Term
| which cells are found in the central mucoid wedge? lateral wings? |
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Definition
| wedge: corticotrophs, thyrotrophs; lateral wings: lactotrophs, somatotrophs. (gonadotrophs scattered in all 3 areas) |
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Term
| what does vasoactive intestinal polypeptide stimulate the release of (from pituitary)? |
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Definition
| ACTH, FSH/LH, GH, TSH/PRL, PRL |
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Term
| what are the 2 inhibitory hormones that act on the pituitary? |
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Definition
| somatostatin (inhibits GH); dopamine (inhibits PRL) |
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Term
| what is the etiology of pituitary adenomas |
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Definition
| constant stimulation of pituitary gland by trophic hormones of hypothalamus --> cell susceptible for mutations, increased mitogenic response facilitating proliferation of transformed clones into formation of an adenoma (and estrogen is a tumor promoter) |
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Term
| what are the genes responsible for initiating tumorogensis? |
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Definition
| GNAS and its mutant form gsp (mutation and loss of regulation); MEN-1 (mutation and loss of suppression) |
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Term
| what are the genes responsible for promoting tumorogenesis? |
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Definition
| P53, ras, rb, nm-23, cmyc, PTTG, p16 |
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Term
| why is estrogen a tumor promoter |
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Definition
| it induces transcription of target genes that govern cell proliferation |
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Term
| acidophils secrete which hormones |
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Definition
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Term
| basophils secrete which hormones |
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Definition
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Term
| what prolactin level is diagnostic of prolactinoma? |
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Definition
|
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Term
| how do we treat prolactinomas? |
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Definition
| bromocriptine therapy (dopamine agonist) shrinks cells. surgery is ultimate rx |
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Term
| what are acidophil stem cell adenomas? |
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Definition
| secrete PRL and GH, NOT responsive to bromocriptine rx, more aggressive than regular prolactinomas (common in MEN-1 and carney's complex) |
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Term
| overgrowth findings in GH adenomas are initiated by what? |
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Definition
| insulin-like growth factor 1 (hepatic overprod stimulated by excess GH) |
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Term
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Definition
| somatostatin analogues (shrinkage rare), usually surgery is primary tx |
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Term
| truncal obesity, moon facies, buffalo hump, abdominal striae, osteoporosis...? |
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Definition
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Term
| how do we tx cushings disease? |
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Definition
| radiosurgery, drugs, radiotherapy |
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Term
| what is the most common type of pituitary adenoma to present with pituitary apoplexy? |
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Definition
| gonadotropin producing adenoma |
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Term
| how do gonadotropin producing adenomas present? |
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Definition
| usually with mass effect (visual disturbances, headache); less so with endocrine sx (amenorrhea in women, loss of libido in men) - large and invasive tumors |
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|
Term
| how do we tx gonadotropin producing adenomas? |
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Definition
| transphenoidal surgery with adjuvant radiation rx(medical tx not effective) |
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Term
| presentation of non-functioning/null cell adenoma? |
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Definition
| mass effect (large and invasive) tx with surgery + radiation |
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Term
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Definition
| autosomal dominant, caused by mutations in PRKAR1A gene encoding protein kinase A. characterized by CARDIAC (myxoma), ENDOCRINE (GH or prolactin PA), CUTANEOUS (naevi) and NEURAL TUMORS (psammomatous melanotic schwannomas) |
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Term
| what is required to dx pituitary carcinoma? |
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Definition
| CSF or systemic metastasis |
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Term
| metastatic tumors of pituitary most commonly come from which organ? what is the usual clinical presentation? |
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Definition
| breast (then lung), diabetes insipidus and chiasmal compression |
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Term
| what is sheehan's syndrome? |
