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66 Cards in this Set
- Front
- Back
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adrenal glands where are they located? what is it derived from? |
suprarenal glands located above kidney in retroperitoneal
cortex derived from mesoderm medulla derived from neural crest (is neural tissue) |
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what are the 3 zones of the cortex? what does each produce? |
zona glomerulosa: aldosterone-- responsive to angiotensin 2 zona fasciculata: cortisol, androgen-- responsive to ACTH zona reticularis: cortisol, androgen-- responsive to ACTH |
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what is medulla composed of? what does it secrete? |
composed of post-ganglionic sympathetic cells= chromaffin cells secrete catecholamines into blood |
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what diseases affect the adrenal cortex? the medulla? |
cortex: hyperplasia, atrophy, neoplasms, autoimmune, infections, hemorrhage
medulla: neoplasms |
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what is primary chornic adrenal insufficiency called?
what about inc aldosterone? inc cortisol? inc androgen? |
addison-- chronic adrenal insufficiency
inc aldosterone: conn syndrome inc cortisol: cushings inc androgen: congenital adrenal hyperplasia |
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what causes primary hyperplasia? secondary? what is most common? what causes secondary hyperaldosteronism and hypercortisolism? |
primary: congenital lack of synthetic enzyme secondary: inc trophic factor (ACTH, renin/angiotensin)
hyperaldo: hyperplasia of zona glomerulosa bc of inc renin/angiotensin
hypercortisol: hyperplasia zona fasciulata/reticularis due to inc ACTH |
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what is congenital adrenal hyperplasia? |
adrenogenital syndrome lack of a steroid hormone synthetic enzyme cant produce cortisol/aldosterone so it gets pushed into androgen pathway (you get virilization and salt wasting) |
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what causes adrenal cortical atrophy? |
prolongd medicinal glucocorticoids (dec ACTH) leads to bilateral adrenal cortical atrophy
if therapy abruptly withdrawn, atrophic adrenals cannot secrete adeuqate enough hormones so you get secondary adrenal insufficiency |
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is adenoma of adrenal cortex common? |
no gross-- single, solid, encapsulated, yellow histo: pale, lipid laden, well differentiated cells
can be functional or non function if too much cortisol-- cushing syndrome too much aldo: conn syndrome |
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is carcinoma of the adrenal cortex common? are theyfunctional? |
no when functional, remaining adrenals are atrophic (inc cortisol, dec ACTH secretion by ant. pituitary--> adrenal cortical atrophy) 80% are functional-- when functional, its cushing syndrome |
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adrenal mets come from which 3 places? what is it called if mets destroy >90% of adrenal tissue? |
lung, breasts, melanoma path: glands enlarged, metastatic tissue present, malignant cells if destroys 90% tissue--> primary chronic adrenal insufficiency: addisons disesase |
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autoimmune adrenalitis |
anti-adrenal Ab can lead to atrophy early on: lymphoid infiltrates into cortex chronic: fibrosis of cortex, medulla is sapred
clinical: addisons disease (due to autoimmune destruction) |
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tuberculosis adrenalitis |
underveloped countries, worldwide is most common cause of primary chronic adrenal insufficiency
gland enlarges then atrophies, you see granulomas (macrophages and multinucleate giant cells)
if TB destroys adrenal gland--> addisons disease |
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adrenal hemorrhage 3 etiologies |
anti-coag therapy DIC bilateral hemorrhage->acute hemorrhagic necrosis bacterial sepsis: waterhouse-friderichsen syndrome: caused by neisseria meningiditis and then psueodomonas septicemia --> hypotension, DIC--> massive adrenal hemorrhage, skin purpura--> death |
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endocrine causes of adrenal problems |
dec trophic hormones lead to secondary adrenal insufficiency (dec CRH from hypothalamic destruction and dec ACTH from pituitary descturion
inc of each can lead to secondary adrenal hyperplasia (cushings) |
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define cushings |
excess cortisol from either: medicinal glucocorticoids pituitary corticotrope adenoma (inc ATCH) adrenal cortical hyperplasia, adneoma, carcinoma or ectopic ACTH |
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adrenal medulla which neoplasms are here? |
neuroblastoma and pheochromocytoma: chromaffin cells which secrete catecholamines-->hypertension rule of 10%- 10% bilateral, malignant, occur in children, extra-adrenal surgically correctable form of hypertension |
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where is aldosterone (and other mineralcorticoids) produced? targets? hormonal effects? stimulatory factors? |
