Term
| what does the adrenal cortex produce? |
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Definition
| glomerulosa: mineralocorticoids, fasciculata: glucocorticoids, reticularis: estrogens/androgens |
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Term
| what are most cases of cushing syndrome due to? how is cushing syndrome classified? |
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Definition
| most cases of cushing syndrome are due to exogenous glucocorticoids, but if endogenous, cushing syndrome is divided into ACTH dependent/ACTH independent. cushing disease is when ACTH dependent cushing syndrome directly involves the pituitary. |
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Term
| how does exogenous glucocorticoid administration affect the adrenal cortices? |
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Definition
| exogenous glucocorticoids suppress endogenous glucocorticoids, resulting in *bilateral atrophy of the adrenal cortices |
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Term
| how does increased endogenous glucocorticoid production (cushing syndrome/disease) occur? how does this affect the cortices? |
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Definition
| increased endogenous glucocorticoid production occurs due to increased ACTH production from either a pituitary neoplasm (cushing disease, can be hyperplasia/adenoma/CA), an ectopic adenoma (cushing syndrome, usually neuroendocrine: small cell CA of lung, medullary CA of thyroid, pancreatic tumor, etc), or a primary adrenocortical neoplasm (cushing syndrome, can be hyperplasia/adenoma/CA). either of the first two will lead to increased stimulation of the adrenal glands and subsequent bilateral hyperplasia while the last (primary adrenocortical neoplasm) is just usually a unilateral CA or adenoma. |
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Term
| how do adrenal cortical adenomas appear grossly and histologically? |
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Definition
| grossly: well circumscribed. histologically: clear cytoplasms full of lipid |
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Term
| how does adrenal cortical CA appear grossly and histologically? |
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Definition
| grossly: hemorrhaged, necrotic. histologically: crowded cells w/little cytoplasm, hyperchromatic nuclei, marked pleomorphism, multinucleation, and abnormal mitotic figures. |
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Term
| what is the morphology of a pituitary gland affected by cushing's syndrome? |
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Definition
| crooke's hyaline change: replacement of anterior pituitary cells w/basophilic cells resulting from high levels of endogenous/exogenous glucocorticoids. |
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Term
| what are the clinical features of cushing syndrome? |
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Definition
| cushing syndrome has similar clinical features regardless of the specific etiology: HTN, wt gain, moon face, buffalo hump (deposition of fat subcutaneously near scapulae), truncal obesity, decreased muscle mass in extremities, glucose intolerance, hyperglycemia, glucosuria, polydipsia, cutaneous striae on abdomen, osteoporosis, increased infection risk (excessive steriods), hirsutism, menstrual abnormalities, mental disturbances (depression/difficulty concentrating), and decreased libido. |
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Term
| what lab findings are associated with cushing syndrome? |
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Definition
| increased 24 hr free cortisol and loss of normal diurnal cortisol secretion |
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Term
| how are the different types of cushing syndrome differentiated via lab test? |
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Definition
| cushing disease is *suppressible by high doses of dexamethasone while cushing syndrome due to adrenal hyperplasia/adenoma/CA is not and will have a *low serum ACTH. cushing syndrome due to ectopic ACTH secretion will also *not be suppressible by high doses of dexamethasone. |
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Term
| what is primary hyperaldosteronism due to/characterized by? |
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Definition
| this is usually due to idiopathic bilateral nodular hyperplasia, but may also be due to conn syndrome (single unilateral aldosterone secreting adenoma, more common in women) or glucocorticoid remediable hyperaldosteronism (uncommon, associated w/familial hyperaldosteronism, *ACTH-mediated). primary hyperaldosteronism is characterized by *Na+ retention (HTN), *K+ excretion (hypokalemia), and absence of *elevated renin levels. |
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Term
| what is the morphology of idiopathic bilateral aldosterone secreting hyperplasia? |
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Definition
| marked diffuse and focal hyperplasia |
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Term
| what is the morphology of aldosterone secreting adenomas? |
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Definition
| grossly: generally solitary, small, bright, yellow tumors composed of uniform cells. if treated w/spironolactone, laminated cytoplasmic inclusions called spironolactone bodies may be seen. these adenomas do not suppress ACTH secretion. histologically: clear or pink/granular cytoplasm |
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Term
| what is secondary hyperaldosteronism? |
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Definition
| this occurs when the renin-angiotensin system is activated in the kidney via: arteriolar nephrosclerosis, renal artery stenosis (both = decreased renal perfusion), arterial hypovolemia/edema (causes heart failure, cirrhosis, nephrotic syndrome), and pregnancy (increased estrogen induces increased plasma renin substrate). *all cases of secondary hyperaldosteronism have increased renin levels* |
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Term
| what are the clinical features of hyperaldosteronism? |
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Definition
| HTN (hyperaldosteronism = most common cause of 2ndary HTN), *endothelial dysfunction (decreased levels of G6PD, which reduces endothelial NO synthesis = oxidative stress), CV problems (hypertrophy of L ventricle, arterio/atherosclerosis, and hypokalemia (neuromuscular manifestations, weakness, paresthesias, visual disturbances, and tetany) |
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Term
| how does congenital adrenal hyperplasia result in over secretion of ACTH and androgens? |
