CM- Endo -3- Adrenal Disease lect 7-8
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| From what fetal origin is the adrenal cortex | mesodermal origin
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| During fetal development the adrenal cortex only has two zones what are they and what do they produce | fetal zone- produces mainly dehydroepiandrosterone (precursor for estrogen) this zone disappears after birth
Definitive Zone- synthesizes fetal cortisol and develops into the adrenal cortex after birth
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| Where are the adrenal glands typically found in the human adult | lies in the retroperitoneum above or medial to upper pole of the kidney
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| What surrounds the adrenal gland | fibrous capsule
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| Which part of the adrenal gland is larger the cortex or medulla | cortex- it accounts for 90% of gland weight
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| What are the arterial supplies for the adrenal gland | inferior phrenic artery, renal artery and the aorta
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| This part of the adrenal gland develops from primitve neural crest cells | adrenal medulla
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| Part of the adrenal gland that is part of the sympathetic nervous system secretes epinephrine and norepinephrine | adrenal medulla
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| in the adult adrenal gland what are the divisions and what do they each make | Zona Glomerulosa- Aldosterone
Zona fasciculata- Cortisol
Zona Reticularis- androgens
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| What are the cells that make up the adrenal medulla | pheochromocytes- large columnar cells with large nuclei and vesicles containing norepi and epi
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| What two zones of the adrenal cortex does ACTH regulate | zona fasciculata, and reticularis
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| What is the diurinal pattern of ACTH secretion caused by stimulation from CRH | diurinal rythym is peak before awakening and a decline as the day progresses
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| What is the feeback loop from products of adrenal cortex | negative feedback loop where cortisol inhibits synthesis and release of CRH and ACTH
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| What stimulates zona glomerulosa to secrete aldosterone | renal juxtaglomerular apparatus and the renin-angiotensin system
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| What is the universal precursor for all adrenocortical hormones | cholesterol
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| What converts cholesterol to pregnenolone | enzyme P450scc
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| What is the rate limiting step in producing adrenal hormones | transporting cholesterol into the mitochondria and converting it to pregnenolone
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| what effect will deficiency in any of the hydroxylation enzymes of the adrenal cortex cause | back up of precursors and deficiency in primary hormones
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| What effect does ACTH have on secretion of aldosterone | minimal effect on secretion of aldosterone
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| What is the primary regulator of synthesis and secretion of aldosterone | renin-angiotensin system (angiotensin II)
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| What is the renin-angiotensin system | blood pressure/volume is low kidney secretes renin which stimulates production of angiotesnsin I. Angiotensin I is converted in the lung by Angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II causes vasoconstriction
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| What are the two signals to secrete aldosterone | angiotensin II and excess sodium
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| what is the effect of aldosterone on the distal tubule of the kidney | stimulates sodium retention and potassium excretion or hydrogen ions
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| What is deoxycorticosterone | precursor of Alodsterone that stimulates potassium secretion but doesn't cause as much sodium retention. Release Stimulated by rise in serum potassium
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| What are the effects of cortisol on insulin, lipids and proteins | counteracts insulin- increase blood glucose by stimulating gluconeogenesis, glycogen breakdown in liver
promotes break down of lipids (fat distributes to 7th vertebrae buffalo hump)
promotes break down of proteins (long term muscle wasting and weakness)
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| What are the effects of cortisol on gastric secretion, water fluids, and the immune system | stimulates gastric acid secretion, acts as a water diuretic hormone retain potassium causing weakness and alkalosis, weakens immune system via negative feedback on interleukin-1
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| What effect does cortisol have on allergies | Cortisol is an anit-inflammatory/Anti-Allergy by reducing histamine secretion and stabalizing lysosomal membranes
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| What effect does cortisol have on bone | decreases bone formation and increases bone resorption favorin osteoporosis in long term use
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| What does cortisol cause with eosinophils | eosinophilia
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| what does cortisol cause with heart | increases cardiac contractions
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| Primary precursor of natural estrogens | dehydroepiandrosterone
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| steroid produced by the testes adrenal cortex and ovaries converted to testosterone and other androgens parent structure of estrone | androstenedione
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| A sex hormone that enhances increase in muscle mass and stimulation of bone growth. Stimulates axillary and pubic hair growth | testosterone
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| more potent form of testosterone causes development of secondary sex characteristics such as facial hair, deepening voice, hypertrophy of sebaceous glands | dihydrotestosterone
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| What stimulates release of adrenal medulla hormones | release stimulated by acetylcholine from nerve endings.
