomas]; Pituitary tumors [prolactin or GH]; Parathyroid tumors [hypercalcemia]
MEN 1 (Multiple Endocrine Neoplasia) tumor sites & presentation
Pituitary [prolactinoma], parathyroid [secretes PTH] & pancreas [gastrinoma or insulinoma].
MEN2A (Multiple Endocrine Neoplasia 2A) (Sipple's syndrome) mnemonic and tumor sites
Pheochromocytoma, Parathyroid tumor, and Medullary thyroid carcinoma [secretes calcitonin]
MEN 2B mnemonic and tumor sites
Medullary thyroid carcinoma [secretes calcitonin], Marfanoid appearance, Pheochromocytoma. May also have oral/intestinal ganglioneuromas.
Cold intolerance, hypoactivity, weight gain, fatigue, decreased appetite, constipation, weakness, decreased reflexes, dry cool skin, corase brittle hair
Primary hypothyroidism labs
Elevated TSH, decreased total T4, decreased free T4, decreased T3 uptake
Hyperthyroidism signs & symptoms
Heat intolerance, hyperactivity, weight loss, palpitations, arrhythmias, diarrhea, exophthalmos, warm moist skin, fine hair
Primary hyperthyroidism name and labs
-Graves, thyroid adenoma
-Decreased TSH, increased total T4, & free T4, increased T3 uptake
Grave's disease etiology and hallmark characteristics.
-Autoimmune hyperthyroidism with thyroid-stimulating TSH receptor antibodies.
-Exophthalmia, pretibial myxedema, diffuse goiter. Often presents during stress.
Hashimoto's thyroiditis hallmark charateristics
-Autoimmune hypothyroidism. Moderately enlarged, nontender thyroid produces anti-thyroglobulin antibodies.
Subacute thyroiditis [de Quervain's] symptoms & diagnosis
Self-limited hypothyroidism often following a flulike illness. Elevated ESR, jaw pain, tender thyroid. Granulomatous inflammation.
Thyroid replaced by fibrous tissue. Presents with fixed, hard, painless goiter.
Stress-induced thyrotoxicosis with high fever, cardiovascular and nervous system dysfunction. Possible death by arrhythmia.
Thyroid storm & Grave's disease
Cause: Iodine deprivation followed by iodine restoration. Causes release of T3 and T4. Non malignant.
Toxic multinodular goiter causes & appearance
Papillary thyroid carcinoma frequency, prognosis, and presentation
-Most common thyroid cancer [>80%]
-Ground glass nuclei, "Orphan Annie eyes"[Daddy Warbucks=Papa-larry] and psamomma [Papa & Momma] bodies, nuclear grooves, increased risk with childhood irradiation.
Follicular carcinoma frequency, prognosis and presentation
Second most common thyroid cancer. [~9-15%]
-Uniform follicles form asymptomatic nodule. Mets to bone and lung occur in 15% . Do CXR, bone scan.
Medullary carcinoma frequency, prognosis and presentation
-Thyroid cancer of parafollicular "C" cells. [Produces calcitonin]. Lump at base of neck that may cause hoarseness or dysphagia.
-25% of cases are associated with MEN types 2A and 2B.
The most rare of thyroid carcinomas and the population affected, prognosis.
-Undifferentiated/anaplastic thyroid cancer
-Older patients, very poor prognosis.
Due to severe fetal hypothyroidism. May be due to endemic lack of iodine, defect in T4 formation, or development failure in thyroid formation.
Acromegaly etiology, signs & symptoms
-Excess GH in adults
-Large tongue with deep furrows, deep voice, large hands and feet, coarse facial features, impaired glucose tolerance [insulin resistance]
Acromegaly diagnostic tests
-Increased serum IGF-1
-Failure to suppress serum GH following oral glucose tolerance test
1. Parathyroid adenoma increases PTH
2. Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia. Classic presentation includes weakness and constipation with "stones, bones, and groans"
Primary hyper-parathyroidism cause & signs & symptoms
Cystic bone spaces filled with brown fibrous tissue, found in primary hyperparathyroidism
Osteitis fibrosa cystica (von Recklinghausen's syndrome)
1. Hypocalcemia from decreased Ca absorption in chronic renal failure --> stimulus of parathyroids --> hyperphosphatemia. Ends in osteodystrophy
2. Squamous cell lung cancer [paraneoplastic secretion of PTH]
Secondary hyperparathyroidism symptoms & causes
Bone lesions due to secondary hyperparathyroidism in end-stage renal disease. Hyperphosphatemia and hypocalcemia.
Causes: Surgical excision, autoimmune destruction, or DiGeorge syndrome. Effects: Hypocalcemia, tetany.