zona glomerulosa kidneys, blood vessels, heart na/k regulation, BP regulation sitmulated by angiotensin 2, high K+, low Na+ |
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cortisol/glucocorticoids: where is it produced? targets? hormonal effects? stimulatory factors? |
zona fasciculata targets most cells protein, fat, carb metabolism ACTH is stimulatory factor |
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androgens (DHEA, androstenedione): where is it produced? targets? hormonal effects? stimulatory factors? |
zona reticularis targets most cells sexual maturation and bone/muscle growth ACTH stimulates it |
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where are catecholamines producd (DA, NE, EPI) targets? hormonal effects? stimulatory factors? |
medulla targets most cells cardiac stimulation, BP increase sympathetic fibers stimulate it |
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where does aldosterone work? |
increases gene transcrpition in principle cells of the renal collecting duct to reabsorb Na and excrete K |
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how does renin and angiotensin regulate aldosterone? |
renin stimulates alpha globulin -->angiotensin I --> angiotensin 2, which stimulates adrenal cortex (glomerulosa cells) to produce aldosterone, which leads to renal Na and water retention --> inc EC fluid volume |
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which factors inhibit aldosterone secretion? activate it? |
inhibited by increasesd EC fluid volume and arterial pressure activated by dec EC fluid volume and dec arterial pressure and Na+ depletion |
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what 5 things does cortisol effect? BBIIG? |
inc blood pressure dec bone formation dec inflammation dec immune function inc gluconeogenesis (and lipoplysis/proteolysis)
it is a stress hormone that mobilizes stores for immediate use |
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what does ACTH stimulate to produce cortisol? |
stimulates uptake of lipoproteins in fasciculata cells and conversion of cholesterol to pregnenolone (rate limiting step in production of cortisol) |
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what are function of androgens? |
female: promote dvlpmnt of pubic and axillary hair contribute to libido males: (less signif after puberty), but testosterone from testicles is major androgen) |
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steps of catecholamine synthesis |
tyrosine -> L-DOPA-> DA-> NE-> Epinephrine
homovanillic acid is breakdown product of DA VMA, normetanephrine is bkdwn product of NE metanephrine is bkdwn product of epinephrine |
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DA: target receptor, action, physio response NE EPI |
DA: D1, vasodilation in heart/kidney/mesentary inc PVR, pulse pressure, MAP NE: alpha, beta 1, intense vasoconstriciton EPI: alpha, beta 2: vasodilation in skeletal muscle, vasoconstriction in skin/viscera, stimulation of cardiac muscle cells physi: neutral on PVR, CO, HR
metab effects: fight or flight-- inc glycogenolysis/lipolysis, dec insulin release |
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what labs do you order for adrenal cortex testing? |
aldosterone (plasma, in conjunction w/ renin) cortisol (plasma or 24 hrs urine) androgens (DHEA, androstenedione, testosterone, speicifc steroids, DNA studies |
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what labs do you order for adrenal medulla testing?
what factors affect catecholamine measurement? |
catecholamines (plasma or 24 hr urine) metanephrines (plasma or 24hr urine)
stress, anxiety, exciemtent, drugs (many!), withdrawal states-- test under calm, controlled coniditions with discontinued interfering meds if possible |
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what factors will inc aldosterone? what factors will dec aldosterone? |
low na diet, volume depletion/diuretics, upright posture will increase aldo
high na diet, volume overload/saline infusion, supine posture will dec aldo |
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which factors affect cortisol measurement? |
cortisol is 90% bound to cortisol binding protein factors that inc CBG (estrogen containing OCPs) will increase total measured cortisol, factors that dec CBG (severe liver dysfunction) will dec total measured cortisol
neither should affect urinary or salivary free cortisol
cortisol is secreted in cricadian pattern-- highest in AM before waking, lowest at night |
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clincal features of adrenal insufficiency:
cortisol deficiency: (6) aldosterone def: (5) aldrenal androgen deficiency (1) |
cortisol: fatigue, anorexia/weight loss, hypoglycemia, hyponatremia (dilutional), poor tolerance of stress-vascular collapse-- these can all be primary or 2ndary hyperpigmentation (primary only)
aldo: hypvolemia, postural hypotension, hyperkalemia, hyponatremia (salt loss), metabolic acidosis androgen: loss of pubic and axillary hair these are only seen in primary AI |
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labs for primary AI causes? |
