What is the approach to diagnosing hyperaldosteronism (primary aldosteronism)?

From the Guidelines

The approach to diagnosing hyperaldosteronism (primary aldosteronism) should begin with screening tests, specifically measuring the aldosterone-to-renin ratio (ARR), in patients with suspicious clinical features, and confirmation with suppression testing is required for a definitive diagnosis. The most recent and highest quality study, 1, published in 2024, provides guidance on the management of primary aldosteronism. According to this study, primary aldosteronism is the most common form of secondary hypertension, and its management depends on its subtype, particularly on adrenal lesions being unilateral or bilateral.

Screening and Diagnosis

The initial screening involves measuring the ARR while the patient is on an unrestricted salt diet and after correcting hypokalemia. Most antihypertensive medications should be discontinued 2 weeks before testing, except for verapamil, hydralazine, or alpha-blockers which minimally affect results. A positive ARR (typically >20-30 ng/dL per ng/mL/hr) requires confirmation with suppression testing, such as the saline infusion test (2L normal saline over 4 hours) or oral salt loading test.

Imaging and Adrenal Vein Sampling

Once autonomous aldosterone production is confirmed, imaging with adrenal CT or MRI should be performed to identify potential adenomas. To determine if hyperaldosteronism is unilateral (typically adenoma) or bilateral (typically hyperplasia), adrenal vein sampling is the gold standard, particularly in patients being considered for surgery. This procedure measures aldosterone and cortisol from both adrenal veins to calculate lateralization ratios.

Treatment

Unilateral disease is typically treated surgically with adrenalectomy, while bilateral disease is managed medically with mineralocorticoid receptor antagonists like spironolactone (25-100 mg daily) or eplerenone (50-100 mg daily) 1. The effective dose of spironolactone can be titrated up to 300–400 mg once daily, if necessary. Eplerenone is also used and, despite being less potent than spironolactone and requiring twice-daily administration, it has the advantage of causing less gynaecomastia and erectile dysfunction in men.

Key Considerations

The management of primary aldosteronism depends on its subtype, and adrenal vein sampling is essential to determine the lateralization of aldosterone production. Medical treatment with mineralocorticoid receptor antagonists is effective in lowering blood pressure and reversing left ventricular hypertrophy (LVH) in patients with bilateral disease or those who are not candidates for surgery 1.

From the FDA Drug Label

1. 4 Primary Hyperaldosteronism Spironolactone tablets are indicated in the following settings: Short-term preoperative treatment of patients with primary hyperaldosteronism. Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).
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.

The approach to diagnosing hyperaldosteronism (primary aldosteronism) is not directly addressed in the provided drug labels. However, the labels do provide information on the treatment of primary hyperaldosteronism using spironolactone tablets.

• Diagnosis is not mentioned, but treatment options are discussed, including short-term preoperative treatment and long-term maintenance therapy.
• The labels do not provide a clear diagnostic approach, but rather focus on the treatment of the condition once diagnosed.
• It is essential to consult other medical resources or guidelines for the diagnosis of primary hyperaldosteronism, as the provided drug labels do not provide sufficient information on this topic 2, 2, 2.

From the Research

Approach to Diagnosing Hyperaldosteronism (Primary Aldosteronism)

The approach to diagnosing hyperaldosteronism (primary aldosteronism) involves a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management 3, 4.

• The aldosterone-to-renin ratio is the most sensitive screening test for primary aldosteronism 3.
• Confirmatory tests include the furosemide test, and the current literature does not identify a "gold standard" confirmatory test for primary aldosteronism 3.
• After case confirmation, all patients with primary aldosteronism should undergo adrenal CT as the initial study in subtype testing to exclude adrenocortical carcinoma 3.
• Bilateral adrenal vein sampling (AVS) is the gold standard method to define the primary aldosteronism subtype, but it is not indicated in all cases 3, 4.
• An experienced radiologist must perform AVS 3.

Subtype Differentiation and Treatment

Subtype differentiation is crucial for therapeutic management, as unilateral and bilateral forms of primary aldosteronism require different treatment approaches 3, 4.

• Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with aldosterone-producing adenomas (APAs) 3, 4.
• Bilateral hyperplasia should be treated with mineralocorticoid antagonists (spironolactone or eplerenone) 3, 4.
• Cardiovascular morbidity caused by aldosterone excess can be decreased by either unilateral adrenalectomy or mineralocorticoid antagonist 3, 5.

Goals of Treatment

The goals of treatment are to normalize both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality 4.

• Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent 4.
• Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia 4.
• Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients 4.