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Definition
| panhypopituitarism d/t ischemic necrosis of pituitary gland during post-partum period (hypotension following postpartum hemorrhage makes previously enlarged gland of pregnant woman vulnerable to ischemia) |
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Term
| what is pituitary apoplexy? |
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Definition
| extensive, acute hemorrhage (or hemorrhagic necrosis) of pituitary gland or adenoma --> acute onset or worsening of sx (ha, visual impairment, cranial nerve palsies, increased ICP, meningeal signs, coma, sudden death!) |
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Term
| describe what causes lymphocytic hypophysitis and whos affected by it? |
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Definition
| inflam disorder of ant pituitary (autoimmune etiology). assoc with other autoimmune diseases, females during preg or post-partum. enlargement of inflamed pituitary can clinically and radiologically mimic PA --> progressive hypopituitarism |
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|
Term
| what is the tx of lymphocytic hypophysitis? |
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Definition
| steroids, immunosuppressive rx and surgery |
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|
Term
| how do we distinguish between rathke's cleft cyst and PA? |
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Definition
| rathke's is lined by ciliated columnar epithelium and mucous producing goblet cells |
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|
Term
| what is central diabetes insipidus? |
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Definition
| vasopressin/ADH deficiency d/t hypothalamic-posterior pituitary pathologies (polyuria, polydipsia, inappropriately dilute urine) |
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|
Term
| what two hormones stimulate prolactin secretion? |
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Definition
| ESTROGEN and TRH (seratonin in men, therefore antidepressants man elevate prolactin secretion) |
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Term
| what effects do estrogen have on lactation? |
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Definition
| estrogen stimulates prolactin secretion and also increases the number and size of lactotropes and they also block prolactin effects at the level of the breast and prevent lactation during pregnancy (lactation occurs when estradiol levels fall after birth) |
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|
Term
| high levels of prolactin inhibit what? |
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Definition
| pituitary release of gonadotropins and the peripheral effect of gonadotropins on the gonads |
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|
Term
| what secretes inhibin and what is the action of this hormone? |
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Definition
| produced in testes and ovary, inhibits FSH secretion |
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Term
| why do we not see salt craving and hyperkalemia in secondary adrenal insufficiency? why do we not see hyperpigmentation? |
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Definition
| aldosterone secretion is normal because it is primarily regulated by angiotensin, not ACTH; and ACTH levels are not elevated therefore no hyperpig |
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Term
| what is the gold standard test for diagnosing central adrenal insufficiency? |
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Definition
| Insulin Tolerance Test (give insulin and measure cortisol at 0, 30, and 60 min; cortisol >18 mcg/dL = normally functioning hypothalamic-pituitary-adrenal axis. test is adequate if a glucose of <40 mg/dL is achieved) idea: we induce hypoglycemia by giving insulin --> hypoglycemia is a strong stimulus to release ACTH by hypothalamus |
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|
Term
| what morning cortisol level is consistent with dx of adrenal insufficiency? |
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Definition
| <3 mcg/dL (early morning); >18 mcg/dL is evidence of adequate cortisol secretion |
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Term
| what is ACTH stimulation test used for? |
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Definition
| for dx of CHRONIC adrenal insufficiency. give ACTH via IV and measure cortisol at 0, 30, 60 min. cortisol >18 mcg/dL = normal adrenal func. not helpful for acute central adrenal insuff (may take wks-mos after ACTH reduction for adrenal glands to atrophy) |
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Term
| what do we have to keep in mind in interpreting serum cortisol levels in women with estrogen therapy or pregnancy? |
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Definition
| high estrogen --> increase in cortisol binding globulin --> increase in total cortisol levels (normal cortisol level may not indicate adequate cortisol secretion) |
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|
Term
| how does hyperprolactinema cause amenorrhea? |
|
Definition
| increased prolactin --> increased dopamine --> alters endogenous GnRH levels and therefore affects spontaneous LH release. |
|
|
Term
| what effects does hyperprolactinemia have on men? |
|
Definition
| presentation: large tumors, headache, visual sx; causes hypogonadism, decreased libido, impotence, infertility d/t oligospermia |
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|
Term
| how do we approach a patient with hyperprolactinemia? |
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Definition
| r/o preg, meds that increase PRL, hypothyroidism, and renal failure. then do MRI scan |
