Endocrine Hypertension

Question 1

What is the definition of hypertension?

Answer 1

Systolic BP: >140, Diastolic >90

In two or more visits after the initial screen

Question 2

At what age do we stop using 95% percentile as the definition of hypertension in children? What is this definition?

Answer 2

Children aged 13+

> 130 systolic or >80 diastolic is HTN

Question 3

What is primary vs secondary hypertension and what are the three endocrine causes of hypertension?

Answer 3

Primary - 85%, also known as essential hypertension, no known etiology

Secondary - 15%

1. Renovascular hypertension
2. Pheochromocytoma
3. Primary aldosteronism

Question 4

What are presentations of hypertension which make you lean more towards an endocrine cause than primary / essential hypertension?

Answer 4

1. Severe / resistant HTN (refractory after 3+ meds)
2. Young onset (<30), or rapid old onset
3. Hypertension with spontaenous hypokalemia (hyperaldosteronism)
4. Episodic HTN - pheochromocytoma
5. Characteristic physical exam findings

Question 5

What are characteristic physical exam findings for primary aldosteronism causing hypertension?

Answer 5

Often due to hypokalemia, there are characteristic physical exam findings:

1. Neuromuscular irritability
2. Muscular weakness (inability to increase blood flow to muscles)

Question 6

What physical exam findings are associated with pheochromocytoma?

Answer 6

1. Cold, clammy hands - peripheral vasoconstriction

2. Cafe au lait spots - if associated with NF-1

Question 7

What physical exam finding is associated with renovascular hypertension?

Answer 7

Abdominal bruit -> if HTN is caused by renal artery stenosis

Question 8

What is the most common cause of secondary hypertension? What is the threshold at which this occurs and what are the two subtypes?

Answer 8

Renal artery stenosis
-> occurs at greater than 75% stenosis

1. Atherosclerotic - usually elderly patients, 2/3
2. Fibromuscular dysplasia - usually young women, 1/3

Question 9

What are the two types of fibromuscular dysplasia and which is more common? Where in the renal artery does this occur?

Answer 9

1. Medial fibroplasia -> much more common (80%)
2. Intimal fibroplasia

Occurs usually in distal renal arteries -> string of beads appearance

Question 10

When will renin be high vs not in renovascular hypertension?

Answer 10

Unilateral - can be high or normal, as contralateral kidney will decrease renin production -> choose to treat via clinical index of suspicion

Bilateral - will be high, along with increased BUN / creatinine

Question 11

What is the gold standard of renovascular hypertension diagnosis and what is done to treat? Is it effective?

Answer 11

Gold standard: Renal angiography

• > treat with angioplasty with stent placement
• > very effective in fibromuscular dysplasia, moderately effective in atherosclerosis (restonosis occurs)

Question 12

Where in the renal artery is fibromuscular dysplasia vs atherosclerotic stenosis?

Answer 12

Fibromuscular dysplasia - distal renal artery segments

Atherosclerotic disease - proximal segments (near branch points from aorta)

Question 13

What is the medical therapy for renovascular hypertension?

Answer 13

ACE inhibitors (except in bilateral renal artery stenosis)
or
ARBs (i.e. valsartan)

mainstay due to pathogenic mechanism

Question 14

When is surgery preferred over medical therapy for renovascular HTN?

Answer 14

Recent onset HTN (<5 years), particularly younger patients

Intolerant to medical therapy

Recurrent flash pulmonary edema or refractory heart failure

Question 15

Is hypokalemia required for primary aldosteronism? What can precipitate it?

Answer 15

No! In fact, most patients are not hypokalemic because of the body’s potassium conservation mechanism

Diuretics can precipitate it however -> diuretic-induced hypokalemia is a common way of diagnosing

Question 16

Does primary aldosteronism present with peripheral edema? How?

Answer 16

No -> aldosterone escape mechanism.

Spontaneous diuresis occurs to excrete sodium to normal levels and limit expansion of extracellular volume by release of atrial natriuretic peptide (ANP) -> released in response to distention

Question 17

What is typically used as the screening test for primary aldosteronism?

Answer 17

PAC/PRA ratio
Plasma aldosterone concentration / plasma renin activity

If ratio >20, it has 100% sensitivity, because aldosterone will be very high compared to renin.

Question 18

How is definitive diagnosis of primary aldosteronism made? What should be done if this test is positive?

Answer 18

Salt-loading. Salt load for 3 days
-> urinary sodium will be high, but aldosterone will be non-suppressed.

If test is positive -> order CT scan of adrenal to look for abnormality

Question 19

What should be done for patients with a normal adrenal CT following a positive test for primary aldosteronism? How about if you are over age 40 and CT is positive?

Answer 19

Same test for both: adrenal vein aldosterone sampling -> see which adrenal gland is overproducing.

Over age 40, non-functioning adenomas are common -> need to sample adrenal vein to be sure gland is overproducing

Question 20

What drugs are used for medical treatment of primary aldosteronism and which is preferred?

Answer 20

Spironolactone and Eplerenone

Spironolactone is preferred -> longer halflife and greater antagonist activity

Eplerenone - fewer anti-androgen side effects, but more expensive

Question 21

What is the classic triad of pheochromocytoma?

Answer 21

Headache
Sweating
Palpitations

Question 22

Does pheochromocytoma always present with hypertension? What is the patternof HTN?

Answer 22

95% of people will have hypertension

50% will have intermittent (episodic) HTN, but 50% have sustained HTN as well.

5% of people remain normotensive due to adrenoceptor downregulation.

Question 23

What defines a low vs high risk patient for pheochromocytoma?

Answer 23

Low - resistant HTN with hyperadrenergic spells, and adrenal mass w/o characteristics of pheo

High - Previously resect pheo, FHx of pheo, genetic syndrome related to pheo (i.e. MEN2), adrenal mass with high suspicion on MRI/CT

Question 24

What testing should be done for pheochromocytoma in low and high risk patients? Which one should children have done?

Answer 24

Low risk - Urinary fractional metanephrines -> higher specificity, lower sensitivity (i.e. patients with minimal acute symptoms unlikely to have major problems)

High risk - Plasma fractional metanephrines -> higher sensitivity for when it matters, but lower specificity (many false positives)

Children -> do plasma metanephrines since much easier

Question 25

What is the imaging study of choice for pheochromocytoma?

Answer 25

MRI - increased brightness on T2 MRI, best overall test

CT - can be used, but high rate of misdiagnosis of incidentaloma

MIBG radionucleotide scan -> used only for extra-adrenal localization

Question 26

What is the treatment sequence for pheochromocytoma?

Answer 26

1. Alpha blockade - irreversible, i.e. phenoxybenzamine

followed by:

2. Beta blockade
   - > reversing this order could cause hypertensive crisis

then

3. Tumor resection

Question 27

When should germline screening for pheochromocytoma be done?

Answer 27

Young age
Bilateral pheos
Unilateral pheo with FHx
Paraganglioma present

Question 28

What germ lie mutations are associated with pheochromocytoma?

Answer 28

NF-1 -> neurofibromatosis 1
VHL -> von Hippel Lindau
RET -> MEN2A and 2B

Question 29

What is pseudopheochromocytoma, and what must be ruled out?

Answer 29

Disease of paroxysmal hypertension caused by increased sympathetic tone

Rule out:
Labile HTN
Panic Disorder