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| What are the effects of norepi | vasoconstricts most arterioles resulting in increase in B/P decreases cardiac output
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| What are the effects of epi | vasoconstricts arterioles in the skin causes vasodilation of blood vessels to liver and muscles
increases cardiac output
decreases intestinal motility
stimulates glycogenolysis
increases irritability of CNS
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| What are catecholamines | Norepi and epi
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| How are catcholamines removed from body | metabloized in liver by orthomethylation and deamination then kidney secretes metabolites (metanephrine, normetinephrine, and vanyl mandelic acid VMA)
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| What is Conn's Syndrome | primary hyperaldosteronism caused by adrenal adenoma producing excess aldosterone
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| What causes secondary hyperaldosteronism | low perfusion states
fibrosis of kidney
excessc licorice ingestion
liddle's syndrome
bartter"s syndrom
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| what is liddle's syndrome | dysregulation of epithelial Na+ channels due to genetic mutation causes secondary hyperaldosteronism
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| What is Bartter's syndrome | defect in the ascending limp of loop of henle where kidney doesn't respond to aldosterone causing secondary hyperaldosteronism
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| What can cause low perfusion states leading to secondary hyper aldosteronism | CHF, Cirrhosis, nephrotic syndrome and renal artery stenosis
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| What are the s/sx of excess aldosterone | mild to severe hypertension may present as headache or stroke
fatigue, parasthesias or paralysis
polyuria
nocturia
polydipsia
metabolic alkalosis
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| What are the diagnostic test results for excess aldosterone | Hypernatremia- ↑ increase serum sodium
hypokalemia-↓ serum potassium
hyperaldosterone- ↑ serum aldosterone
hyporeninism- ↓ serum renin level
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| What are the confirmatory tests for primary aldosteronism | saline infusion- should decrease renin and aldosterone primary aldosteronism there will be no decrease in aldosterone level
CT scan- should so adrenal tumoer
Adrenal vein cath- samples from each adrenal vein. vein with heighest level of aldosterone =tum
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| What is the Tx fro excess aldosterone | control hypertension- ace inhibitors
spironolactone- potassium sparing diuretic blocks action of aldosterone it also effects adrogen receptors
Surgical excision of tumor (must treat
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| What are the side effects of spironolactone | gynecomastia, menstrual irregularities, testicular atrophy, ataxia, erectile dysfunction, drowsiness and rashes.
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| What is the Tx fro excess aldosterone | control hypertension- ace inhibitors
spironolactone- potassium sparing diuretic blocks action of aldosterone it also effects adrogen receptors
Surgical excision of tumor (must treat
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| What are the side effects of spironolactone | gynecomastia, menstrual irregularities, testicular atrophy, ataxia, erectile dysfunction, drowsiness and rashes.
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| what is cushings syndrome | excess cortisol production by an adrenal adenoma
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| What are the s/sx of cushings syndrome | rapid weight gain (centripital obesity, buffalo hump, Moon face)
excess sweating
telangiectasia
hirsutism
polyuria/dypsia
hypertension
insulin resistance- hyperglycemia
GI problems
Osteoporosis
Opportunistic infections
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| How do you dx excess cortisol | 24 hour urine cortisol test confirm with plasma cortisol level and ACTH level
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| What would high Serum ACTH in conjuction with excess cortisol indicate | ectopic cushing's syndrome (lung tumor secreting cortisol)
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| What would Low ACTH with excess cortisol indicate | adrenal adenoma
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| HOw does high dose of dexamethasone help dx excess cortisol | dexamethasone is synthetic steroid that is similiar to cortisol. It reduces ACTH in normal people leading to decrease in cortisol. If cortisol remains normal you probably have an adrenal adenoma
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| what imaging technique would you use to confirm location of adrenal tumor | CT scan
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| what is the tx for cortisol excess | reduce exogenous corticosteroid use if caused by medicine
medical therapy to control symptoms to minimize surgical risk
surgical excision to remove adrenal tumor
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| What causes adrenal medulla hormone excess | chromaffin cell tumor called a pheochromocytoma 90% occur in adrenal medulla the rest found along sympathetic chain, 90% benign
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| Associated with familial MEN-II syndrome or MEN III | MENII=hyperparathyroid + medullary thyroid cancer + pheochromocytoma
MEN III= medullary thyroid cancer, Marfan's syndrome, neurofibromatosis, and pheochromocytoma
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| What are the s/sx of pheochromocytoma | looks like hyperthyroid
headaches
paplitation/tachychardia
refractory hypertension
sweating
anxiety
tremors
constipation
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| How do you dx pheochromocytoma | 24 urine collection looking for metanephrines, catecholamines and VMA collected on day with sympotms.
