Adrenal Gland (Path B5)

Myelolipoma remember, these occur on the adrenal gland and are made up of fat tissue AND myeloid tissue; they are benign!

-benign neoplasm -maturae adipsoe tissue -incidental findings -adrenal tumor

CYP11B1

11-hydroxylase deficiencyh is due to deficienycin?

aldactone or spironolactone bodies due to tx w/ spironolactone (Cf. sk) will be seen in also in aldosterone producing adreanal cortical adenoma

Adrenal gland. What are these?

the most common form of *Cushing's Syndrome* is from *Exogenous source of glucocorticoids* -suppresses ACTH ->low ACTH so NO hyperpigmentation -*osteoporosis* -gluconeogenesis -> *hyperglycemia* & *IR* -> can cause *DM* -suppresses *GnRH* -> suppresses LH & FSH -> abnormal menstral cycle in females -moon facies & HTN b/c glucocorticoids have intrinsic aldosterone effects -> fluid & water retention -> HTN -glucocorticoids ALSO increase the sensitivity to Epi and Ne on vascular system -> increase vasoconstriciton & thereofre HTN -also will lead to more demargination of Neu & poor wound healing, labile/depression/anxiety (psych effects) -central obesity & stria (b/c of catabolic effects on collagent & rupture of blood vessels) -catabolic effects on muscle -> atrophy of proximal muscles and weakness can also get glucocorticoids from other sources such as *adenomas* *cortisol secreting adrenal tumor* -releases cortisol -DEPRESSES ACTH level (negative feedback) -> atrophy of BOTH adrenal galnds (contralateral full; ipsilateral NON tumor is atrophic, too) (*particularly the zona fasiculata*) *ACTH secreting pitutiary Adenoma* -secretes ACTH -> (pomc -> MSH & ACTH) ->*hyperpigmentation* -hyperpigmentation is in sun exposed areas & healed wounds *ectopic ACTH tumor* -most often in lung -? bronchial carcinoid tumor or small cell tumor -produces ACTH and therefore Hyperpigmentation *diagnosing* -PM salivary cortisol level -24 hour urinary cortisol level -Dexamethasone -> low dose in ACTH Adenoma of adrenal gland NO change but HIGH dose DXM DOES lower it -for ecotpic ACTH secreting CA (carcinoid or small cell lung CA) -> will NOT affect ACTH at all or cortisol TX: -mifeprostone -mitostane -ketoconazole -spirinolactone for HTN -metyrapone surgery can tx -also if bilateral removal of adrenal glands -> *nelson syndrome* -> MASSIVE increase in ACTH & increase in side of adenoma -> can push on sella turcica, HA, vision changes, hyperpigmentation

Cushing's Syndrome

outer to inner Dark ZG light ZF innter ZR

Layers of adrenal gland

-*zona glomerulosa forms aldosterone* and *mineralocorticoids* -anterior pituitary produces *ACTH* which activates *desmolase* which does *cholesterol -> pregnenolone* -pregnenalone becomes *progesterone* -next *progesterone* is acted on by *21-hydroxylase* and becomes *11-deoxycorticosterone* -11-deoxycorticosterone is acted on by *11-hydroxylase and becomes corticosterone* -corticosterone is acted on by *18-hydroxylase* (which is *activated by AII*) and becomes *aldosterone

Discuss the formation of the major product made in the zona glomerulosa of the adrenal cortex

-the major product of the *zona fasiculata* is *cortisol* or *glucocorticoids* -pregnenolone is acted on by *17-hydroxylase* (pregnenalone was made in the zona glomerulosa) which forms *17-hydroxypregnenolone* -17-hydroxypregnenalone becomes *17-hydroxyprogesterone* -another way you can get *17-hydroxyprogesterone* is from *progesterone in the zona glomerulosa being acted on by 17-hydroxylase* which yields *17-hydroxyprogesterone* as well -17-hydroxyprogesterone is acted on by *21-hydroxylase* and produces *11-deoxycortisol* -11-deoxycortisol is acted on by *11-hydroxylase* and produces *cortisol*

Discuss the formation of the major products in the zona fasiculate of the adrenal cortex

-major products of the adrenal cortex *zona reticularis* is *testosterone* (aka androgens) -*17-hydroxypregneolone* is acted on by *17-hydroxylase* and forms *DHEA* (dehydroepandrosterone) -*DHEA* will become *androstenedione* (both of which are aka *17-ketosteroids* -you also can get *androstendione* by *17-hydroxyprohgesterone being acted on by 17-hydroxylase* -androstendione beomces *testosterone*

Discuss the major products and formation of them in the zona reticularis of the adrenal cortex

ishcmich infarct of pituitary grand folliwng post partum bleeding pregnancy induced pitutary growth -> increase susceptibility tohypoperfusion. usually presents w/ failure to lacta, absent mentstration and cold intollerance

