Epidemiology

Etiology

Most commonly due to the following conditions:
- Bilateral idiopathic hyperplasia of the adrenal glands (∼ 60%)
- Aldosterone-producing adrenal adenoma or aldosteronoma (∼ 30%)

Physiological aldosterone secretion is regulated by the renin-angiotensin-aldosterone system (RAAS) and occurs in response to the detection of low blood pressure in the kidneys (see “Renin-angiotensin-aldosterone system”).
↑ Aldosterone → ↑ open Na⁺ channels in principal cells of luminal membrane at the cortical collecting ducts of the kidneys → ↑ Na⁺ reabsorption and retention → water retention → hypertension
Aldosterone escape
- Definition: Evasion of the Na⁺-retaining effects of inappropriately elevated aldosterone levels in primary hyperaldosteronism
- Mechanism: sodium and water retention → volume expansion → secretion of atrial natriuretic peptide (ANP) and pressure natriuresis → compensatory diuresis → “escape” from edema formation and hypernatremia

↑ Na⁺ reabsorption → electronegative lumen → electrical gradient through open K⁺ channels → ↑ K⁺ secretion → hypokalemia
Hypokalemia → metabolic alkalosis via two mechanisms (both of which decrease extracellular H⁺, thereby increasing extracellular pH):
- Efflux of K⁺ from intracellular to extracellular space in exchange for H⁺
- ↑ H⁺ secretion in the kidney in order to enable ↑ K⁺ reabsorption
Diabetes insipidus: hypokalemia → desensitization of renal tubules to antidiuretic hormone (ADH) → polyuria and polydipsia

Tip

Primary hyperaldosteronism is characterized by hypokalemia and drug-resistant hypertension.

Etiology
- Renal artery stenosis (e.g., due to atherosclerosis, fibromuscular dysplasia)
- Renin-secreting tumor
- Chronic kidney disease
- Advanced CHF
- Fibromuscular dysplasia
- Liver cirrhosis
- Diuretics
- Laxative abuse
Diagnostics: ↑ PAC (Plasma aldosterone concentration) and ↑ PRA (Plasma renin activity)

Unilateral disease or adrenal carcinoma: surgery preferred
Bilateral disease: medical management preferred
- Bilateral adrenalectomy has a low success rate for curing hypertension and also leaves the patient dependent on lifelong glucocorticoid replacement; for this reason, medical management is recommended for bilateral disease.

First-line: aldosterone receptor antagonists
- Spironolactone (preferred)
- Eplerenone
  - In contrast to spironolactone, eplerenone does not block androgen or progesterone receptors, which decreases certain side effects (e.g., gynecomastia and decreased libido); however, eplerenone is only half as potent at blocking the mineralocorticoid receptor and is less effective at lowering blood pressure.