Hypoparathyroidism causes & effects
Found in hypoparathyroidism. "Tetany-on-demand." Tap CN-7 [facial nerve] --> contraction of facial muscles.
Chvostek's sign from hypocalcemia
Found in hypoparathyroidism. Occlusion of brachial artery with BP cuff --> carpal spasm
Trousseau's sign-- hypocalcemia
AD kidney unresponsiveness to PTH. Hypocalcemia, shortened 4th/5th digits, short stature
Ca2+ ingestion, Parathyroid tumor, Hyperparathyroidism, Squamous cell lung cancer, Thiazide diuretics, Lithium use, Paget's, Addison's, Z-E, Excess vit D.
All are causes of hypercalcemia--"bones, groans, stones"
Prolactinoma. Dopamine agonists [bromocriptine & cabergoline] cause shrinkage. Tumor may impinge on optic chiasm --> temporal hemianopia
Common pituitary adenoma & its treatment
Polydipsia, polyphagia, weight loss, DKA (type I), hyperosmolar coma (type 2), unopposed secretion of GH and epi (exacerbating hyperglycemia)
Acute manifestations of DM
Small vessel diease (diffuse thickening of BM) --> retinopathy, glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN, Kimmelsteil-Wilson nodules). Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease and gangrene, cerebrovascular disease.
Chronic manifestations of DM due to nonenzymatic glycosylation
Neuropathy [motor, sensory and autonomic dysfunction]; and cataracts [sorbitol accumulation]
Chronic manifestations of DM due to osmotic damage
Juvenile onset, due to viral or immune destruction of beta cells. Always require insulin. Genetic predisposition. Ketoacidosis is common. Polyuria, polydipsia, weight loss.
Type I DM
Adult onset. Increased resistance to insulin. Insulin is sometimes neccessary in tx. Age is >40y at onset. Strong polygenic genetic predisposition. No association with HLA. Mild to moderate glucose intolderance. Ketoacidosis is rare. Beta cell numbers in islets are variable, serum insulin levels are variable. poly sx & weight loss occur sometimes.
Type II DM
One of most important complications of Type I DM. Usually due to increased insulin requirements from increased stress (eg infection). Excess fat breakdown and increased ketogenesis from increased FFAs which are then made into ketone bodies.
Kussmaul respirations (rapid/deep breathing), N/V, abd pain, psychosis, dehydration, fruity breath
DKA signs and sx
Hyperglycemia, acidosis, decreased HCO3- (anion gap), increased blood ketone levels, leukocytosis, hyperkalemia but depleted intracellular K due to transcellular shift.
DKA (diabetic ketoacidosis) labs
Complications: Life-threatening mucormycosis, cerebral edema, cardiac arrhythmias, heart failure
Monitor/adjust fluids, insulin, K+ [to replace intracellular stores]; glucose if neccessary to prevent hypoglycemia
Intense thirst and polyuria together with an inability to concentrate urine owing to lack of ADH (central) or to a lack of renal response (nephrogenic)
Hereditary or secondary to hypercalcemia, lithium, demeclocycline [ADH antagonist]
Causes of nephrogenic diabetes insipidus
H2O deprivation test - urine osmolality unaffected [remains very low]. Response to desmopressin distinguishes central type [responds] from nephrogenic type [no response].
Diabetes insipidus diagnosis
ALL: Adequate fluid intake. Central: intranasal desmopressin (ADH analog). Nephrogenic: diuretics (Hydrochlorothiazide or amiloride)
Diabetes insipidus treatment
Excessive water retention, hyponatremia[Na is diluted by reabsorbed H2O], urine osmolarity > serum osmolarity
SIADH signs & symptoms
Complication : Extreme hyponatremia [central pontine myelinolysis]. Can lead to seizures [correct slowly!]
Most dangerous SIADH complication
Water restriction, then Demeclocycline [a tetracycline derivative!]; add furosemide in severe cases. Never correct Na faster than 10 mEq in 24 hr!
Ectopic ADH [small cell lung cancer], CNS disorders/head trauma; pulmonary disease [pneumonia, TB]; or drugs [cyclophosphamide]
Tumors of neuroendocrine cells in gut and in lungs . Secrete high levels of 5-HT (serotonin). Paroxysmal flushing, wheezing asthma, diarrhea & RCHF
Carcinoid syndrome causes, signs & symptoms
5-HT (serotonin) undergoes first-pass metabolism in liver
Reason why carcinoid syndrome is not seen in primary GI tumors
Diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease.
Carcinoid syndrome signs & symptoms
Gastrin-secreting tumor of pancreas. Causes recurrent ulcers. May be associated with MEN type I
Parathyroid [hypercalcemia], pituitary medulla [calcitonin], pancreas [gastrinoma--> ulcers-Zollinger Ellison]
MEN-1 tumor sites
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