What are the diagnostic criteria for primary hyperaldosteronism (Conn's syndrome)?

From the Guidelines

Hyperaldosteronism is diagnosed through a stepwise approach beginning with screening tests in patients with suspicious clinical features such as resistant hypertension, hypokalemia, or adrenal incidentaloma, with the initial screening test being the aldosterone-to-renin ratio (ARR) measured in the morning after the patient has been upright for at least 2 hours, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. The diagnostic approach for hyperaldosteronism involves several key steps:

• The initial screening test is the aldosterone-to-renin ratio (ARR), which should be measured in the morning after the patient has been upright for at least 2 hours, with an ARR greater than 30 ng/dL per ng/mL/hr suggesting hyperaldosteronism 1.
• Before testing, interfering medications such as spironolactone and eplerenone should be discontinued for at least 4 weeks, and 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should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antagonists withdrawn for at least 4 weeks before testing 1.
• If the ARR is elevated, confirmatory testing is required using one of several methods: oral sodium loading test, saline infusion test, captopril challenge test, or fludrocortisone suppression test, to assess whether aldosterone secretion is appropriately suppressed under conditions that should normally reduce it 1.
• Once biochemical confirmation is obtained, imaging studies (CT or MRI of the adrenal glands) and adrenal vein sampling are performed to distinguish between bilateral adrenal hyperplasia and aldosterone-producing adenoma, as this distinction determines whether medical management or surgical intervention is appropriate 1. This diagnostic approach is essential because correctly identifying the subtype of hyperaldosteronism guides treatment decisions and can potentially cure hypertension in patients with aldosterone-producing adenomas, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. Key considerations in the diagnosis of hyperaldosteronism include:
• The aldosterone:renin activity ratio is currently 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.
• The plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive, due to the potential influence of very low renin levels on the aldosterone:renin activity ratio 1.
• Patients with primary aldosteronism have a higher risk of cardiovascular and kidney damage, and treatment with mineralocorticoid receptor antagonists or unilateral adrenalectomy can improve blood pressure and reduce the risk of these complications, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

From the Research

Diagnosis of Hyperaldosteronism

• The diagnosis of primary aldosteronism (PA) involves a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management 2, 3, 4, 5.
• Screening for PA is typically done by determining the plasma aldosterone to renin ratio (ARR), followed by one of several confirmatory/exclusion tests such as oral salt loading, saline infusion, captopril challenge, and fludrocortisone suppression test 2, 3, 4.
• Confirmatory tests are necessary to avoid false positives and to determine the subtype of PA, as the treatment differs for each subtype 2, 3, 4, 5.
• Adrenal venous sampling (AVS) is a key test for reliable subtype identification, but can be bypassed in patients with specific characteristics 3, 5.
• Imaging studies, such as computerized axial tomography (CT) of the adrenal glands, are also used to localize the source of aldosterone excess 4, 5.

Diagnostic Tests

• Aldosterone-to-renin ratio (ARR) is the most practical and informative initial test for screening PA 2, 3, 4.
• Oral salt loading, saline infusion, captopril challenge, and fludrocortisone suppression test are commonly used confirmatory tests 2, 3, 4.
• Intravenous saline infusion test or captopril test are also used as confirmatory tests 4.
• Adrenal venous sampling (AVS) is the definitive localization test in most cases 3, 4, 5.

Importance of Diagnosis

• Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities 5, 6.
• Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies can mitigate aldosterone-specific target organ damage and improve patient outcomes 5, 6.
• Recognition and treatment of primary aldosteronism require a multidisciplinary approach with primary care physicians, cardiologists, endocrinologists, and radiologists working collaboratively 6.