Term
| what are the hypothalamic hormones? what is the pattern to their secretion? |
|
Definition
| CRH, CCK, and ADH (AVP) - which are all secreted diurnally, with midnight being the peak of the pulsatile secretion |
|
|
Term
| how can the hypothalamic hormones affect the anterior pituitary? how is this regulated? |
|
Definition
| the hypothalamic hormones can simultaneously act upon the anterior pituitary to stimulate ACTH secretion w/the predominant influence of CRH. this is then regulated by glucocorticoid production, which provides negative feedback for ACTH production (this is the *only steroid hormone w/influence on ACTH secretion*). |
|
|
Term
| how big of a molecule is ACTH? |
|
Definition
| 39 AA, only ~35 of which are necessary for 90% of biologic function |
|
|
Term
| what are the 3 zones in the adrenal cortex? |
|
Definition
| zona glomerulosa (mineralocorticoids such as aldosterone), fasciculata (glucocorticoids), and reticularis (androgens) |
|
|
Term
| what are the embryologic origins of the 2 main adrenal gland components? |
|
Definition
| cortex: mesoderm, medulla: ectoderm |
|
|
Term
| what does the adrenal medulla produce? |
|
Definition
| catecholamines from chromaffin cells |
|
|
Term
| what is florinef/fludrocortisone? |
|
Definition
| a synthetic analog of aldosterone which has a longer half life (aldosterone's half life is very short) |
|
|
Term
| what are the medicinal benefits of glucocorticoid administration? |
|
Definition
| anti-inflammatory and immunosuppression |
|
|
Term
| what ADRs are associated with glucorticoids? |
|
Definition
| *enhanced gluconeogenesis: creates gluconeogenesis - can lead to DM. *antagonization of glucose: inhibition of glucose uptake in insulin sensitive cells (esp muscle), which can cause hyperglycemia. *catabolism of protein: collagen in skin is broken down = striae. |
|
|
Term
| what is the only steroid hormone w/the ability to suppress ACTH secretion? |
|
Definition
| cortisol, which dexamethasone is similar to - which is why the test for cushing's disease works. |
|
|
Term
| how does cortisol travel in the bloodstream? |
|
Definition
| cortisol is bound to cortisol binding globulin (CBG), which is predominantly made in the liver. when the body needs cortisol, it can unbind some = free cortisol, which can be detected w/a 24 hr urine assay. |
|
|
Term
| what is the normal daily secretion rate for cortisol? |
|
Definition
| 30 mg/day (but diurnally) |
|
|
Term
| what is the "early depression" seen in cushing's disease? late depression? |
|
Definition
| early depression: increased ACTH secretion, resulting in higher cortisol levels which still provide sufficient negative feedback on anterior pituitary (ACTH) and hypothalamus (CRH). late depression is a more advanced version of the same situation. |
|
|
Term
| what characterizes cushing's disease? |
|
Definition
| hyperplasia/adenoma/CA produces high ACTH levels (50-100, normal:5-30), but cortisol is still able to provide some feedback - the set point is just higher (HPA axis is still intact). |
|
|
Term
| what is the dexamethasone test? |
|
Definition
| dexamethasone is a synthetic glucocorticoid which should suppress ACTH production and thus cortisol production (but doesn't interfere w/accurate cortisol levels). usually it is administered 1 mg around 11 pm and then cortisol levels should be <5 in the morning. if they are not, additional testing is necessary. |
|
|
Term
| what does it mean to say that cushing's pts have central obesity? |
|
Definition
| fat distribution in cushing's pts is seen predominately in the abdomen/thorax/*supraclavicular area*/buffalo hump. |
|
|
Term
| what are the gynecologic effects of cushings? |
|
Definition
| amenorrhea, due to cortisol levels suppressing gonadotrophins (LH, FSH) |
|
|
Term
| what are the cardiovascular effects of cushings? |
|
Definition