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Term
| how do we tx people with prolactinomas (macro and micro) |
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Definition
| micro: leave alone and follow; or use bromocriptine if fertility is desired; macro: bromocriptine and surgery if its not shrinking |
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|
Term
| indications for surgery on macroprolactinomas |
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Definition
| inability to tolerate dopamine agonist therapy, unresponsiveness to therapy, increasing tumor size despite medical therapy |
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|
Term
| how do we diagnose acromegaly? |
|
Definition
| oral glucose challenge test --> (should suppress GH) GH level cannot be suppressed below 1 ng/mL |
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Term
| when measuring IGF-1 levels, what are 2 important things to remember? |
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Definition
| 1. serum IGF-1 must be interpreted in light of values in normal sex and age matched subjects 2. IGF1 levels may be lowered in pts with malnutrition and protein insufficiency (consider nutritional status) |
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Term
|
Definition
| 1. surgical removal of adenoma (50% success) --> need multimodality rx 2. radiation (req mos to yrs for radiation to be effective therefore tx with medicine while wait for effects - only for ppl who cant/wont do surg or ppl w/unsuccessful surg) 3. meds (somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) |
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Term
| whats usually the first test performed in people suspected of having cushings syndrome? |
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Definition
| overnight dexamethasone suppression test (1mg given at night, cortisol drawn in morn, cortisol <5mcg/dL r/o cushings, >5mcg/dL --> further testing) |
|
|
Term
| describe alcohol-pseudo-cushings syndrome? |
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Definition
| alcohol abusers have many features suggestive. have elevated levels of usual diurnal variation and fail to suppress with screening overnight dexamethasone suppression test |
|
|
Term
| what do we need for definitive dx of cushings syndrome? |
|
Definition
| show plasma cortisol cannot be suppressed <5mcg/dL w/48 hrs of dexamethasone given in low dose every 6 hours (8 doses). urinary cortisol should fall <30mcg in a 24 hour collection |
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|
Term
| how do we distinguish between cushings disease and other causes of cushings syndrome? |
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Definition
| high-dose dexamethasone suppression test. (2mg q6hx8 doses). pts with CD WILL suppress plasma cortisol to <5mcg/dL, while pts with other causes will fail to suppress. |
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|
Term
| what is the tx for cushings disease? |
|
Definition
| surgical removal (transphenoidal surgery). not cured?--> radiation, gamma knife therapy, bilateral adrenalectomy, med therapy |
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|
Term
| 3 causes of hypotonic polyuria |
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Definition
| 1. primary (excess water intake, normal) 2. hypothalamic (lack vasopressin) 3. nephrogenic (vaspressin levels high, but kidney unresponsive bc of defect in receptor response. can be congenital or caused by electrolyte abn like hypokalemia or hypercalcemia or drugs) |
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|
Term
| how to dx diabetes insipidus |
|
Definition
| standard dehydration test (drink no fluid, record polyuria and weight --> 2 consecutive voided urines differ by <10% osmolality? and pt has lost 2% body weight? --> give 2 mcg desmopressin --> normals will have <5% increase in urine osmolality over next 2 hrs, and pts with DB insipidus will have increase >50%) |
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|
Term
| what are the 3 forms of hereditary diabetes insipidus? |
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Definition
| autosomal dominant central neurogenic diabetes insipidus (many mutations of the vasopressin gene); x-linked nephrogenic db insipidus (abn of the gene for vasopressin V-2 receptor in kidney); autosomal recessive nephrogenic diabetes insipidus (abn of aquaporin-2 water channel) |
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|
Term
| what is essential hypernatremia |
|
Definition
| absence of osmoreceptor input, but intact volume receptor input. excrete excess hypotonic urine and do not sense thirst to replace fluid. dehydration --> vol receptors release vasopressin and pt maintains hypernatremia and concentrated urine |
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Term
| what is triphasic diabetes insipidus? |
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Definition
| after acute injury to neurohypophysis (i.e. trauma) --> section/contusion of posterior pituitary stalk --> disruption of vasopressinergic neurons and decreased release of vasopressin --> db insipidus. THEN disruption of blood flow to posterior pituitary--> necrotic posterior pituitary --> post pituitary releases stored vasopressin in uncontrolled manner --> max anti-diuresis --> hormone depleted --> back to db insipidus |
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|
Term
| how do we tx pts with db insipidus? |
|
Definition
|
|
Term
| how can pts recover from diabetes insipidus alone? |
|
Definition
| hypothalamic db insipidus from trauma or tumor --> hypertrophy of remaining vasopressinergic neurons--> re-establish axons adjacent to capillaries in the hypothalamic suprasellar area |
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