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Definition
| CAH (usually due to a defect in 21-hydroxylase) renders the glomerulosa non-responsive to ACTH, so the pituitary tries to compensate by producing even more ACTH, to the point where the reticularis may be stimulated to increase androgen production. |
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Term
| what characterizes adrenocortical insufficiency? what are the different types? |
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Definition
| this form of primary adrenal disease is generally due to decreased stimulation of the adrenal due to ACTH deficiency. patterns include primary acute adrenocortical insufficiency, primary chronic adrenocortical insufficiency (addison's), and secondary adrenocortical insufficiency. |
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Term
| what can cause primary acute adrenocortical insufficiency? |
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Definition
| rapid withdrawal of steroids or failure to increase steroid doses during periods of stress, massive adrenal hemorrhage (eg. newborns after difficult delivery w/trauma+hypoxia), DIC, pts on anti-coagulative therapy, and bacteremic infection (waterhouse-friderichsen syndrome) |
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Term
| what is waterhouse-friderichsen syndrome? |
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Definition
| an overwhelming infection, usually due to *neisseria meningitidis* septicemia, but also can be due to pseudomonas, pneumococci, and haemophilus influenza. clinically it presents as rapidly progressive hypotension/shock, markedly hemorrhagic adrenal glands bilaterally, rash, and DIC. the clinical course is abrupt and devastating and this occurs in children more commonly. |
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Term
| what characterizes primary chronic adrenocortical insufficiency (addison's disease)? causes/presentation? |
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Definition
| causes: autoimmune adrenalitis (irregular shrunken glands), TB/fungi (granulomatous inflammation), or metastatic neoplasms (glands enlarged w/infiltrating neoplasm). clinical presentation: weakness, fatigue, n/v, diarrhea, wt loss, hyperpigmented skin (ACTH precursor stimulates melanocytes), hyperkalemia, hyponatremia, volume depletion, and hypotension |
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Term
| what characterizes pheochromocytoma? |
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Definition
| these well-demarcated, well-vascularized, fibrous tumors most commonly occur in the adrenal medulla of middle age pts and have various degrees of cystic change/necrosis/hemorrhage. they are associated with the "rules of 10"; 10% are malignant, 10% are extra-adrenal (paragangliomas), 10% are b/l, and 10% have severe HTN. the tumors are divided into small nests or "zellballen". |
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Term
| what genetics are associated w/pheochromocytoma? |
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Definition
| 25% of pheochromocytomas have a germline mutation and malignancy risk is increased when succinate dehydrogenase complex subunit genes: SDHB, SDHC, and SDHD are associated. these encode proteins involved in mitochondrial electron transport/O2 sensing and their loss of function may cause stabilization of the oncogenic transcription factor HIF1 alpha (hypoxia-inducible factor) and induce tumor genesis. |
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Term
| why is it difficult to determine pheochromocytoma malignancy? |
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Definition
| there is no histologic feature that reliably predicts clinical behavior - but increased risk of metastases/aggressive behavior may be indicated by increased mitoses, necrosis, and spindle cell morphology. some tumors that look benign may metastasize and some which look malignant may not. therefore, *dx of malignancy is based exclusively on presence of metastasis* |
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Term
| what are the clinical features of pheochromocytoma? |
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Definition
| HTN, tachycardia, headaches, MI, stroke, and increased urinary excretion of vanillylmandelic acid (VMA) |
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Term
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Definition
| these are similar to pheochromocytoma, as 90% secrete catecholamines, but they affect mainly children < 5 y/o and metastasize earlier and wider spread. they may also produce some urinary VMAs. these appear in the adrenal medulla or in the adjacent retroperitoneal area (posterior mediastinum: 2nd most common location). |
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Term
| what characterizes neuroblastomas grossly/histologically? |
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Definition
| grossly: large, soft, necrotic, hemorrhaging. histologically: small cells in solid sheets/small nests and *homer-wright pseudorosettes (cells gather around tangled eosinophilic fibrils). |
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Term
| what are the MEN syndromes? |
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Definition
| MEN1/wermer syndrome, MEN 2/2a, MEN 3/2b |
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Term
| what characterizes MEN1? clinical manifestations? |
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Definition
| MEN1/wermer syndrome is due to a germline mutation of the MEN1 tumor suppressor gene which encodes for menin. it is called "multiple endocrine neoplasia" neoplasia b/c it involves the parathyroid (hyperplasia, adenomas), pancreas (tumors such as gastrinomas, insulinomas, and microadenomas), and pituitary (prolactinomas/somatotrophin secreting tumors). clinical manifestations: hypoglycemia (insulinoma), peptic ulcers (gastrinoma), nephrolithiasis (varying degrees). |
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Term
| what characterizes MEN 2/2a? |
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Definition
| aka sipple syndrome, this is linked to the RET proto-oncogene and is associated w/pheochromocytoma, medullary thyroid CA, and parathyroid hyperplasia |
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Term
| what characterizes MEN 3/2b? |
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Definition
| this is also associated w/medullary CA of the thyroid and pheochromocytomas, but NOT primary hyperthyroidism. this also is associated w/gangiolneuromas of the skin, respiratory tract, and GI and a marfanoid habitus (tall, long arms, spindly features) |
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