What are the diagnostic criteria and treatment options for Conn's syndrome?

Diagnosing Conn's Syndrome (Primary Aldosteronism)

The diagnosis of Conn's syndrome requires measurement of the aldosterone-to-renin ratio (ARR) as the initial screening test, followed by confirmatory testing and adrenal imaging to differentiate between unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia. 1, 2

Diagnostic Approach

Initial Screening

• Measure aldosterone-to-renin ratio (ARR) as the first screening test for primary aldosteronism 2, 3
• Optimal ARR testing conditions include:
  • Patient at rest
  • