What is the initial treatment for hyperaldosteronism?

Initial Treatment for Hyperaldosteronism

The initial treatment for hyperaldosteronism depends critically on whether it is primary (autonomous adrenal production) or secondary (elevated renin-driven), and if primary, whether it is unilateral or bilateral disease. 1, 2

Distinguishing Primary vs Secondary Hyperaldosteronism

• Measure plasma aldosterone concentration and plasma renin activity simultaneously to differentiate between primary and secondary hyperaldosteronism 1
• In secondary hyperaldosteronism, both aldosterone and renin are elevated, whereas in primary hyperaldosteronism, renin is suppressed 1
• The underlying cause of secondary hyperaldosteronism (heart failure, cirrhosis, nephrotic syndrome) should guide treatment of the primary condition 3

Primary Hyperaldosteronism: Subtype Determines Treatment

For Unilateral Disease (Adenoma or Unilateral Hyperplasia):

• Laparoscopic unilateral adrenalectomy is the definitive treatment of choice for unilateral primary hyperaldosteronism 2
• Surgery improves blood pressure in virtually 100% of patients and achieves complete cure of hypertension in approximately 50% of cases 2
• Adrenal vein sampling is the gold standard for distinguishing unilateral from bilateral disease before proceeding to surgery 2

For Bilateral Disease (Idiopathic Hyperaldosteronism):

• Spironolactone is the first-line medical treatment, initiated at 50-100 mg/day and titrated up to a maximum of 300-400 mg/day as needed 2, 4, 5
• The FDA-approved dosing for primary hyperaldosteronism is 100-400 mg daily in preparation for surgery or as long-term maintenance therapy 4
• Eplerenone (50-100 mg/day initially, up to 200 mg/day) can be used as an alternative in patients who cannot tolerate spironolactone's side effects, particularly gynecomastia 1, 6
• Eplerenone is equally effective as spironolactone for blood pressure control in bilateral disease, with similar rates of mild hyperkalemia but without anti-androgenic effects 6

Practical Treatment Algorithm

Step 1: Initiate Mineralocorticoid Receptor Antagonist

• Start spironolactone 25-50 mg once daily (lower starting dose of 12.5-25 mg can be used) 5
• Alternatively, start eplerenone 25 mg twice daily if anti-androgenic side effects are a concern 6
• Administer for at least 5 days before increasing dose to assess response 4

Step 2: Titrate Based on Response

• Increase spironolactone gradually up to 100 mg/day, then to 200-400 mg/day if blood pressure remains uncontrolled 2, 4, 5
• For eplerenone, titrate up to 200 mg/day maximum 6
• Monitor serum potassium and creatinine closely at initiation and with each dose adjustment 1, 5

Step 3: Add Additional Agents if Needed

• If blood pressure is not normalized with mineralocorticoid receptor antagonist monotherapy, add potassium-sparing diuretics (amiloride or triamterene) or calcium channel blockers 5
• Hydrochlorothiazide 12.5 mg daily can be added for resistant cases 6

Critical Monitoring Parameters

• Check serum potassium, sodium, and creatinine regularly to assess treatment response and detect complications 1, 5
• Monitor blood pressure and fluid status at each visit 1
• Reduce or discontinue spironolactone if hyperkalemia develops (particularly in patients with renal impairment) 4, 7
• Potassium supplementation may be necessary if hypokalemia persists despite treatment 1

Important Caveats

• Patients with severe hypertension and renal damage may have inappropriately elevated renin despite primary hyperaldosteronism, making diagnosis more challenging 7
• These patients may respond to spironolactone with marked increases in serum creatinine and potassium, requiring cautious dosing 7
• Early diagnosis and treatment are crucial to prevent irreversible vascular remodeling that can cause persistent hypertension even after successful treatment 2
• Side effects of spironolactone include hyperkalemia, gynecomastia, breast tenderness, decreased libido, and erectile dysfunction 3, 4
• In patients with cirrhosis and secondary hyperaldosteronism, initiate therapy in a hospital setting with slow titration due to high risk of complications 4