Week 2: endocrine hypertension

Question 1

Secondary forms of HTN

Answer 1

15% of HTN is secondary, 2-3% of which with endocrine HTN

• mainly primary aldosteronism (2%) and pheochromocytoma (0.5%)
• other endocrine causes of HTN: thyroid, Cushing’s, Acromegaly, CAH, enzymatic defects, licorice

Question 2

Licorice induced HTN

Answer 2

• licorice inhibits 11b-HSD2, preventing conversion of cortisol to cortisone
• cortisol binds to mineralocorticoid receptor, leading to Na retention, K wasting, and HTN

Question 3

Overview of aldosterone regulation and feedback

Answer 3

• if blood volume falls and renal perfusion decreases, sensed by macula densa via decreased Na+ and also via stretch by JG cells
• JG cells release renin–>AngI->AngII->aldosterone release
• aldosterone via ENac, increases Na retention to increase circulating blood volume

Question 4

Consequences of Aldosterone excess

Answer 4

1. Hypertension- volume dependent
2. hypokalemia due to K+ wasting
3. Eunatremia
   - with rise in intravascular blood volume, leads to detection of stretch and release of ANP
   - naturesis and Na+ dumping
   - leads to normal serum Na levels
4. Alkalosis
   - enhanced H+ excretion

Question 5

Clinical features of primary hyperaldosteronism and causes

Answer 5

Features
-hypokalemia, alkalosis, HTN
-low plasma renin, high serum aldosterone
Disorders
-aldosterone producing adenoma (35%)
-primary adrenal hyperplasia (65%)
-adrenocortical carcinoma

Question 6

clinical features and causes of secondary hyperaldosteronism

Answer 6

Features
-hypokalemia, alkalosis, HTN
-high plasma renin, high serum aldosterone
Disorders
-renal artery stenosis
-renin secreting tumor
-malignant HTN
-chronic renal disease

Question 7

Evaluation of suspected hyperaldosteronism

Answer 7

1. discontinue interfering medication: diuretics and ACE I
2. take supine renin and aldosterone levels
   - distinguish primary and secondary
   - primary: 30:1 aldo to renin ratio, as long as aldo levels above 15
3. Adrenal CT scan
   - unilateral nodule–>laproscopic adrenalectomy
   - nodular hyperplasia–>pharmacologic therapy

Question 8

With elevated serum aldosterone and undetected renin levels, how to distinguish between adenoma vs hyperplasia?

Answer 8

1. 18-hydroxycorticosterone (molecule before aldosterone)
   - adenoma>50ng/dl
   - hyperplasia<50ng/dl
2. Posture test: stand up for 30 mins, activates RAS system
   - adenoma: stable aldo, and 18OHB levels
   - hyperplasia: rise in aldo and 180OHB levels

Question 9

Diagnosing secondary hyperaldosteronism and treatments

Answer 9

1. renal artery stenosis
   - use renal doppler
   - Rx with dilatation of stenotic lesion
2. renin secreting tumor
   - imaging
   - resection of lesion

Question 10

pheochromocytoma, epidemiology

Answer 10

• rare tumors that cause pressor type HTN by releasing large amounts of catecholamines
• suspect in patients with new HTN at extremes of ages and 30-50 yo
• 90% solitary, 10% bilateral
• Familial: 50% bilateral and associated with MEN

Question 11

Workup of pheochromocytoma

Answer 11

1. 24 hour urine and/or blood test
   - test for metanephrine and normetaneprhrine, metabolites of Epinephrine and NE respectively because so many things cause increase in Epi and NE levels such as blood draw
   - urine fractionated catecholamines
   - 2-3x above normal for urine tests , and significant increase in plasma levels indicates pheochromocytoma
2. If 24h urine and plasma tests normal, repeat during paroxysm
   - if normal again, end of eval
   - if elevated do imaging
3. anatomic imaging with CT or MRI
   - secondary test is 123I MIBG scan

Question 12

Clinical features of pheochromocytoma

Answer 12

• HTN that is labile and paroxysmal
• sever throbbing headache
• profuse sweating
• palpitations
• anxiety
• nausea w/ or w/o emesis
• abdominal pain

Question 13

Rx of pheochromocytoma

Answer 13

• surgical removal
• pre-op alpha blockage, then beta
• laproscopic adrenalectomy
• but tends to recur

Question 14

MEN and pheochromocytoma

Answer 14

• RET gene on chromosome 10q11.2
• encodes membrane tyrosine kinase receptor
• MEN2A: TAP, RET protooncogene codon 634
• MEN2B: MAT (medullary thyroid cancer, mucocutaneous, pheochromocytoma), RET protooncogene codon 918