Adrenal Diseases Flashcards
how is glucose related to potassium?
if there is low potassium, (hypokalemia) then there is glucose intolerance.
Insulin secretion is dependent on potassium, thus when there is hypokalemia there is decreased insulin secretion and elevated amounts of glucose in blood
hypokalemia is seen with polyuria as well (which is caused by high blood glucose)
** need to know: hyperglycemia, insulin deficiency, hypokalemia - all go together
what ion changes cause polyuria?
hypercalcemia and hypokalemia
Hypokalemia produces defective activation of renal adenyl cyclase and thus, causes nephrogenic DI, ie
polyuria
which drugs cause hypokalemia?
- HCTZ: causes secondary hyperaldosteronism and see hypokalemic alkalosis
- Albuterol –> stimulates release of insulin (catecholamines stimulate insulin release)–> lower serum potassium concentrations
- This release of insulin shifts the potassium into the cells thus lowering the serum potassium level.
- thus can give pt. albuterol to decrease serum calcium levels
Conn’s syndrome
= primary hyperaldosteronism: results in excess secretion of aldosterone
Causes:
- adrenal adenoma (Conn’s syndrome)
- unilateral or bilateral adrenal hyperplasia
- genetic defect with strong effect of aCTH on aldo production (corticosteroid responsive aldosteronism) - would see BP drop when placed on cortisone
- ALDO works on collecting tubule: brings in 2 sodium, and excretes one potassium and one hydrogen = hypokalemic alkalosis
- cause of non-essential hypertension
- no edema d/t production of ANP which counteracts Aldo effect
- AngII and K+ drive the secretion of aldosterone normally
what things cause non-essential HTN?
aldosteronism (Conn’s/BAH)
Increased cortisol (Cushing’s)
Licorice
myxedema (hypothyroidism) + hypercalcemia
pheo
congenital adrenal hyperplasia
hyperthyroidism
testing for primary aldosteronism?
- pt. has HTN and hypokalemia
1. Plasma renin acvitiy (PRA) to plasma aldo concentration (PAC) - if PRA and PAC is high (ratio is 10): investigate secondary hyperALDO
- diuretics, renovascular HTN, renin-secreting tumor,
- if PRA is low and PAC is high (PAC-PRA ratio >30, with PAC >20)
- investigate for primary aldosteronism
- if PRA and PAC are decreased
- investigate for congenital adrenal hyperplasia, Cushings, Liddle’s syndrome, 11-beta-HSD deficiency (licorice)
definitive testing for primary aldosteronism?
- test renin at 8-10 am (normal/high renin disproves aldosteronism)
- if PRA is low, , stand up for three hours and look at the plasma A/R ratio: aldosterone(ng/dL): renin(ng/mL/h) > 30 = probable aldosteronism
( If PRA is undetectable, K is low, and PAC > 30 ng/dL = primary aldosteronism.)
- if A/R ratio is increased, CONFIRM with Na loading and 24 hour urine for aldosterone (if urine aldosterone over 20 mcg/24 h indicates primary aldosteronism)
- If the urine aldosterone is increased, perform adrenal CT or adrenal vein sampling (affected side/unaffected side exceeds 4:1) to distinguish hyperplasia from adenoma
how to differentiate b/w BAH and adenoma in primary aldosteronism? treatment?
** postural stimulation test: draw plasma aldosterone at 8 AM and after 4 hours upright
Unilateral adenoma: has baseline aldosterone of >20 that does not rise in upright position
- tx = surgery
bilateral hyperplasia has baseline <20 that RISES during upright posture (this is b/c hyperplasia is still under renin/ANG system and will be affected by posture changes)
- tx = spironolactone, eplerenone (aldo antagonist)
what does licorice do to cause HTN?
Licorice (glycrrhizinic acid) inhibits HSD2 and thus allows cortisol to drive the mineralocorticoid receptor with resultant hypertension (of course, renin and aldosterone levels will be low).
= same as 11-beta-HSD deficiency
** renin and aldo will BOTH be low if this is the driving cause!
Liddle’s syndrome
HTN w/ low K+
- low renin AND low ALDO
- hypokalemic alkalosis
= gain of function mutation at the principle cell: sodium channel is always on, bringing sodium back into the cell and excreting potassium
= pseudohyperaldosteronism
Gitelman’s syndrome
= like thiazide diuretic
- blocks sodium reabsorption in DCT, so later reabsorbed in CD (results in hypokalemic alkalosis w/ hypocalciuria)
- also see mm. cramps, hypocalciuria
- seen in adolescence
- see increased RAAS as bodies way to counteract
Bartter’s syndrome
like a loop diuretic
- results in hypokalemic alkalosis w/ no HTN
- increased renin and aldo
- hypercalciuria
- presents at childhood w/ mental and growth retardation
causes for hirsuitism?
