Endo - 2-1 Adrenal Cortex

Front 1

What does adrenal cortex secrete?

Back 1

cortisol, aldosterone and other mineralocorticoids, and weak androgens.

Front 2

ACTH as a trophic factor

Back 2

Deficiency results in atrophy of the zona fasciculata and reticularis.

Front 3

Synthesis of ACTH

Back 3

In corticotroph cells of ant pit as part of proopiomelanocortin.

Cleavage gives rise to ACTH, endorphins, melanocyte stimulating hormone.

Front 4

What stimulates ACTH release?

Back 4

CRF and vasopressin.

Front 5

Best time to test for adrenal insuff and adrenal hyperfun

Back 5

insuff - 8AM (when levels should be high)

hyperfunction - midnight (when levels shoul dbe low)

Front 6

Cortisol and mineralocorticoid receptor

Back 6

Has high affinity, but 11-OHSD enzyme converts cortisol to cortisone which is inactive.

So 11-OHSD protects mineralocort receptor from being overwhelmed by the much higher [] of cortisol compared to aldosterone.

But in case of chronic cortisol excess, you get mineralocorticoid effects (sodium retention and HTN)

Front 7

Aldosterone and glucocrticoid receptors

Back 7

Has high affinity, but the [] is very very low.

Usually don't ever get the [] high enough to get glucocort effects (even in pathological states).

Front 8

Dexamethasone

Back 8

pure, potent glucocorticoid (high affin for receptor). Has lower affin to transcortin so more of it is free. And has long half-life.

Prednisone is the inactive form of this.

Front 9

Metab of cortison

Back 9

Measure metabolism with [] of 17-hydroxysteroids.

Front 10

Mechanism of endogenous glucocorticoids - why we have them

Back 10

the prevent body's normal reactions to stress from becoming overactive and harmful.

anti-inflamm, suppress ADH, suppress PGs, bradykinin, cytokines, prevent hypoglycemia (less uptake of glucose, less insulin secretion, stimulates glucagon secretion), suppression of neuropeptides.

Front 11

Sx of chronic adrenal insuff

Back 11

This is Addison's disease

Fatigue, loss of app, weight loss, abdon complaints, lightheadednes.

Front 12

Acute adrenal insuff sx

Back 12

fever, CV collapse refractory to pressor support.

Front 13

Waterhouse-Friderichsen's syndrome

Back 13

Rapid damage to adrenal glands (e.g. hemorrhagic destruc) in pts with severe bacterial sepsis or coagulopathies.

Front 14

Mineralocorticoid deficiency in prim (adrenal) or secondary (pit/hypo) adrenal insuff?

Back 14

Only in primary.

With secondary, AII can still stimulate aldosterone.

Front 15

Androgen def sx seen in men or women with adrenal insuff?

Back 15

women

with men, the testes still function and compensate.

Front 16

Manifestations of aldosterone deficiency

Back 16

Hypovolemia (can't conserve sodium) --> postural hypotension, weight loss, inc ADH, hyponatremia, increased renin.

Impaired renal sec of potassium and H+ --> hyperkalemia and mild metabolic acidosis.

Front 17

Sx of primary vs. secodnary adrenal insuff

Back 17

With secondary, you will not have hyperpigmentation (less ACTH), will have hypothyroidism, hypogonadism, GH def, and also sx related to mass lesion (HA, visual dist, diabetes insip, CN palsies).

Front 18

3 factors leading to impaired renal water handling in pt with adrenal insuff

Back 18

1. hypotension bc poor vasc tone.

2. mineralocorticoid def impairs kidney's abil to form free water in distal nephron (only with primary adrenal insuff). This also gives hyperkalemia.

3. inc ADH to reliev hypotension which leads to hyponatremia.

So hyperkal + hyponat = primary.
only hyponat = secondary.

Front 19

Cosyntropin test

Back 19

For adrenal insuff.

Reponse of adrenal glands to exogenous ACTH.

If primary adrenal insuff is there, exog ACTH will not stimulate cortisol secretion. This test will also be abnormal if secondary adrenal insuff was there for so long that adrenal glands atrophied.

THIS CAN BE PERFORMED IN IMMEDIATE CRISES!!!

Front 20

Hypoglycemic challenge

Back 20

For adrenal insuff.

Hypoglycemia stimulates release of CRF, ACTH and cortisol.

But if there is no response of cortisol (check GH too...) and adrenal glands are normal, the issue is with pit or hypothal.

This is risky to do with a pt who has primary adrenal insuff (life-threatening adrenal crisis)

Front 21

tx of primary adrenal insuff

Back 21

glucocort and/or mineralocort admin

Can't monitor cortisol or ACTH levels (short half-life). Need to monitor based on sx.

