What is the diagnosis and treatment for hypertension secondary to hyperaldosteronism (Primary Aldosteronism)?

From the Guidelines

For patients with hypertension secondary to hyperaldosteronism, the most effective treatment approach is to use mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone, as they directly block the effects of aldosterone, according to the most recent guidelines 1.

Treatment Approach

The management of hypertension secondary to hyperaldosteronism involves addressing the underlying cause of the condition while controlling blood pressure.

• First-line medications include MRAs like spironolactone (25-100 mg daily) or eplerenone (25-50 mg daily), which are particularly effective in blocking aldosterone's effects.
• Angiotensin-converting enzyme (ACE) inhibitors like lisinopril (10-40 mg daily) or angiotensin II receptor blockers (ARBs) such as losartan (25-100 mg daily) can also be used to reduce aldosterone production.
• Diuretics such as hydrochlorothiazide (12.5-25 mg daily) may be added to enhance blood pressure control.

Diagnosis and Screening

• The aldosterone:renin activity ratio is the most accurate and reliable means of screening for primary aldosteronism, with a cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h) 1.
• Patients with hypertension and a history of early onset hypertension and/or cerebrovascular accident at a young age may have primary aldosteronism due to glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type-1) and therefore warrant screening.

Lifestyle Modifications

• Lifestyle modifications are essential, including sodium restriction (<2.3 g/day), weight management, regular exercise, and limiting alcohol consumption.
• Potassium levels should be monitored regularly, especially when using potassium-sparing diuretics or ACE inhibitors/ARBs, as hyperkalemia is a risk. The effectiveness of this approach stems from interrupting the pathophysiological cascade that leads to sodium retention, potassium excretion, and volume expansion, which are the mechanisms by which aldosterone elevates blood pressure, as supported by recent guidelines 1.

From the FDA Drug Label

2.5 Treatment of Primary Hyperaldosteronism Administer spironolactone tablets in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Treatment of Hypertension Secondary to Hyperaldosteronism: The recommended dose of spironolactone for the treatment of hypertension secondary to hyperaldosteronism is 100 mg to 400 mg daily.

• The dosage can be adjusted based on the individual patient's response to the medication.
• Spironolactone can be used as long-term maintenance therapy for patients who are not candidates for surgery 2. Key Considerations:
• Monitor patients for signs of hyperkalemia, as spironolactone can increase serum potassium levels.
• Adjust the dosage accordingly to minimize the risk of hyperkalemia 2.

From the Research

Hypertension Secondary to Hyperaldosteronism

• Hypertension secondary to hyperaldosteronism is a significant health concern, with primary hyperaldosteronism being the most common form of secondary hypertension 3.
• The condition has a strong correlation with cardiovascular disease, and failure to recognize and properly diagnose it can have profound health consequences 3.
• The diagnostic pursuit for primary hyperaldosteronism is complex, and new concepts have emerged in all areas of this clinical condition, including identification, diagnosis, and treatment 3.

Treatment Options

• Aldosterone antagonists, such as spironolactone, are the mainstay of therapy in patients with hypertension due to primary aldosteronism 4, 5.
• However, angiotensin-converting enzyme (ACE) inhibitors are not recommended for patients with primary aldosteronism, as they are unlikely to lower blood pressure in patients with low renin levels 5.
• Eplerenone, a selective aldosterone antagonist, is a viable alternative to spironolactone, with fewer adverse effects due to its selectivity for the mineralocorticoid receptor (MR) 4, 6, 7.
• New agents, such as non-steroidal MR antagonists and aldosterone synthase inhibitors, are being developed to provide more effective treatment options for hyperaldosteronism 7.

Clinical Implications

• The use of aldosterone antagonists has been expanded to include congestive heart failure and first-line treatment of mild-to-moderate hypertension 6.
• The addition of spironolactone to an ACE inhibitor has been shown to cause marked diuresis and symptomatic improvement in patients with congestive heart failure 4.
• The RALES study demonstrated a 30% decrease in mortality and hospitalization for cardiac causes in spironolactone-treated patients compared to the placebo group 4.