endocrine- adrenal Flashcards
where are the adrenal glands located? what are the two parts to them?
Retroperitoneal, superior pole of each kidney
2 separate glands-cortex & medulla
cortex of adrenal gland - essential? what does it secrete? # of zones?
Outer cortex-mesoderm
Essential for life (only source of cortisol)
Secretes steroid hormones
3 zones
medulla of adrenal gland - essential? what does it secrete?
Inner medulla-ectoderm
Secretes catecholamines
not essential for life
what are the 3 zones of the outer adrenal cortex? which is the thickest?
- outer: zona glomerulosa
- middle: Zona fasciculata -thickest
- Zona reticularis
what are each of the 3 zones of the outer adrenal cortex made of?
“Salt, sugar, & sex…the deeper you go, the sweeter it gets”
Zona glomerulosa- Mineralocorticoids: Aldosterone
Zona fasciculata- Glucocorticoids: Cortisol
Zona reticularis - Glucocorticoids: androgens
(think “GFR” - as its right about kindey)
which adrenal cortex zone responds to ACTH? which doesnt?
zona glomerulosa - not affected
zona fasisculata- responds to ACTH
adrenocortical steroids are all dervied from _____.
cholesterol
Glucocorticoids & mineralocorticoids have \_\_\_ carbons Androgens have\_\_\_carbons (kinda weeds)
21
19
cholesterol –> glucocorticoid: changes to molecular structure? what about for glucocorticoid –> cortisol?
Glucocorticoids require C11 & C21 hydroxylation
Cortisol requires C17 hydroxylation as well
cholesterol –> aldosterone: changes to molecular structure?
Aldosterone requires C11 hydroxylation & has C18 double bond
cholesterol –> androgens: changes to molecular structure?
Androgens lack C20-21 side chain & have C17 double bond (ketone group)
adrenal cortical steroid synthesis: zone contain enzymes specific to hormones produced… ZG has _____, ZR has _____
ZG has aldosterone synthase
ZR has 17, 20-lyase
the rate limiting step in adrenal cortical steroid synthesis: ______ stimulates initial conversion of cholesterol to ______?
ACTH stimulates conversion cholesterol –> pregnenolone
what are the precursor molecules that can sub for our key adrenal hormones?
Corticosterone has glucocorticoid activity (can sub for cortisol)
Corticosterone & 11-deoxycorticosterone have mineralocorticoid activity (can do what aldosterone does but not as well - can sub for it)
* from pathway: deoxy –> corticosterone –> aldosterone
when are the highest levels of adrenal hormones ? (time of day)
Highest levels between 4am-8am
what causes the secretion of adrenal corticosteroid? what is it affected by?
Results from pulsatile secretion of hypothalamic CRH
Affected by sleep-wake cycles & sensory input
cortisol’s effect on the HPA axis?
inhibits it
- comes out adrenal cortex- inhibits both ant. pituitary (release of ACTH) and hypothalamus (release of CRH)
6 functions of cortisol
- Promotes gluconeogenesis
- Decreases peripheral glucose utilization (diabetogenic)
- Potent anti-inflammatory effects
- Inhibits immune response
- Upregulates α1 receptors on vascular smooth muscle (too much cortisol = HTN)
- Increases GFR
why is cortisol necessary for survival?
needed for times of metabolic stress (like a broken bone)
–> hyperglycemia –> more glucose available to brain.
what two things does aldosterone increase?
- Increases Na+ reabsorption
- Water follows
- Increases ECF volume - Increases K+ (or H+) secretion
what do androgens do?
Promote masculinization
what is addison’s disease?
chronic hypoadrenocorticism: Insufficient glucocorticoid (cortisol) (& usually mineralocorticoid - androgen) production
most common cause of addison’s (chronic hypoadrenocorticocism)?
Iatrogenic:
Rapid withdrawal of glucocorticoids, post-adrenalectomy, ketoconazole/fluconazole.
(adrenal gland goes on strike when we give steroids, if you take them off fast- we didnt give it enough time for gland to recover)
most common cause of non-iatrogenic hypoadrenocorticocism? (kinda weeds)
Autoimmune adrenalitis -auto antibodies against adrenal cortex
(comes with hashimoto’s (thyroiditis that causes hypothyroid): treating without covering with steroids- known as Schmidts syndrome)
3 other causes of hypoadrenocorticocism? (addisons)
- Corticosteroid insufficiency of critical illness: ICU patients
- Infections
- Secondary (ACTH deficiency)
5 S+S and hypo adrenocorticisim (kinda weeds) (addisons)
- Weakness
- Weight loss
- low BP (hypotension)
- Often labeled as being “mental”
- Sudden unexpected death :from common cold, flu, etc.
