Hypoaldosteronism and Hyperaldosteronism: Comprehensive Information

Hyperaldosteronism

Pathophysiology and Clinical Presentation

Primary aldosteronism is characterized by excessive and autonomous aldosterone production from the adrenal glands, independent of the renin-angiotensin system, causing hypertension, sodium retention, renin suppression, and increased potassium excretion. 1

Approximately 50% of cases are unilateral (typically aldosterone-producing adenoma or rarely unilateral hyperplasia), while the remaining 50% are bilateral adrenal hyperplasia (idiopathic hyperaldosteronism) 2, 1
Clinical manifestations include hypertension, weakness, and hypokalemia (though most patients are normokalemic) 2, 3
Excessive aldosterone induces cardiovascular and renal damage beyond simple blood pressure elevation 1

Diagnostic Approach

Screen with the aldosterone-to-renin ratio (ARR), using a cutoff of 30 when plasma aldosterone is in ng/dL and plasma renin activity in ng/mL/h, with plasma aldosterone concentration requiring at least 10 ng/dL for a positive interpretation. 2, 1

Screen hypertensive patients with: resistant hypertension, hypokalemia, adrenal incidentaloma, family history of early-onset hypertension, or stroke at young age (<40 years) 2, 1
Before testing, ensure unrestricted salt intake, normal serum potassium, and withdraw mineralocorticoid receptor antagonists for at least 4 weeks 2
Confirm diagnosis with saline suppression test or oral salt-loading test 2
After confirmation, perform adrenal vein sampling to distinguish unilateral from bilateral aldosterone production, as this determines surgical versus medical management 2
CT imaging alone is insufficient for subtype determination; adrenal vein sampling is the gold standard 2, 3
Consider omitting adrenal vein sampling in patients <40 years with imaging showing only one affected gland, as bilateral hyperplasia is rare in this population 2

Treatment Algorithm

For Unilateral Disease (Adenoma or Unilateral Hyperplasia):

Unilateral laparoscopic adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and achieving complete cure of hypertension in approximately 50% of cases. 2, 1

Surgical removal reverses hypokalemia, lowers blood pressure, reduces antihypertensive medication requirements, and improves cardiac and kidney function parameters 2
For malignant hyperaldosteronism (suspected with irregular morphology, lipid-poor appearance, size >3 cm, or multi-hormone secretion), perform open adrenalectomy due to rupture risk 2
Postoperative monitoring is essential as early diagnosis and treatment improve cure rates; late diagnosis causes vascular remodeling leading to residual hypertension 4

For Bilateral Disease or Non-Surgical Candidates:

Medical management with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment, with spironolactone as first-line therapy. 2, 5

Spironolactone dosing: Start at 12.5-25 mg daily (or 25-50 mg daily per some protocols), titrate up to 100-400 mg daily as needed 5, 6
For primary hyperaldosteronism specifically, FDA-approved dosing is 100-400 mg daily for preoperative preparation or long-term maintenance in non-surgical candidates 5
Eplerenone is an alternative MRA for patients intolerant to spironolactone's side effects (gynecomastia, erectile dysfunction, menstrual irregularities), dosed at 50-100 mg daily 7, 6, 8
Eplerenone is more selective for the mineralocorticoid receptor but less potent than spironolactone 8, 9
If blood pressure remains uncontrolled on MRA monotherapy, add potassium-sparing diuretics (amiloride or triamterene) or calcium channel blockers 6
Both adrenalectomy and medical therapy effectively lower blood pressure and reverse left ventricular hypertrophy 2

Special Considerations:

Glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type-1) can be treated with low-dose dexamethasone 4
Monitor serum electrolytes, creatinine, blood pressure, and fluid status closely when initiating treatment 7, 6
Potassium supplementation may be necessary if hypokalemia persists despite MRA therapy 7
Refer complex or rare cases to specialized hypertension centers 4

Common Pitfalls

Do not rely on CT imaging alone to determine unilateral versus bilateral disease; adrenal vein sampling is required for surgical candidates 2, 3
Do not assume all patients are hypokalemic; most patients with primary aldosteronism are normokalemic 3
Avoid premature discontinuation of MRAs before screening tests, as this causes false-negative results 2
Monitor for hyperkalemia when initiating MRA therapy, especially in patients with reduced kidney function 5

Secondary Hyperaldosteronism

Secondary hyperaldosteronism differs from primary aldosteronism by having elevated both aldosterone AND renin levels (versus suppressed renin in primary aldosteronism), indicating a physiologic response to decreased renal perfusion or volume depletion. 7

Diagnostic Approach

Measure plasma aldosterone concentration and plasma renin activity; both are elevated in secondary hyperaldosteronism 7
Assess serum electrolytes for hypokalemia 7

Treatment

Address the underlying cause (heart failure, cirrhosis, nephrotic syndrome, renal artery stenosis)
Mineralocorticoid receptor antagonists (spironolactone or eplerenone) can be used to manage hypertension and hypokalemia 7
Potassium supplementation may be necessary if hypokalemia persists despite MRA therapy 7
Monitor blood pressure, fluid status, and electrolytes regularly 7