Should rx minimal dose to avoid SEs.

With stress, need to increase dose.

wear medic-alert bracelet.

Front 22

Sx of best PPV with glucocort excess

Back 22

proximal muscle weakness/atrophy, osteoporosis in males or premeno women, spont bruising, hypokalemia (will have this if pt is on diuretics).

Front 23

What does aldosterone do?

Back 23

Retains Na+ and H2O. Secretes K+

Front 24

Mild Cushing's syndrome present similarly to...

Back 24

PCOS, metabolic syndrome or obesity with diabetes.

Front 25

Hallmark of Cushing's syndrom

Back 25

lack of normal diurnal variation of cortisol levels.

Front 26

Can an abnormal overnight dexamethasone suppression test establish dx of Cushing's Syndrome?

Back 26

No - relatively low specificty.

Note - using dexameth because it won't be read as cortisol in the assay the next morning. But prednisone or prednisolone would.

Front 27

21-hr urinary free cortisol

Back 27

for cushing's

need to measure creatinine too. to make sure collection was complete.

good to confirm the dx (high specificity).

Front 28

paradigm to confirm dx of cushings

Back 28

obrain midnight salivary cortisol or do dexameth supp first, then if either of these is abnormal, do 24-hour UFC.

Front 29

Gold-standard to dx Cushing's

Back 29

low dose dexamethasone suppression test.

cumbersome - many consec days of 24-hr urine collection.

pt with Cushing's will not suppress cortisol in response to dexamethasone.

Front 30

Things that give false + in dexameth overnight test

Back 30

stress
depression
failure to take the dex at the right time
also rx phenytoin (induces metab of dexamethasone)
estrogen, pregnancy or obesity raise transcortin and make the cortisol appear higher than it actually is.

Front 31

Cushing's DISEASE

Back 31

Cushing's syndrome resulting from abnormalities of pituitary or rarely the hypothal.

Thsi si the most cmomon cause of cortisol excess.

Front 32

Nelson's syndrome

Back 32

When Cushing's DISAESE is tx with bilateral adrenectomy and there is an increase in size of pituitary gland because of the lack of feedback inhibition.

Note - treating by removing adrenals is way off. Problem was at the pituitary.

Front 33

Ectopic ACTH prod

Back 33

Small cell CA of the lung and bronchial carcinoids are most common agents.

Sx suggested by occurence of Cushing's in older male, sx of brief duration, hyperpigmentation, hypokalemia and alkalosis, minimal Cushingoid features (because of short duration of the disease)

Front 34

Do ACTH secreting pituitary tumors respond to CRF?

Back 34

Yes

But ectopic ACTH producers do not.

Front 35

Exception with bronchial carcinoid tumors

Back 35

Pts with this tumor will often suppress cortisol production in response to ectopic ACTH.

But usually, ectopic

Front 36

How to differentiate pituitary from ectopic Cushing's syndrome

Back 36

Gold standard for diagnosis - petrosal sinus sampling.

Venous drainage from pituitary is in these sinus and lateralization remains.

CRF injected. with pituit, ACTH will increase. With ectopic, it will not.

Gradient in ACTH of 3-fold btwn petrosal sinus and periph vein is indicative of pituitary issue.

This can also lateralize the tumor.

Front 37

Tx of Cushing's

Back 37

Surgical removal of the pituit tumor, adrenal tumor, or ectopic source of ACTH.

If not possible, then do drug therapy that blocks adrenal hormone synthesis.

Front 38

Conn's syndrome

Back 38

Adrenal tumor secreting mineralocorticoids (results in HTN and hypokalemia).

Front 39

Where do pheochromocytomas arise from?

Back 39

adrenal medulla (not cortex).

Front 40

Effects of prescribed glucocorticoids

Back 40

Stim gluconeogenesis, inhib protein/FA synth, impairs Ca++ abs from intestine and inhibits osteoblast activity, anti-inflammatory.

Front 41

How to minimize SEs of glucocorticoids

Back 41

Caloric restriction, supplemental Vit D, calcium and bisphosphonate therapy to counter the adverse effects on bones.

Front 42

Last page of notes has a chart of drugs

Back 42

do we have to know it?

Front 43

Which zones for which end-products?

Back 43

Reticularis - sex steroids

Fasiculata - cortisol

Glomerulosa - aldosterone.

Front 44

Stain very characteristic for pheochromocytoma lesion

Back 44

synaptophysin immunoreactivity

Front 45

What to do when you find an adrenal mass in a healthy person?

Back 45

Urinary collection of manyllmandelic acid (VMA) and metanephrines to rule out occult pheochromocytoma.