What is the appropriate workup for primary hyperaldosteronism?

Workup for Primary Hyperaldosteronism

The appropriate workup for primary hyperaldosteronism should begin with screening using the aldosterone-to-renin ratio (ARR) in patients with hypertension and hypokalemia, followed by confirmatory testing, and subtype determination through imaging and adrenal venous sampling to guide appropriate treatment. 1, 2

Initial Screening

• Perform a focused history and physical examination to identify signs/symptoms of adrenal hormone excess, particularly hypertension (especially resistant hypertension) and hypokalemia 1
• Screen patients with adrenal incidentalomas and hypertension and/or hypokalemia for primary aldosteronism using an aldosterone-to-renin ratio (ARR) 1
• Ensure patients are potassium-replete before testing, as hypokalemia can suppress aldosterone production 2
• When possible, discontinue medications that interfere with the ARR test, particularly:
  • Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible 2
  • Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR 2
• Collect blood in the morning, with the patient seated for 5-15 minutes immediately before collection 2

Interpreting the Aldosterone-to-Renin Ratio

• An ARR >30 (when aldosterone is measured in ng/dL and renin activity in ng/mL/h) with plasma aldosterone concentration at least 10-15 ng/dL suggests primary aldosteronism 3, 2
• Low renin can artificially elevate the ARR even without truly elevated aldosterone levels, so ensure plasma aldosterone is at least 10 ng/dL for a positive test 3
• The specificity of the ratio improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 3, 2

Confirmatory Testing

• A positive screening test requires confirmation with additional testing 2
• Recommended confirmatory tests include:
  • Intravenous saline suppression test 3
  • Oral sodium loading with 24-hour urine aldosterone measurement 2
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 3, 2
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be withdrawn at least 4 weeks before testing 3, 2

Subtype Determination

• After biochemical confirmation, determine if the condition is unilateral or bilateral 1, 4
• Initial imaging with non-contrast CT scan of the adrenal glands is recommended 1
• Adrenal vein sampling is recommended prior to offering adrenalectomy in patients with primary aldosteronism 1
• Without adrenal vein sampling, up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1, 3

Treatment Options

• For unilateral aldosterone-producing adenomas:
  • Laparoscopic adrenalectomy is the treatment of choice 1, 4
  • Complete biochemical success (normalization of plasma aldosterone, renin, and potassium levels) is achieved in most patients 4
• For bilateral adrenal hyperplasia:
  • Medical management with mineralocorticoid receptor antagonists is recommended 3, 5
  • Spironolactone is the first-line treatment (100-400 mg daily) 5
  • Eplerenone is an alternative when spironolactone side effects occur 3

Common Pitfalls to Avoid

• Not screening high-risk patients is a common pitfall, with only ~2-4% of eligible patients getting screened 2
• Relying solely on hypokalemia as a marker for primary aldosteronism is incorrect, as it is absent in the majority of cases 3, 2
• Interpreting imaging results without adrenal vein sampling can lead to inappropriate treatment decisions 1, 3
• Not considering medication effects on the ARR can lead to false-positive or false-negative results 2

Special Considerations

• There should be a low threshold for multidisciplinary review by endocrinologists, surgeons, and radiologists when:
  • Imaging is not consistent with a benign lesion
  • There is evidence of hormone hypersecretion
  • The tumor has grown significantly during follow-up imaging
  • Adrenal surgery is being considered 1