Example and explanation of tumors that cause Cushing's
Small cell lung cancer. Ectopic ACTH production
Chronic steroid use, asthma meds & prednisone. All decrease ACTH by negative feedback. [Most common Cushing etiology.]
DST test with ACTH-producing pituitary adenoma (Cushing's)
Cortisol does not decrease after low dose, does decrease after high dose
Neurofibromatosis-1 (Von Recklinghausen syndrome)
Most common 1-gene defect, an autosomal dominant causing neural fibromas & cafe au lait spots
DST results in patient w/ cortisol producing [adrenal] tumor or patient w/ ectopic ACTH-tumor
Cortisol does not decrease after low dose or high dose
HTN, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia, skin changes, osteoporosis, amenorrhea and immune suppression
Primary hyperaldosteronism etiology & diagnosis
Aldosterone secreting tumor [glomerulosa], resulting in HTN, hypokalemia, metabolic alkalosis, and low plasma renin
Secondary hyperaldosteronism etiology and results
Low blood volume [e.g., CHF, cirrhosis, dehydration, renal artery stenosis, renal failure]. Results in overactive RAAS & high plasma renin
Addison's disease cause & findings
Primary adrenal insufficiency, cortisol and aldosterone low. Hypoglycemia, hypotension, hyperkalemia and bronzing.
Secondary adrenal insufficiency
Insufficient ACTH. Mimics Addisons' but no bronzing and no hyperkalemia.
Waterhouse-Friderichsen syndrome findings & bacterial cause
Acute adrenocortical insufficiency due to adrenal hemorrhage. Associated with meningococcal septicemia
Postpartum hypopituitarism. Enlargement of anterior pitutary during pregnancy without corresponding increase in blood supply leads to increased risk of infarction of the pituitary gland following severe bleeding during delivery.
Sheehan's syndrome symptoms [post- partum hypopituitarism]
Fatigue, amenorrhea, poor lactation, loss of pubic and axillary hair
10% malignant, 10% bilateral, 10% extra-adrenal, 10% calcify, 10% kids, 10% familial
Most common tumor of the adrenal medulla in adults. Derived from chromaffin cells which arise from neural crest.
Epinephrine, Norepinephrine and Dopamine; can cause episodic hypertension.
Alpha blockers, especially phenoxybenzamine [nonselective, irreversible alpha blocker] "Pheo-Knocks-Ben's Amine"
Episodic hyperadrenergic causes and symptoms
Carcinoid tumors & pheochromocytoma. Hypertension [Pressure], Pain, Perspiration, Palpitations, Pallor
Most common tumor of adrenal medulla in kids. Can occur anywhere along the sympathetic chain. See HVA (DA breakdown product) in urine. N-myc oncogene.
MEN 1 [Multiple Endocrine Neoplasia 1] = Werner's syndrome characteristics
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 [hypercalcemia] & pancreas [gastrinoma]. "Stones, bones & groans"
MEN2A (Multiple Endocrine Neoplasia 2A) (Sipple's syndrome)
Medullary thyroid carcinoma , Pheochromocytoma, Parathyroid tumors [but not oral ganglioneuromas, as MEN2B does]
MEN 2B traits & dx
Medullary thyroid carcinoma [secretes calcitonin], Pheochromocytoma, Oral/intestinal ganglioneuromas. Marfan appearance.
Cold intolerance, hypoactivity, weight gain, fatigue, decreased appetite, constipation, weakness, decreased reflexes, dry cool skin, corase brittle hair
Primary hypothyroidism labs
Increased 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 labs (Graves, thyroid adenoma)
Decreased TSH, increased total T4, & free T4, increased T3 uptake
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.
Autoimmune hyperthyroidism with thyroid-stimulating TSH receptor antibodies. Exophthalmia, pretibial myxedema, diffuse goiter. Often presents during stress.
Thyroid storm & Grave's disease
Stress-induced thyrotoxicosis with high fever, cardiovascular and nervous system dysfunction. Possible death by arrhythmia.
Toxic multinodular goiter causes & appearance
Cause: Iodine deprivation followed by iodine restoration. Causes release of T3 and T4. Non malignant.
Papillary thyroid carcinoma frequency & diagnosis
Most common thyroid cancer. Good prognosis. Ground glass nuclei, "Orphan Annie eyes"[Daddy Warbucks=Papa-lary] and psamomma [Papa & Momma] bodies, nuclear grooves, increased risk with childhood irradiation.
Thyroid cancer of parafollicular "C" cells. Produces calcitonin. Sheets of cells in amyloid stroma. Associated with MEN types 2A and 2B.