* none specific enough to raise suspicion
4 substance level changes in hypoadrenocorticism (kinda weeds)
metabolic acidosis Hypoglycemia Hyperkalemia Hyperpigmentation (high ACTH)-check nipples, palmar creases, old scars *none specific enough to raise suspicion
what is acute hypoadrenocorticism known as? what does it cause?
adrenal apoplexy/ Addisonian crisis (unexplained deaths from relatively minor infections/illness)
“Sudden onset “warm” shock, accompanies stress, often fatal.”
what are the two causes of acute hypoadrenocorticism (adrenal apoplexy/ addisonian crisis)
- Undiagnosed adrenal insufficiency
2. Known Addison’s without supplemental steroids
what is Waterhouse-Friderichsen syndrome?
type of hypoadrenocorticism:
- Massive intra-adrenal hemorrhage in setting of sepsis (usual meningococcal, but not always.. still suspect acute addisons)
- Shock, death within hours
txt for waterhouse-friderishsen?
Give the steroids without waiting for the labs to come back.
treatment for hypoadrenocorticism: primary addisons
- glucocorticoid & mineralocorticoid: (Hydrocortisone/fludrocortisone)
- Maintenance & stress doses
- when you anticipate someone will be under metabolic stress- bump up to dose to cover metabolic stress
treatment for hypoadrenocorticism: acute adrenal insufficiency (3)
- Salt, sugar, steroid replacement
- Support organ function
- Search for underlying cause
what is cushing’s syndrome? who gets it?
hyperadrenocorticism - excessive glucocorticoid production
-most common in women
2 keys to signs of hyperadrenocorticism
- Excess fat deposits in the body*
- Diagnosis is partially a lack of circadian rhythm when cortisol is secreted
S+S of hyperadrenocorticisim
Weight gain Truncal obesity/moon face Thin skin, striae, poor healing Hirsutism Hypertension Glucose intolerance Osteoporosis Amenorrhea Often labeled as being “mental”
Dx test for hyperadrenocorticism
24 hour urinary free cortisol test: 800/2000 cortisol levels = NORMAL (high cortisol 8am, low 8pm = normal) -reversal of these levels = pos. Dx **document hypersecretion of cortisol & loss of circadian rhythm
how do you distinguish cushing’s disease vs syndrome?
low (syndrome) vs high (disease) dose dexamethasone suppression test
txt of hyperadrenocorticism is usually based on cause, often involve surgery, but what are two drugs that can be used? (kinda weeds)
Metyrapone & ketoconazole inhibit steroid synthesis
primary hyperaldosteronism: what is it and what causes it?
Overproduction of mineralocorticoid (causes water and sodium reabs)
Due to adrenal hyperplasia or adrenal adenoma (Conn’s syndrome)
surgery-correctable cause of hypertension? (0.5%)
primary hyperaldosteronism
S+S of hyperaldosteronism
Hypertension Hypokalemia Metabolic alkalosis Low renin levels No edema
primary hyperaldosteronism-caused HTN: with thiazide diuretics can cause what?
fatal hypokalemia!
Dx of primary hyperaldosteronism
Diagnosis via high aldosterone-to-renin activity ratio
- if renin is low and aldosterone is high, then aldosterone level is inappropriate
removal of adrenal adenoma (cause of hyperald.): what should you be sure to do?
theyre often small..
Renal vein sampling can determine laterality (which side the adenoma is on so you know which side to remove*)
txt of adrenal hyperplasia (cause of hyperald.)
Spironolactone (K sparing*)
what is congenital adrenal hyperplasia (CAH) ?
a group of autosomal recessive disorders
- deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both
- Lack of negative feedback from cortisol on ant pituitary causes increased ACTH (to try to stimulate adrenal glands) = adrenal hyperplasia
- Because of the blocks, most of the precursors go down the androgen pathway*
adrenogenital syndrome: two types? which is most common ?
a type of CAH
- many types: two main types we care about
21- hydroxylase deficieny (MOST COMMON)
11-β-hydroxylase deficiency
adrenogenital syndrome: 21-hydroxylase deficiency vs 11- beta hydroxylase (maybe weeds)
21-hydroxylase deficiency No cortisol, aldosterone, or DOC Severe deficit: Salt-wasting, dehydration, death in severe forms MORE LIFE THREATENING 11-β-hydroxylase deficiency Huge amounts DOC produced Don’t get much cortisol produced* Hypertension, salt-retention
what do you want to Consider in females with amenorrhea or moustaches?
adrenogenital syndrome (kind of CAH)
- 21-hydroxylase deficiency most common
Dx: Serum 17-OH-progesterone
If normal-ish, provoke with ACTH stimulation
Dx adrenogenital syndrome
Stimulation test:
1. Administer ACTH
2. Measure 17-OH-progesterone in 1 hour
Even mild elevations suggest disease
txt adrenogenital syndrome
Treat with glucocorticoid ± mineralocorticoid replacement (depends on the block type*)
Reconstructive surgery in severely affected female infants
what are most adrenal masses like?
about 75% are adenomas
- most can be left alone
what is the purpose of the adrenal medulla?