Patient also has to be off anti hypertensives and anxiety meds
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| what is the confirmatory test for pheochromocytoma | clonidine suppression test IV given night AM draw baseline catechols give clonidine redraw catechols after 3 hours
normal: clonidine suppresses catechols
Pheo: No suppression of baseline catechols
Hyperthyroid: clonidine suppresses catechols
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| after positive clonidine test what should be done | radiographic imaging to locate and find tumor
MRI T-2 weighted shows pheo as hyperdense structure
IF MRI is negative do an MIBG test or Octreotide test
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| what is the tx for pheochromocytoma | SURGERY-
pretreat with phenoxybenzamine followed by beta blockers. Post operative give fluid replacment to control hypotension
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| Failure of the adrenal gland leads to what type of adrenal insufficiency | Primary Adrenal Insufficiency
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| What are common causes of primary adrenal insufficiency | autoimmune addison's disease
infections-TB, histoplasmosis, cryptococcus aids
Adrenal Hemorrhage
infiltrative disease- amyloidosis, sarcoidosis
Adrenoleukodystrophy
congenital adrenal hyperplasia
metastic tumors
medication
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| What type of adrenal insufficiency would processes outside of the gland cause | secondary adrenal insufficiency
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| What are some common causes for secondary adrenal insufficiency | chronic glucocorticoid use
pituitary infections
hypothalamic/pituitary tumors
hemochromatosis
sheehan's syndrome
trauma
iatrogenic- surgery or radiation damage to pituitary
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| What would be the s/sx of adrenal cortisol insufficiency | hypotension
tachycardia
weight loss
hyperpigmentation
hyponatremia
hypoglycemia
nausea, vomiting, anorexia
hypercalcemia muscle and joint pain
fever
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| What would be the s/sx of adrenal aldosterone insufficiency | hypotension
tachycardia
dehydration
salt craving
disturbed renal functioning
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| What would be the s/sx of adrenal medulla deficiency | hypotension because no vascular constriction due to lack of catecholamines
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| Why do you need to diagnose adrenal insufficiencies quickly | hypotension, tachycardia, weakness, anorexia are life threatening
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| How do you diagnose adrenal insufficiency | 8:00 am plasma cortisol
check serum electrolytes
check ACTH level
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| HOw do you confirm adrenal insufficiency | ACTH stimulation test
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| what is the ACTH stimulation test | done ot test adrenal insufficiency give ACTH then measure cortisol at 0, 30, 60 minutes if cortison doesn't rise primary adrenal insufficiency
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| What does the metyrapone test aid with in confirming adrenal insufficiency | rules out secondary adrenocortical insufficiency
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| What would CRH stimulation test help confirm | helps determine if adrenal insufficiency is tertiary or secondary.
Give CRH then Check ACTH ACTH goes up it is tertiary if ACTH is absent or subnormal it is ACTH problem so secondary adrenal insufficiency
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| What is the treatment for adrenal insufficiency | replace cortisol- via hydrocortisone if patient is under stress increase dose
replace mineralcorticoids if necessary
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| What is congenital adrenal hyperplasia what is commonly seen with CAH | any one of several autosomal recessive diseases that cause mutations in enzymes in producing cortisol from cholesterol most individual are deficient in sex steroids and have altered sex charachteristics
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| What is the primary enzyme effected in congenital adrenal hyperplasia | 21-hydroxylase deficiency
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| What are s/sx of congenital adrenal hyperplasia | ambiguous genitalia in females
vomiting
early rapid growth of pubic hair
precocious puberty or failure of puberty
excessive facial hair, virilization menstrual irregularities
infertility
hypertension
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| What would be seen in patient w/ congenital adrenal hyperplasia of 21-oh deficiency | high levels of 17-oh progesterone (precursor)
High levels of DHEA
High levels of urinary 17-ketosteroids
Low levels of aldosterone and cortisol
X-ray will show bone age older than normal for person's age
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| What would be seen in patient w/ congenital adrenal hyperplasia of 11-oh deficiency | Elevated 17OH-progesterone
Elevated serum DHEA level
Elevated urinary 17-Ketosteroids
Low Aldosterone and Cortisol levels
but you wouldn't have problems of low aldosterone because you would have DOC precursor of aldosterone that has similar effects
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| Very aggressive and often fatal form of adrenal cancer | primary adrenal cancer
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| how do you dx primary adrenal cancer | elevated 24 hour unrine cortisol w/ decreased ACTH elevated serum DHEA-s Fine needle aspiration
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| how often will you see adrenal masses on CT scans of the abdomen when taken for other reasons | 1% of all abdomen CT scans will reveal adrenal masses must do a complete workup to rule out adrenal cancer
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| If you find an adrenal mass on an X-Ray what do you first look for and what tests will you run | is the tumor hormonally active
cortisol excess test
Aldosterone excess test
Catecholamine excess
Fine needle aspiration to determine metastatic of infiltrative
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| What would you do if you found the adrenal mass was cancerous | Adrenalectomy
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| Disorder of cortisol secretion with Increased plasma cortisol and DECREASED ACTH | primayr hypercortisolism or cushing's SYNDROME
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| Disorder of cortisol secretion with Increased plasma cortisol and INCREASED ACTH | secondary hypercortisolism or cushing's DISEASE
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| iDisorder of cortisol secretion with lower Plasma Cortisol & INCREASED Plasma ACTH | Primary Hypocortisolism: (Addison's disease)
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| Disorder of cortisol secretion with lower Plasma Cortisol & DECREASED Plasma ACTH | Secondary Hypocortisolism: (pituitary tumor)
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