A 55-year-old man comes to the office for follow-up of hypertension. The diagnosis was made 3 months ago after the patient experienced a transient ischemic attack. He has occasional headaches and general fatigue but otherwise feels well. Current medications include aspirin, lisinopril, and low-dose chlorthalidone. Blood pressure is 157/95 mm Hg and pulse is 69/min. BMI is 26 kg/m2. Cardiac auscultation reveals an S4 heart sound. There are no carotid or abdominal bruits on examination. Pulses are 2+ in all extremities. Laboratory results are as follows:
| Potassium | 3.1 mEq/L |
| Creatinine | 0.9 mg/dL |
| Plasma renin activity | low |
Which of the following best explains this patient's laboratory findings?
Adrenocortical causes of hypertension | ||||
Plasma aldosterone | Plasma renin activity | Aldosterone/ | Clinical examples | |
Primary hyperaldosteronism | ↑ | ↓ | ↑ |
|
Secondary hyperaldosteronism | ↑ | ↑ | ↔ |
|
Nonaldosterone mediated | ↓ | ↓ | ↔ |
|
*Includes deoxycorticosterone-producing adrenal tumors (rare) & relatively uncommon forms of HTN = hypertension. | ||||
This patient with low plasma renin likely has secondary hypertension due to primary hyperaldosteronism, which is typically caused by an adrenal adenoma or bilateral adrenal hyperplasia. Primary hyperaldosteronism is characterized by autonomous aldosterone secretion that leads to increased intravascular volume and hypertension. Hypertension can cause headaches if severe and left ventricular hypertrophy (eg, S4 heart sound) if prolonged.
The elevated serum aldosterone causes suppressed plasma renin activity (PRA) due to feedback inhibition of the renin-angiotensin-aldosterone system. Electrolyte abnormalities such as hypokalemia and metabolic alkalosis are often present due to aldosterone-mediated K+ and H+ secretion, respectively. The addition of a thiazide diuretic (eg, chlorthalidone) for treatment of hypertension can substantially worsen these electrolyte abnormalities (as in this patient).
Despite increased Na+ reabsorption, extravascular volume overload (eg, peripheral edema) is rarely seen due to aldosterone escape.
(Choice A) Thiazides (eg, chlorthalidone) inhibit the Na+-Cl− cotransporter in the distal convoluted tubule, which results in natriuresis and potassium wasting. Although thiazide use explains this patient's hypokalemia (which can cause fatigue), by itself it would be expected to cause a rise in PRA due to reduced intravascular volume and decreased Na+ delivery to the macula densa (which stimulates renin release).
(Choice B) ACE inhibitors (eg, lisinopril) decrease conversion of angiotensin I to angiotensin II, which results in a compensatory rise in PRA in addition to reduced glomerular filtration rate due to efferent arteriole vasodilation. A mild rise in serum creatinine and an increase in serum potassium are often seen.
(Choice C) Malignant hypertension is characterized by markedly elevated blood pressure with end-organ damage to the eye (eg, retinal hemorrhages, papilledema), CNS (eg, hemorrhage, encephalopathy), and kidneys (eg, nephrosclerosis). Kidney involvement results in creatinine elevation (normal in this patient) and dysregulated renin release that leads to a paradoxically high PRA.
(Choice E) Renovascular hypertension is characterized by decreased renal perfusion (most often due to unilateral renal artery stenosis) that results in an inappropriately high PRA that leads to hypertension. An abdominal bruit is typically auscultated.
Educational objective:
Primary hyperaldosteronism results in hypertension and predisposes to electrolyte abnormalities (ie, hypokalemia, metabolic alkalosis). Low plasma renin activity is expected.