** Sheehan's syndrome? *watch picmonic and then make note card and then edit this one :) *

-adrenal medulla tumor -> most common one in adults -> derived from *NCCs* -presympaptic gangionic synapse on adrenal medulla -10-10-10 rule: 10% are malignant; 10% are bilateral;10% ocrru outside of the adrenal medulla -familial are more likely to be bilateral assocaited contions: -*VHL* -> hemangioblastomas, bilateral clear cell renal CA, AD -*MEN2* -> AD -*NF-1* -> AD, cafe au lait, neurofibromas all over body *pheos produces -> NE, Epi & DA* can occurs *outside of the adrenal medulla* -> along sympathetic ganglia -> *along spinal column* symptoms: -HA -*episodic* -tachycardia -*HTN* usually most pronounced -sweating & anxiety tx: -surgery -*frist* give phenoxybenzien (alpha non selective blocker) -> *beta blockers SECOND* if give just beta blockers first -> SUPER high HTN which ain't good on gross: well demarcated tumor, yellow-ish; nests of cells w/ granule sin them (From hormones); dx w/ serum and urine -> look for metanephrines

Pheochromocytoma

-due to pituitary gland issue -> low ACTH therefore low MSH (no hyperpigmentation) -> low Cortisol -often assocaited w/ othr pituitary hormone derrangments -*aldosterone is normal and is not affected* -> controled by RAAS

Secondary Adrenal Insufficiency

-often associated w/ long term use of glucocorticoid pharm. drugs -*low CRH -> Low ACTH -> low cortisol* -aldosterone level NOT affected -> maintained and controled by RAAS -nothing hittinag the adrenals -> they *atrophy* -do NOT stop glucocorticoid therapy suddenly w/ thes patients -> tapper off to allow the adrenal glands to gain their normal funciton

Tertiary Adrenal Insufficiency

-12 yrs of age onset -hypoparathyroidism and mucocutaneous candidiasis -AR

Type I Polyglandular Adrenal Insufficiency

Mean onset at 24 years of age Autoimmune thyroiditis & type 1 diabetes mellitus Autosomal dominant

Type II Polyglandural Adrenal Insuffieicney

aldactone bodies

adrenal ctx. what are these?

Primary Pigmented Nodular ADrenal Disease (PPNAD) -> this one is micronodular

adrenal galnd dx?

in ZG -> aldosterone -> conn syndrome

adrenal gland adenoma. What s this likelyh producing?

ZF -> glucocroticoids

adrenal gland zone

adrenal galnd adenoma (remember sk what it can due) -> low ACTH -> cushing syndrome

adrenal gland; what i this?

adrenal medulla

adrenal layer

-dense core grnaulaes in pheochromocytoma

adrenal medualla dx

Conn's Syndrome

another name of rpimrary hyperaldosteronism

left is normal; right shows hyperplasia of ZF -> due to pituitary adenoma producing ACTH usually (ACTH depednent)

cf. left vs. right adrenal glands

top -> normal bottom -> hyperplastic (mainly ZF) -> ACTH excess! usually pituitary adenomoa/liesion producing tones of ACTH cf. sk

discuss the top vs. bottom adrenal glands. What caused the bottom one to what it has done?

nodular adrenal cortical hyperplasia -> primary aldosteronism

dx?

ZR -> sex storieds

layer of adrenal

Congenital Adrenal Hyperplasia with 21-hydroxylase deficiency

most common CAH

Biltaeral Adrenal Hyperplasia (idopathic!)

most common cause of Conn's Syndrome?

lung tumors -> small cell lung CA & bronchial carcinoid

most common ectopic ACTH paraneoplastic syndrome?

ZG

name zone of adrenal

see picutre

review RAAS!

cf. sk and review!

review dx of primmary aldosteronism (not super high yield)

Adrenal hemorrhage in Waterhouse-Friederichsen syndrome

this is an adrenal gland. Dx?

hyperaldosteronism -most common cause is *bilateral idiopathic hyperaldosteronism* -unsure of the pathophys and BOTH adreanl gland zona glomerulosas will be hyperplastic -second most common cuase is *adrenal adenoma that secretes aldosterone* -well circumscribe, yellowish gross look w/ aldosterone secretion; contral-lateral adrenal galdn will be *normal size* b/c Aldosterone will not negatively feed back on hte HPI axis (ACTH is what controls the size of the adrenal glands) -adenoma's will also have *spirinolactone bodies* -sx: -HTN (due ot Na and water retention) -Hypokalemia (aldo -> Na/K pumps in collecting ducts->K secretion) -Low renin (b/c of wtaer retention -> inhbits RAAS [normally activated in HYPOVOLEMIC STATES]) -metabolic alkalosis -> aldosterone activating alpha-intercelated cells in the distal collecting ducts to secrete H+ will lead to *aldosterone escape* -tremendous fluid retention -> increased RBP -> increase GFR ->leads to diuresis and pressu renatruesis (loss of water and Na) -> high volum estate will stretch atria -> ANP released -> augments pressure naturesis - also can develop from ectopic or adrenal carcinoma secreting Aldosterone (which, though, is rare) dx of primary aldosteroneism -> *salt suppression test* -> eat salt for a few days -> should suppress aldosterone -> if aldosterone is high still -> they have primary aldosterone *secondary hyperaldosteroneism* -makred by *high Renin* which activates RAAS -renovascular HTN (from fibromuscular dysplasia or bilateral renal artery stenosis), hepatic cirrosis, tumor secreting renin (at JGA) and nephrotic syndrome and HF -> all lead to poor perfusion of kidneys -> activation of RAAS -> hyperaldosteronism secondary to something tx of hyperaldosteronism: surgery to remove adenoma or CA if you can, spirnolactone, low salt diet *hypercortisolism* -will cause *cushing's syndrome or dz* -glucose intolernace, central obesity, strai, skin atrophy, moon facies -can be from an *zona fasiculata adenoma that secrete cortisol* -> hypercortisolism -> *suppresses ACTHG -> contralateral adrenal gland AND contralateral sid eof the adrenal galdn that has adenoma become atrophic -can also be from tumor