labs: low cortisol, low aldosterone, high renin and angiotensin, high ACTH and CRH
causes: idiopathic (autoimmune), iatrogenic, infxn (TB, histoplasmosis, HIV), infiltrative disease (mets, amyloidosis), hemorrhage, inherited (congenital hpyerplasia, adrenal leukodystrophy) |
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secondary AI: labs, causes |
labs: low cortisol, normal aldo, renin, angiotensin, low CRH, low ACTH you wont have hyperkalemia bc you are able to get aldo from another source than ACTH
cause: pituitary/hypo tumor (adenoma, craniopharyngioma) iatrogenic (surgery, x ray, chronic high dose corticosteroid therapy) pituitary infarction (sheehans) infxn, granulomatous dz, idiopathic |
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what is rapid ACTH test? what does it tell you? |
large dose of synthetic ACTH (cosyntropin) is given in morning (when cortisol is highest), you see if cortisol responds yes: secondary no: primary |
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steps in evaluating adrenal insufficiency |
1. baseline plasma cortisol and ACTH 2. admin cosyntropin, draw plasma cortisol at 30 and 60 min-- if peak >20, normal, if <20, move on 3. baseline ACTH <20: secondary insufficiency baseline ACTH >200: primary insufficiency |
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2 form so congenital adrenal hyperplasia: what deficiencies, what are the defects? |
21-OHase (other one is 11hydroxylase) so progesterone cannot be convertedinto deoxycorticosterone or deoxycortisol you have mineralcorticoid deficiency and HYPOtension, cortisol deficiency, and increased weak adrenal androgens
cortisol def: severe: vascular collpase, vomiting, death in infancy partial: variable lack of tolerance due to stress
aldo def: sever: polyuria, volume depletion, hyperkalemia in infancy partial: compensated with adequate salt intake
adrenal androgen excess: sever: masculinization of external genitalia in female infants, ioxsexual precocity in boys partial: hrsutism (male patterned hair growth) and irregular menses in women |
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whih step in the pathway is stimulated by ACTH? if there is an ACTH deficiency, what will be affected? |
step from cholesterol to pregnenolone |
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pathophys of 11-hydoxylase deficiency |
cant go from 11-deoxycorticosterone to corticosterone or 11 doexycortisol to cortisol you get increased mineralcorticoids (excess 11-deoxycorticosterone) which causes HYPERtension you get symptoms of cortisol deficiency you get increased weak adrenal androgens |
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which steroids mainly affect mineralocorticoids? which steroids mainly affect glucocorticoids? |
mineral (aldo): fludrocortisone
gluco (cortisol): in lecture: hydrocortisone or prednisone also dexamethasone, also methylprednisolone and prednisolone, prednisone need increased doseing during stress
usually dont need to replace mineralcorticoid during secondary adrenal insufficiency except in conditions of volume depletion |
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clinical features of cushings syndrome |
glucocorticoid excess (hypercortisolism) muscle wasting, weakness easy bruising, poor wound healing, osteoporosis, fractures central obseity glucose intolerance psych disturbance
mineralocorticoid excess: salt retention, HTN, edema, hypokalemia, metabolic alkalosis
androgen excess: excess hair, acne, amenorrhea |
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lab values for cushings due to adrenal tumor due to ACTH producing pituitary tumor?
what happens to each after low dose dexamethasone and high dose dexamethasone? |
adrenal tumor: high cortisol, low ACTH , low CRH (will not suppress to dexamethasone)
pitutiary tumor- cushings: low CRH, high ACTH, high cortisol, WILL suppress to high dose dexamethasone (so eventually responds to feedback, but set point is higher)
ectopic ACTH producing tumor: low CRH, high ACTH, high cortisol (will not suppress to dexamethasone)
all will have high urine cortisol |
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steps in evaluating cushings: |
1. 24 urine free cortisol, lose dose dexamethasone suppression test (if normal its not cushings) 2. plasma ACTH, high dose dexameth suppression --> if ACTH undetectable, no suppression-- adrenal tumor --> if ACTH elevated, no suppression-- ectopic ACTH syndrome --> if ACTH normal or evelated, suppression to (50% baseline--> cushings disease (pituitary)
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what are management options for cushings? |
ACTH secreting pituitary tumor: remove it though transphenoidal approach, bilateral adrenalectomy if you cant remove: blockers of ACTH secretion by tumor or steroid biosynthesis
primary adrenal tumor: surgical resection-- sucessful for adenomas, not carcinomas carcinoma: block steroid biosynthesis, adrenolytic drugs
ectopic ACTH syndrome remove/ablate primary tumor with surgery, radiation block therapy: block steroid biosynthesis bilateral adrenalectomy |
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what is drug action of cabergoline and pasireotide? drug action of mifepristone? spironlactone?