- usually d/t decreased sex hormone binding globulin (i.e. increased free testosterone)
1. decreased estrogen (prolactinoma)
2. insulin
3. GH (similar to insulin)
- usually d/t decreased sex hormone binding globulin (i.e. increased free testosterone)
** or due to excessive activity of 5-alpha-reductase (makes testosterone active)
- pituitary tumors (prolactinoma decreases production of estrogen with decreased SHBG = increased androgens)
- deficiency of 21 hydroxylase (CAH)
- Cushings syndrome (increased secretion of androgens along w/ cortisol)
- idiopathic/familial (increased skin 5-alpha reductase activity )
causes for virilization?
virilzation = hirsuitism (hair growth) + increased mm. mass, clitoromegally, deep voice, libido increased
- ovarian/adrenal tumors: increased LH/FSH –> increased testosterone production
- congenital adrenal hyperplasia - 21 hydroxylase deficiency
Labs usually show:
- ovarian neoplasm: increased testosterone (normal DHEAS and 17 OHP)
- adrenal neoplasm: greatly increased DHEAS (>700)
- CAH: testosterone, DHEAS and 17 OHP are all increased
which labs are done for patients w/ hirsuitism?
testosterone, DHEAS (Androstenedione), 17-OHP
- adrenal neoplasm or CAH: DHEAS > 700
- Polycystic ovary syndrome total testosterone increased (>200)
- CAH- all are increased (17 OHP>500)
tx for hirsuitism?
antiandrogens: spironolactone, flutamide, finasteride, metformin (lowers insulin levels)
different CAH syndromes?
11: increased BP increased virilzation
21: decreased BP, increased virilzation
17: increased BP, no virilization
causes of hyperadrenergic states? (things that look like pheo)
anxiety, acute intermittent porphyria, hypoglycemia, pheo, thyrotoxicosis, sepsis
How does norepinephrine/epinephrine produce:
- neutrophilia?
- hyperglycemia?
- hypotension?
- elevated calcium?
- Mobilization of neutrophils from the vessel walls. (neutrophilia)
- Activation of α 2 receptors on islet β cells with decreased insulin output and increased liver glucose production by β 2 receptors (glycogenolysis and gluconeogenesis).
- Postsynaptic down regulation of α receptors causing less splanchnic and capacitance vessel constriction. Predominance of epinephrine, a beta-adrenergic stimulatory vasodilator, yields tachycardia, and hypotension.
- Calcium is elevated from adrenergic stimulation of the parathyroids (MEN 2), or tumor elaboration of PTHRH
If a given tumor mainly produces norepinephrine, where could it be located?
Only the adrenal produces epinephrine through phenylethanolamine methyltransferase. Thus norepinephrine secreting tumors can be anywhere in the paraganglion chain from the head to the testicles. Epinephrine tumors must be in the adrenals.
If suspect pheo and CT or MRI fails to show an adrenal tumor, what is the next step?*
Why should the nuclear scans be repeated in 3 months?
Whole body scan with *123I-MIBG, 18FDG-PET.
For metastatic or recurrent tumor which may not be initially apparent. Malignant tumors tend to secrete dopamine as well.
10% rules of pheo? signs of pheo?
10% Rule for PHEO: Bilateral Malignant Extra-adrenal Children Calcification
Persistent hypertension Paroxysmal hypertension Postural hypotension (epinephrine, or receptor downgrading) Palpitations Perspiration Pallor Pain – head, chest, abdomen Paresthesias (ap)Prehension Poor heat tolerance and weight maintainance
when to worry about incidentalomas?
have a 25% incidence of containing cancer cells if > 6 cm in size.
- Thus, biopsy is definitely indicated if the size > 6 cm
Preoperative evaluation must include:
- plasma free metanephrines
- 1 mg dexamethasone suppression test (If cortisol suppresses to < 2 mcg/dl, you’ve ruled out Cushing’s)
60% of incidentalomas are associated with some degree of CAH as suggested by an exaggerated 17-OH steroid response to ACTH