Not essential for life
produces catecholamines:
Source of adrenalin (epinephrine) & norepinephrine
what are the two disorders of the adrenal medulla?
both usually functional - secrete catecholamines 1. Pheochromocytoma: Adults Well-differentiated 2. Neuroblastoma: Children Poorly-differentiated
“paroxysms of extreme hypertension (230s/150 ex), headache, sweating, other autonomic disturbances”- what is this a classic presentation of?
pheochromocytoma
- result from compression/ischemia of tumor = secrete more Epinephrine
- more commonly produce sustained HTN
what % of pheochromocytoma are familial? who has to be screened?
30%
- family members need to be screened if someone has MEN IIa or IIb (RET oncogone) or von Recklinghausen’s neurofibromatosis (NF-1 mutation)
Dx of pheochromocytoma
24 hr urinary vanillylmandelic acid (VMA)
Plasma free metanephrines (can test this in urine too*)
txt of pheochromocytoma
- Surgical resection- subtle movement of the tumor can cause sudden BP drop**
- Careful fluid & BP management
Multiple endocrine neoplasia disorders (MENs) - what type hereditary nature?
Autosomal dominant disorders
-Predispose people to endocrine tumors
MEN I
“PPP”, “Wermer’s syndrome”
Chromosome 11, gene MENI, protein menin, tumor suppressor gene
1. Parathyroid hyperplasia/adenoma(s) (95%)
2. Pituitary adenoma
3. Pancreatic endocrine tumors (usually gastrinoma)
MEN IIa
“PPM”, “Sipple’s syndrome” Chromosome 10, gene RET, protein tyrosine kinase, proto-oncogene 1. Medullary thyroid cancer (100%) 2. Parathyroid adenoma(s) 3. Pheochromocytoma
which MEN do people get prophylactic thyroidectomy for?
MEN IIa and MEN IIb
MEN IIb
“PMM”, “Wagenmann-Froboese syndrome”
Chromosome 10, gene RET, protein tyrosine kinase, proto-oncogene
1. Mucosal neuromas (100%), also Marfanoid body habitus
2. Medullary Thyroid cancer (85%)
3. Pheochromocytoma
consequences of Dx a adrenal disease that is NOT actually there?
-lifelong medication, unnecessary surgery or radiation
consequences of failure to Dx adrenal disease?
death from disease that maybe had an excellent prognosis
general guidelines for adrenal testing?
- Single tests seldom establish adrenal disease
- Often utilize “stimulation” or “suppression” tests
- Get consultation with endocrinologist in equivocal cases or when screening is positive
Thin, tired patient with no appetite: what should you do? (3 steps to Dx and treatment)
maybe addisons
1. Screening-early morning (between 4 and 8am) serum cortisol
2. if <13 mg /dL –> get rapid ACTH stimulation test
(give 250 mcg synthetic ACTH IV)
3. check Serum cortisol in 30-60 min
if > 18 mcg/dL = NORMAL
if < 18 mcg/dL =primary or secondary Addison’s
Consider giving dexamethasone pre-test to prevent crisis
Depressed, overweight patient with hypertension & hyperglycemia
maybe cushings- check cortisol levels (3 possible ways)
1. serum cortisol: 8pm levels over 1/2 of 8am levels (higher at night) = Dx
2. 24 hr urine free cortisol: >108 mcg/dL (high) =Dx
3. low dose dexamethasone suppression test: give at midnight and measure cortisol in morning.
lack of suppression = Dx
4. late night salivary cortisol
when might someone get falsely high positive cortisol tests? (giving false impression of cushings)
False-positives in severe depression, hard drinkers, pregnancy
two tests to distinguish cushings Dz from others?
- high dose desamethasone suppression test: Pituitary adenomas are suppressed, adrenal tumors & ectopic sources of ACTH are not
- metyrapone stimulation test: Potent inhibitor of 11-β-hydroxylase (enzyme important for aldosterone + cortisol production)
- normal response: decr. cortisol, compensatory increase ACTH and 11-deoxycortisol
- -> Pituitary adenomas (cushings) stimulated
- -> adrenal tumors are not:
- -> ectopic ACTH sources maybe?
Hypertensive patient with hypokalemia off meds
hyperaldosteronism: renin-independent increase in aldosterone
Dx: serum aldosterone-renin activity ratio
> 920: primary aldosteronism
< 28 : Addisons
Nervous patient with hypertension & headaches: what do you think? 3 possible ways to Dx?
pheochromocytoma
- 24 hr urinary vanylmandelic acid (VMA) & metanephrines
- Plasma free metanephrines
- I131 metaiodobenzylguanidine isotope scan
low vs high serum ACTH suggest what?
Low indicates adrenal tumor Cushing’s syndrome
High indicates ectopic ACTH Cushing’s syndrome
Corticotrophin-releasing factor stimulation test
pituitary adenomas respond, others dont
low dose vs high dose dexamethasone tests results
Low-dose dex suppressions rule in/out Cushingism
High-dose dex suppressions attempt to differentiate Cushing’s disease from other causes