ketoconazole? aminoglutethimide? |
decreased ACTH secretion by tumor
mifepristone: blocks glucocorticoid receptor spironolactone: blocks mineralcorticoid receptor
ketoconazole and aminoglutethimide: inhibit steroidogenesis |
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what are endocrine causes of hypertension? |
1. primary essential HTN 2. renin-angiotensin mediated (coarctation of aorta, renin-secreting tumor, renovascular) 3. mineralocorticoid mediated- primary aldosteronism, cushings, CAH, exogenous glucocorticoids, mineralocortioids
4. volume mediated: acromegaly
5. catecholamine mediated; pheochromocytoma, neuroblastoma, acute stress
unkonwn mechanisms: hypercalcemia
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causes of mineralocortoicoid excess |
primary hyperaldosteronism: aldo producing adenoma, idiopathic hyperaldosteronism
secondary hyperaldosteronism: renal artery stenosis, diuretic use, renin producing tumor
"apparent mineralocorticoid excess"-- clinical features mimic this |
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what are features of primary hyperaldosteronism? |
sodium retention with plasma volume expansion hypokalemia due to excessive potassium excretion (remember that in order to reabsorb water you need to reabsorb Na so you lose K) |
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what steps do you do to screen for hyperaldosteronism when you have hypertension and hypokalemia? |
plasma renin activity and plasma aldosterone concentration
both elevated: secondary hyperaldo (diuretic use, renovascular HTN, renin secreting tumor, coarctation of aorta)
if PRA low, PAC high-- primary aldosteronism congenital adrenal hyperplasia, cushings
investigate for non aldosterone mediated causes |
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what are confirmatory tests for hyperaldosteronism? |
failure of renin (and aldo) to suppress in response to volume expansion by saline infusion
failure of renin and aldo to increase in response to volume depletion (lasix)
also you can look at see if it changes in posture: you SHOULD see inc in aldo when you stand up |
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how can you tell a difference between aldo producing adenoma and idiopathic hyperaldosteronism? |
APA: aldo does not increase with standing IHA: aldo may increase with standing
can help to distinguish etiology of primary hyperaldosteronism |
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once you have confirmed primary aldosteronism, whats next? |
localizing tests: adrenal CT scan if you have normal microndolatriyt, bilateral masses, its probably not APA screen for GRA?
if its high prob APA: do adrenal venous sampling (if you find that its an adenoma: do unilerateral adrenalectomy LOOK AT FLOW CHART |
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what is common cause of secondary hyperaldo? |
renal artery stenosis |
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what are 4 drug classes that block RAAS? |
renin inhibitors ACE inhibitors (enzyme that catalyzes Ang 1--> Ang 2) angiotensin 2 blockers aldo receptor antagonists |
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what is eplerenone? |
mineralcorticoid receptor antagonist |
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pheochromocytoma |
rare tumor that can cause catecholamine excess, diff to diagnose symptoms during paryxysms headache, sweating, forceful heartbeat, anxiety, tremor, fatigue, N/V
symtpoms between paroxysms: inc sweating, cold hands and feet, weight loss, constipation, POSTURAL HYPOTENSION
tumor characteristics: 10% of benign tumors are bilateral, 10% originate in sympathetic ganglia outside renal medulla, 10% are malignant
LOOK AT FLOW CHART preferred tx is surgical removal, medical tx is combo of alpha blockers then beta blockers given preoperatively |
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if you suspect unilateral adrenal mass, what do you do? |
in young person with clear mass and biochemically proven primary hyperaldosteronism-- do surgery (adrenalectomy) in all others, adrenal vein sampling is recommended- helps to determine is aldo excess is unilteral |
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what is tx of choice for aldo producing adneoma (conns syndrome)? |
surgery but if not, mineralcorticoid blockign drugs should be used: spironolactone (also blocks androgen and progesterone receptors) eplerenone: expensive but more specific potassium supplementation may be required |
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what history suggests renal arterial stenosis? |
worsening HTN with evidence of atherosclerosis or an abdominal bruit you would confirm with renal arteriogram (would demonstrate high gradient of plasma renin activity from venous drainage of ischemic kidney compared to peripheral circulation), renal ultrasound, MRI |
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what is tx for renal arterial stenosis? |
surgery or baloon angioplasty to open stenosed renal artery HTN can be controlled with drugs (ace inhibitors, ARBs, direct renin inhibitors) |
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which lab value is most specific for pheochromocytoma?
which one is most sensitive? |
specific: elevation of 24 hour urine metanephrines sensitive: elevation of plasma metanephrines (but they can be falsely elevated in stressed or sick patients)
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what is phenoxybenzamine? |
non selective alpha blocker used before surgery also propanolol to be used before pheochromocytoma surgery too |
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what is screening test for hyperaldosteronism? confirmatory test? |
screening: serum aldosterone: plasma renin ratio confirm: aldosterone after salt loading or saline admin |
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how do you treat primary renal insufficiency? |
hydrocortisone and fludrocortisone |