Adrenocortical Hyperfunction: Hyperaldosteronism & Hypercortisolism (all)

*General characteristics of 21 & 11 hydroxylase deficiencies* -HIGH amounts of *ACTH* b/c of no negative feed back on anterior pituitoary -> leads to *hyperplasia of adrenal glands* -*hypderpigmentation* is seen as well (because MSH increases along with ACTH [POM-C is cleaved into ACTH and MSH]) -in *severe 21 or 11-hydroxylase deficiencies* females will have *amgiguous genitalia* at birth -in *milder* forms of 21 or 11-hydroxylase deficiencies females will have *spotting* or irregular menses -clitoromegaly & hirsitism & acne *21-Hydroxylase Deficiency* -makes lots of *androgs* (testosterone) b/c cannot make *aldosterone* (hypoaldosteronism) -*hyponatremia* (salt wasting) b/c of low aldo. -*hyperkalemia* b/c of low aldo -*Type IV RTA* -*high Renin (high RAAS) b/c of low aldo -> hypovolemia -> renin activation and release* -*hypotension* and potentially even *hypovolemic shock* b/c of such low amounts of aldosterone -accumulates *progesterone* and especially *17-hydroxyprogesterone* and of course *androgens!* *11-hydroxylase deficiency* -build up of *11-deoxycorticosterone & 11-deoxycortisol* and of course *androgens* (Testosterone) -*HTN* b/c of HIGH *hyperaldosteronism* b/c *11-deoxycorticosterone acts just like aldosterone (a minerocorticoid!)* -*low renin* b/c of high blood pressure and hyperaldosteronism (salt retaining) -*hypokalemia* b/c of *hyperaldosteronism* secreting all of the K+ at the collecting ducts/tubules! *17-hydroxylase deficiency* -poor development of gonads -boys -> *ambiguous genitalia at birth* b/c no testosterone to masculanize -girls -> *no secondary sex characteristics* (pubic hair, breast, etc.); *amennorhea* or late menarche -*hyperaldosteronism* so HTN, etc. b/c all of the reactions are stuck in the *zona glomerulosa* forming *aldosterone*

Congenital Adrenal Hyperplasia (CAH) all three big ones (1) 21-hydroxylase deficiency (2) 11-hydroxylase deficiency (3) 17-hydroxylase deficiency

*first some basics* the adrenal cortex review -zona glomerulosa -> mineralocorticoids (aldosterone) -zona fasiculata -> cortiosl (glucocorticoid) zona reituclaris -> andrens (testosterone) *Primary Adrenal Insufficiency* -marked by hypercoagulatble (thrombotic at adrenal veins) or *biltateral adrenal hemorrahge* -Waterhouse Fredrichsen Syndrome-> bilateral adrenal hemorrhage in the setting of sepsis (e.g., N. meningitidis) -hallmark is *hypocortisolism* which leads to -> *low vascular tone* -> Hypotension -> shock; as well as *low gluconeogenesis* -> *hypoglyecemia* -*ACTH is high* is primary adrenal insufficiency* -aldosterone is *low* -> *hyperkalemia* (no secretion in distal/collecting tubules/ducts); *hyponatremia* due to *volume loss* and high *ADH activation* as well as isotoninic water and Na loss, but still, hyponatremic due to massive amounts of ADH being produced *Chrinc Primary Adrenal Insufficiency aka Addison's Disease* -chronic, insidious onset usually (indolent) -women -> irregular menses, amenorhhea -orthostatic hypotension (poor cortisol regulation of vasdcualr tone) -usually is *antibody mediate* -> highly assocaited with *HLA-B8, DR3, DR4 Genes* -*POMC -> MSH (hyperpigmentaiton) & ACTH* - *Type 4 RTA seen,as well* *addison's dz also associated w/ disseminated TB* (most common cause worldwide)

Primary Adrenal Insufficiency