| increased BP as cortisol can increase aldosterone |
|
|
Term
| what are the musculoskeletal effects of cushings? |
|
Definition
| steroid myopathy - proximal muscles become weak/fatigued w/minimal strain |
|
|
Term
| what are the neuro/psychiatric effects of cushings? |
|
Definition
|
|
Term
| what are the dermatologic effects of cushings? |
|
Definition
| collagen catabolism leads to striae formation, superficial veins, reddish hue, and specifically: violaceous striae (purple stretch marks). facial plethora (red fullness from collagen destruction), hirsutism (possible increase in adrenal androgens), and acne are also possible. |
|
|
Term
| what is cushingoid habitus? |
|
Definition
| someone who has cushings-like features, but no formal diagnosis |
|
|
Term
| what is cushingoid syndrome? |
|
Definition
| abnormally high cortisol levels and cushingoid features |
|
|
Term
| what is cushings disease? |
|
Definition
| cushings syndrome due to a pituitary tumor |
|
|
Term
| what is ectopic cushings? |
|
Definition
| ACTH/CRH production from tumors in other areas outside the brain (lungs etc) |
|
|
Term
| how did harvey cushing originally discover the disease? |
|
Definition
|
|
Term
| what is the sequence of tests dr. F runs to dx cushings? |
|
Definition
| *overnight 1 mg dexamethasone screening test, which if cortisol levels are still high (> 5) after, then a *low dose test is run. .5 mg dexamethasone is then administered every 6 hrs for 2 days to r/o any possible overnight test false positives. if the pts cortisol is still not suppressed (through negative feedback on ACTH), then the *high dose test is performed - where 2 mg dexamethasone is administered which should suppress the cortisol (if cushing's disease). |
|
|
Term
| what are other lab studies for cushings disease? |
|
Definition
| elevated blood glucose (DM common in these pts), hypercalciuria (kidney stones), hypokalemia (chloride resistant type - hard to tx), erythrocytosis (increased RBC production), and eosinopenia (reduced eosinophils) |
|
|
Term
| what is petrosal sinus testing? |
|
Definition
| this is performed when there is lab and imaging evidence of a pituitary tumor, but no dexamethasone suppression at high dose. |
|
|
Term
| what is it called if a pt has no difference in cortisol levels between morning and evening? what tests should be run if this is found in a pt? |
|
Definition
| loss of diurnal variation, which is an early finding of cushings syndrome. (cortisol should be higher in the morning). cortisol level, 24 hr urine free cortisol, and overnight dexamethasone test. |
|
|
Term
| can exogenous steroids cause some of the physical characteristics associated w/cushings? |
|
Definition
| yes, exogenous steroids can cause violaceous striae etc |
|
|
Term
| can exogenous steroids cause some of the physical characteristics associated w/cushings? |
|
Definition
| yes, exogenous steroids can cause violaceous striae etc - need to ask pts if they are on/have been on steroids. |
|
|
Term
| can cushings occur in newborns? |
|
Definition
| yes, who may have moon face, central obesity, and/or ambiguous genitalia. |
|
|
Term
| what characterizes ACTH-independent cushings syndrome? |
|
Definition
| adrenal hyperplasia/adenoma/CA can make excess cortisol and are *not under the influence of ACTH (ACTH levels are very low ~5). pts w/this kind of ACTH-independent cushings syndrome may present differently than the classic cushings disease, potentially as wt gain for adenoma and metabolic abnormalities/protein wasting for CA (more aggressive). *high dose dexamethasone test will not suppress cushings due to adrenal hyperplasia/adenoma/CA. |
|
|
Term
| what characterizes ectopic cushings? |
|
Definition
