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2. adrenals


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The 2 componenets of the adrenal gland are:
1. Medulla
2. Cortex
What does ea component produce?
Medulla: epi/norepi/dopamine
Cortex: androgens, glucocorticoids, mineralcorticoids.
What are epi/norepi/dopamine known as collectively?
What causes the release of catecholamines?
Sympathetic fibers firing in the adrenal medulla.
What causes the sympathetic fibers to fire and stimulate catecholamines?
Stress, exercise, hypoglycemia, and trauma.
How are catecholamines carried through the body?
Bound to albumin and serum proteins.
What are the targets of catecholamines?
Alpha/Beta adrenergic receptors
Which catecholamine acts on the heart, and how?
Epinephrine - increases HR and contraction force by acting on beta-adrenergic receptors.
Which catecholamine acts on blood vessels and how?
Norepinephrine - constricts BV's and increases resistence and arterial BP.
What other things do epi and norepinephrine do?
-Dilate bronchioles
-Stimulate lipolysis
-Increase metabolic rate
-Promote glycogenolysis
-Dilte pupils, inhibit gastrointestinal digestion.
What is the most common pathology of the adrenal medulla?
Pheochromocytoma - a benign adenoma in its chromaffin cells
What is the #1 neoplasm in kids?
what's a pheochromocytoma often called?
the 10% tumor
What methods are used for detecting pheochromocytoma? (4)
1. Plasma catecholamines
2. Urine catecholamines
3. Urine metanephrines
4. Urine VMA
what is VMA?
Vanillylmandelic acid; the degradation product of norepi and epinephrine.
What is the degradation product of dopamine?
HMA - homovanilic acid
what is another degradation product of epinephrine?
metanephrine (MN)
what is another degradation product of norepinephrine?
normetanephrine (NMN)
what is the more sensitive test for pheochromocytoma?
24-hour urine catecholamines and metabolites.
What are some tips to remember re: catecholamine specimens?
-May need >1 24hr urine collecn
-Measure creatinine to ensure that it's a 24 hr urine.
-Don't add a preservative
-Use plasma for better sensitivity than serum
The catecholamines are amino acid hormones; what is a similar molecule that's more of a neurotransmitter?
what is serotonin?
a monoamine neurotransmitter
what's another name for serotonin?
5-HT; 5-hydroxytryptamine
Where is serotonin made?
-CNS: In serotonergic neurons
-Intestine: enterochromaffin cells
what are some important fucntions of serotonin?
-Sleep regulation
-Smooth muscle releaxation
-Cardiovascular function
-GI/vascular contraction
what type of tumor is most often related to serotonin?
Carcinoid tumor - of the small bowel.
What is 5-HIAA?
a degradation product of serotonin; measuring both of these in urine will indicate carcinoid tumors.
What is the adrenal cortex a factory for?
(corticosteroids that is)
The 4 steroids we're mainly focused on:
1. Estrogens
2. Testosterone
3. Cortisol
4. Aldosterone
what are the corticosteroids synthesized from?
What does aldosterone do?
Acts on kidney distal tubule; increases Na uptake, K excretion. Increases water resorption
What is the ultimate consequence of aldosterone?
Increased extracellular fluid.
What does cortisol do?
Increases and maintains normal blood glucose levels.
How does cortisol work?
-Mobilizes amino acids/fat
-Stimulates liver gluconeogenesis.
-Suppresses immune system
-Promotes lung maturation and surfactant production.
What do the androgens do?
function in sex
What regulates the adrenal cortex in general?
But what feedback regulates aldosterone?
-Increased K
-Decreased Na
-Angiotensin II due to decr renal blood flow
-ACTH is short-term
What suppresses aldosterone?
-High Na
-Low K
What is ACTH much more active in controlling?
What stimulates CHR release?
Physical and mental stress
What regulates the androgens partially?
What is adrenal cortex
Hypo = Addison's disease

Hyper = Cushing's disease
How would you differentiate between Primary adrenal insufficiency and ACTH-dependent?
ACTH primarily controls cortisol, so aldosterone would be less decreased; also ACTH would be decreased in the latter.
What are the diagnostic levels of Cortisol and ACTH for diagnosing hypofunction?
Cortisol: <10 ug/dL
ACTH: >250 pg/mL
and quickly, corticosteroid excess IS?
exogenous glucocorticoid treatment
Screening tests for hyperadrenalism:
-Serum/urine free cortisol
-ACTH levels
How would you know if Cushing's disease was ACTH independent?
-ACTH levels would not be high
-Overnight dexamethasone suppression would not change with high dose.
So what is the confirmatory test for cushing's?
Overnight dexamethasone suppression with high dose will show change because the ACTH is so high it STILL stimulates production.
How does an adrenal tumor affect cortisol, ACTH, and CRH levels?
-Cortisol is increased
-ACTH is decreased
-CRH is decreased
What is mineralcorticoid excess?
What is the name for primary mineralcorticoid excess?
Conn's syndrome
How is Conn's syndrome diagnosed?
By measuring renin and aldosterone levels.
List 5 assays for assessing adrenal function:
1. Cortisol (blood and urine)
2. Aldosterone
3. 11-deoxycortisol
4. 17-hydroxyprogesterone
5. PRA - plasma renin activity
What is 17-hydroxyprogesterone?
the precursor to cortisol
what is 17-hydroxypregnanolone?
the precursor to testosterone
what is progesterone?
the precursor to aldosterone.
How is a low-dose Dexamethosone test done?
1. Draw baseline blood cortisol
2. Give 1 mg Dexameth at 11pm
3. Draw blood at 8am
What are the results of lo-dose dexamethosone testing in:
-normal individuals?
-Cushing's syndrome?
Normal: <3ug/dl serum, <100ug/dl in urine.
CS: >10ug/dl serum, >120 ug/dl in urine.
What is high-dose dexamth suppression useful for?
Differentiating Primary Cushing's (suppression occurs) from 2dary (ACTH stimulated) where no suppression occurs.
RECAP: for cushing's syndrome,
-What are screening tests?
-What are confirmatory tests?
Screens: Urine cortisol and lo-dose DM test.

Confirm: Plasma ACTH, serum cortisol, hi-dose DM test.
What's the principle of the metapyrone stimulation test?
Inhibiting 11-hydroxylase blocks cortisol synthesis (metapyrone inhibits the enzyme)
What metapyrone stimulation results are seen in:
-healthy patients?
Healthy: cortisol levels drop
Cushing's: ACTH increases.

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