Due to severe fetal hypothyroidism. May be due to endemic lack of iodine, defect in T4 formation, or development failure in thyroid formation.
Acromegaly signs & symptoms
Large tongue with deep furrows, deep voice, large hands and feet, coarse facial features, impaired glucose tolerance [insulin resistance]
Increased serum IGF-1; failure to suppress serum GH following oral glucose tolerance test
Primary hyper-parathyroidism cause & signs & symptoms
1. Parathyroid adenoma increases PTH
2. Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia. Classic presentation includes weakness and constipation with "stones, bones, and groans"
Osteitis fibrosa cystica (von Recklinghausen's syndrome)
Cystic bone spaces filled with brown fibrous tissue, found in primary hyperparathyroidism
Secondary hyperparathyroidism symptoms & causes
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]
Bone lesions due to secondary hyperparathyroidism in end-stage renal disease. Hyperphosphatemia and hypocalcemia.
Hypoparathyroidism causes & effects
Causes: Surgical excision, autoimmune destruction, or DiGeorge syndrome. Effects: Hypocalcemia, tetany.
Chvostek's sign from hypocalcemia
Found in hypoparathyroidism. "Tetany-on-demand." Tap CN-7 [facial nerve] --> contraction of facial muscles.
Trousseau's sign-- hypocalcemia
Found in hypoparathyroidism. Occlusion of brachial artery with BP cuff --> carpal spasm
AD kidney unresponsiveness to PTH. Hypocalcemia, shortened 4th/5th digits, short stature
All are causes of hypercalcemia--"bones, groans, stones"
Ca2+ ingestion, Parathyroid tumor, Hyperparathyroidism, Squamous cell lung cancer, Thiazide diuretics, Lithium use, Paget's, Addison's, Z-E, Excess vit D.
Common pituitary adenoma & its treatment
Prolactinoma. Dopamine agonists [bromocriptine & cabergoline] cause shrinkage. Tumor may impinge on optic chiasm --> temporal hemianopia
Acute manifestations of DM
Polydipsia, polyphagia, weight loss, DKA (type I), hyperosmolar coma (type 2), unopposed secretion of GH and epi (exacerbating hyperglycemia)
Chronic manifestations of DM due to nonenzymatic glycosylation
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 osmotic damage
Neuropathy [motor, sensory and autonomic dysfunction]; and cataracts [sorbitol accumulation]
Type I DM
Juvenile onset, due to viral or immune destruction of beta cells. Always require insulin. Genetic predisposition. Ketoacidosis is common. Polyuria, polydipsia, weight loss.
Type II 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.
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.
DKA signs and sx
Kussmaul respirations (rapid/deep breathing), N/V, abd pain, psychosis, dehydration, fruity breath
DKA (diabetic ketoacidosis) labs
Hyperglycemia, acidosis, decreased HCO3- (anion gap), increased blood ketone levels, leukocytosis, hyperkalemia but depleted intracellular K due to transcellular shift.
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)
Causes of nephrogenic diabetes insipidus
Hereditary or secondary to hypercalcemia, lithium, demeclocycline [ADH antagonist]
Diabetes insipidus diagnosis
H2O deprivation test - urine osmolality unaffected [remains very low]. Response to desmopressin distinguishes central type [responds] from nephrogenic type [no response].
Diabetes insipidus treatment
ALL: Adequate fluid intake. Central: intranasal desmopressin (ADH analog). Nephrogenic: diuretics (Hydrochlorothiazide or amiloride)
SIADH signs & symptoms
Excessive water retention, hyponatremia[Na is diluted by reabsorbed H2O], urine osmolarity > serum osmolarity
Most dangerous SIADH complication
Complication : Extreme hyponatremia [central pontine myelinolysis]. Can lead to seizures [correct slowly!]
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]
Carcinoid syndrome causes, signs & symptoms
Tumors of neuroendocrine cells in gut and in lungs . Secrete high levels of 5-HT (serotonin). Paroxysmal flushing, wheezing asthma, diarrhea & RCHF
Reason why carcinoid syndrome is not seen in primary GI tumors
5-HT (serotonin) undergoes first-pass metabolism in liver
Carcinoid syndrome signs & symptoms
Diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease.
Gastrin-secreting tumor of pancreas. Causes recurrent ulcers. May be associated with MEN type I
MEN-1 tumor sites
Parathyroid [hypercalcemia], pituitary medulla [calcitonin], pancreas [gastrinoma--> ulcers-Zollinger Ellison]