Endocrine HTN (DJ) Flashcards
HTN increases the risk of:
stroke, heart failure, MI, renal failure
Why do we treat essential HTN?
lowering BP = lower risk of diseases associated with HTN
CVA, CHF, MI, RF
How is pre-HTN defined?
SBP = 120-139 DBP = 80-89
*note: these people progress to HTN at a rate of 10%/yr
CV risk is greater in patients with high levels of:
renin
compared to patients with low-renin HTN
BP response to diuretics and CCB’s is better in patients with what type of HTN?
low-renin
BP response to ACEI’s is better in patients with what type of HTN?
high-renin
T/F: Successful trx of essential HTN can be curative
F, trx of the underlying cause of secondary HTN*
What 3 endocrine diseases cause HTN in the majority of patients?
primary hypoaldosteronism
pheochromocytoma
Cushing’s
What are the 2 components of the sympathochromaffin system?
- sympathetic NS (NE)
2. chromaffin tissues, e.g. adrenal medulla (epi)
What is the major end product of catecholamine metabolism? What enzyme produces this?
vanillymandelic acid (VMA) MAO
Because there is a steep concentration gradient for ___, typical plasma levels must be substantially increased to affect BP.
NE
What are pheochromocytoma?
catecholamine-producing tumors comprised of chromaffin cells, which produce labile HTN and paroxysmal symptoms
Why is it important to detect pheochromocytoma?
1) usually curable
2) untreated patients are at risk for a lethal HTN paroxysm
3) 5-10% of them are malignant
4) may be a clue to a familial autosomal dominant syndrome
What malignancies are associated with pheochromocytoma?
multiple endocrine neoplasia:
- -type 2A (hyperparathy + medullary carcinoma of the thyroid)
- -type 2B (multiple mucosal neuromas + medullary carcinoma of the thyroid)
What are 2 conditions that may occur with familial pheochromocytoma?
- von Hippel-Lindau (abn tumor suppression)
2. neurofibromatosis (uncommon)
What clinical symptoms are associated with pheochromocytoma?
- paroxysmal symptoms (HA, diaphoresis, palpitations)
- labile HTN
- family hx
What stimuli may elicit pheochromocytoma symptoms?
positional changes stress abd pressure meds direct pressure applied to tumor
What metabolic features are associated with pheochromocytoma?
increased metabolism
profuse sweating
hyperglycemia
wt loss
What causes glucosuria associated with pheochromocytoma?
catecholamines stimulate hepatic glucose production and inhibition of insulin secretion/action
What hematologic and hemodynamic features are associated with pheochromocytoma?
catecholamine-induced vasoconstriction and plasma volume reduction cause:
- orthostatic hypotension
- elevated hct (volume contraction)
What labs are performed to diagnose pheochromocytoma?
What drug should you use to treat HTN for these labs?
- 24h urine catecholamine (preferred)
- total metanepherines
- plasma catecholamine (but short t1/2)
clonidine–avoid false positives
Where are most pheochromocytoma located?
abdomen (99%) adrenal medulla (90%)
Where are familial pheochromocytoma located?
bilateral adrenals
Treatment of pheochromocytoma?
surgery with pre-op trx with alpha-antagonists (to prevent BP increases during surgery)
How do mineralocorticoids affect the kidneys?
stimulate distal tubules to reabsorb Na+ and excrete more K+ and H+
- increase open Na and K channels
- increase synth of Na/K/ATPase
How do mineralocorticoids affect BP?
increased Na = expanded ECF volume + increased BP
How do mineralocorticoids affect blood levels of Na, K and H?
increased Na
decreases K
decreased H (increased pH)
*evidence that effects on the brain may contribute to HTN
What hormones activate the mineralocorticoid R?
aldosterone (*primary)
cortisol
(note: cortisol in converted to cortisone in renal tubule)
How does inactivation of 11-beta hydroxysteroid dehydrogenase result in apparent mineralocorticoid excess?
enzyme inactivation (via hereditary defect or drug inhibition) prevents conversion of cortisol»cortisone; mineralocorticoid R is then activated by “normal” levels of cortisol
What does mineralocorticoid excess cause?
HTN
hypokalemic acidosis
What does mineralocorticoid excess NOT cause (unexpectedly)?
hypernatremia (regulated by thirst/ADH)
edema (regulated by ANP)
What is primary hyperaldosteronism?
increased aldosterone secretion
**renin and AT are suppressed by negative feedback
What is secondary hyperaldosteronism?
increased renin secretion due to deficient salt intake, decreased ECF volume or decreased kidney perfusion
How is primary hyperaldosteronism diagnosed?
ratio of plasma aldosterone to plasma renin activity
aldosterone»_space;> renin, ratio larger than nml
What is the etiology of primary hyperaldosteronism?
aldosterone-secreting adrenal adenoma (66%)
bil adrenal hyperplasia (33%)
What are the clinical findings in primary hyperaldosteronism?
HTN (due to increased Na)
hypokalemia
How is primary hyperaldosteronism confirmed?
give IV saline; ECF expansion would suppress secretion in nml patient
Clinically, when would you suspect primary hyperaldosteronism?
when a patient has HTN and spontaneously low K
How is primary hyperaldosteronism often treated? Secondary?
- resection (if adenoma), which cures hypokalemia and usually HTN
- aldosterone agonist + anti-HTN drugs
Why is dexamethasone used in diagnostic tests?
produces negative feedback in diagnostic tests but does not interfere with measurement of cortisol
What symptoms is present in 80% of patients with Cushing’s?
HTN
How are mineralocorticoids thought to play a role in Cushing’s?
high cortisol binds and cross-activates mineralocorticoid receptors, resulting in hypokalemia and HTN (Na and fluid retention suppress renin)
How is angiotensin thought to play a role in Cushing’s?
GC stimulate hepatic synth of angiotensinogen, which is converted to ATII
How is vascular reactivity thought to play a role in Cushing’s?
cortisol causes enhanced vascular reactivity to pressors, which results in vasoconstriction and increased peripheral resistance (and increased BP)
What is the relationship between (non-HF) CV risk and natriuretic peptides?
less significant increases in plasma BNP and other natriuretic peptides may indicate an increased risk for CV disease (other than HF)