| ectopic ACTH-producing adenomas/CA (often in the lungs) do not suppress with any dexamethasone tests like adrenal hyperplasia/adenoma/CA - BUT they have much higher ACTH serum levels (vs ACTH-independent tumors) and can cause hyperpigmentation of the skin (due to melanocyte stimulating hormones/MSH - a molecule related to ACTH). |
|
|
Term
| what are the 4 most common ectopic ACTH-producing tumors? |
|
Definition
| lung CA, lung adenomas, pancreatic CA, and thymoma |
|
|
Term
| what is treatment for cushing's disease? |
|
Definition
| stereoscopic pituitary hypophysectomy - allows tumor to be resected and still preserve pituitary tissue/retain functionality of the gland. if no response, possibly a b/l adrenalectomy. |
|
|
Term
| what is nelson's syndrome? |
|
Definition
| a possible consequence of a b/l adrenalectomy - which initially leads to unopposed ACTH secretion (along w/anything else cortisol inhibits). *nelson's syndrome occurs if the pituitary then develops an ACTH secreting tumor often along with hyperpigmentation (POMC, MSH). this is then treated with surgery directed at the pituitary gland. |
|
|
Term
| what can be used for cushing's pts who fail sx or are not candidates? |
|
Definition
| adrenalytic agent such as mitotane (destroys adrenals) or radiation |
|
|
Term
| what is an "incidentaloma"? |
|
Definition
| a non-secreting adrenal adenoma found incidentally in imaging for some other pathology - these are not removed unless over 3 cm |
|
|
Term
| what are the manifestations of a cortisol deficiency? usual etiology? |
|
Definition
| manifestations are vague: n/v, anorexia, diminished vigor, etc. etiology is usually lack of HPA axis recovery due to steroid administration. |
|
|
Term
| what are the manifestations of aldosterone deficiency? |
|
Definition
| significant hypotension, shock, wt loss - due to an inability to retain salt+water in the kidneys. salt cravings may occur. |
|
|
Term
| what is addison's disease? (*should know stars*) |
|
Definition
| an autoimmune disease where Ab are directed at the adrenal cortex, affecting synthesis+release of glucocorticoid/mineralocorticoid w/varying degrees of adrenal suppression. pts w/this may have *hypotension (shock), *hyperpigmentation (increased ACTH/MSH), *hyponatremia, *hyperkalemia, and positive anti-adrenal Ab. |
|
|
Term
| how are pts w/adrenal insufficiency treated? |
|
Definition
| immediately treat dehydration/Na+ loss (normal saline), then do rapid ACTH stimulation test (give them ACTH to see if they can make cortisol) along w/dexamethasone (won't throw off cortisol levels, but will help condition), then hydrocortisone, then synthetic mineralocorticoid (b/c only high dose glucocorticoid also has mineralocorticoid effects). |
|
|
Term
| what is adrenal crisis? tx? |
|
Definition
| adrenal crisis: 8-10 L dry. tx acute condition, then start maintenance dosage of hydrocortisone/fludrocortisone. |
|
|
Term
| what is the most common form of adrenal insufficiency? |
|
Definition
|
|
Term
| what characterizes a 21-hydroxylase deficiency? |
|
Definition
| 21-hydroxylase is responsible for synthesizing cortisol and aldosterone, so pts w/this will look like addison's pts - but will have *increased adrenal androgen (ACTH overcompensation) which can cause hirsutism/amenorrhea along w/the hypotension, salt wasting and hyperpigmentation. this may be congenital or appear during pregnancy. |
|
|
Term
| what characterizes an 11-hydroxylase deficiency? |
|
Definition
| this is less common and involves an enzymatic block which results in an *aldosterone/cortisol reduction* but *production of DOC = HTN*. |
|
|
Term
| what is conn's syndrome? tx? |
|
Definition
| a unilateral adrenal adenoma which produces excessive aldosterone = *hypokalemia, metabolic alkalosis (high CO2), and *HTN. tx: sx |
|
|
Term
| what is adrenal hyperplasia? tx? |
|
Definition
| similar to conn syndrome, but bilateral, so tx has to be aldosterone antagonists rather than sx (don't want to remove adrenal glands unless you have to). |
|
|
