What are the diagnostic criteria for Primary Hyperaldosteronism (PHA)?

From the Guidelines

Diagnosing primary hyperaldosteronism requires a systematic approach, starting with the aldosterone-to-renin ratio (ARR) as the screening test of choice, followed by confirmatory testing and subtype differentiation to guide treatment. The ARR is currently the most accurate and reliable means of screening for primary aldosteronism 1. Initial screening should be performed in patients with hypertension at increased risk of primary aldosteronism, such as those with adrenal incidentaloma, early onset hypertension, and/or cerebrovascular accident at a young age 1.

Key Considerations for Screening

• The ARR requires proper preparation, including discontinuing interfering medications, correcting hypokalemia, and maintaining a normal sodium diet 1.
• A positive ARR (typically >30 ng/dL per ng/mL/hr with aldosterone >10 ng/dL) should be followed by confirmatory testing such as the intravenous saline suppression test or oral salt-loading test 1.
• Patients should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antagonists withdrawn for at least 4 weeks before testing 1.

Confirmatory Testing and Subtype Differentiation

• Once primary aldosteronism is confirmed, subtype differentiation is necessary through adrenal imaging (CT or MRI) to identify adenomas, and adrenal vein sampling to determine if aldosterone production is unilateral or bilateral 1.
• This differentiation is crucial as unilateral disease (typically aldosterone-producing adenoma) is treated surgically, while bilateral disease (idiopathic hyperaldosteronism) is managed medically with mineralocorticoid receptor antagonists like spironolactone or eplerenone 1.
• For unilateral primary aldosteronism, surgical removal of the offending adrenal gland is typically considered, unless the patient is older or has co-morbidities of concern 1.
• Medical treatment is currently based on MRAs, with spironolactone being the most widely available, and eplerenone being an alternative option with less gynaecomastia and erectile dysfunction in men 1.

From the Research

Diagnosis of Primary Hyperaldosteronism

To diagnose primary hyperaldosteronism, the following steps can be taken:

• Screening for primary aldosteronism is typically done by determining the plasma aldosterone to renin ratio (ARR) 2, 3, 4, 5
• If the screening test is positive, confirmatory testing is necessary to establish the diagnosis 2, 3, 5
• Common confirmatory tests include:
  • Oral sodium loading
  • Intravenous saline infusion
  • Captopril challenge
  • Fludrocortisone administration plus sodium loading 5
• Once the diagnosis is confirmed, imaging and adrenal venous sampling (AVS) are used to determine the subtype and lateralization of aldosterone production 2, 3, 5
• Unilateral hyperaldosteronism is typically treated with laparoscopic adrenalectomy, while bilateral hyperaldosteronism is treated with low-dose mineralocorticoid receptor antagonists (MRAs) and other medications as needed 2

Test Characteristics

The test characteristics of the aldosterone-renin ratio as a screening test for primary aldosteronism are not well established, with varying cutoff values and limited data on sensitivity and specificity 4

• A systematic review of the literature found that none of the studies provided valid estimates of the test characteristics of the aldosterone-renin ratio 4
• Further research is needed to establish the optimal cutoff values and test characteristics for the aldosterone-renin ratio as a screening test for primary aldosteronism 2, 4

Clinical Approach

A clinical approach to diagnosing primary aldosteronism involves:

• Screening at-risk populations, such as those with hypertension 2, 3, 6
• Confirmatory testing for positively screened patients 2, 3, 5
• Subtype classification to direct surgical or medical management 3
• Treatment objectives to reduce the risk of incident cardiovascular disease 6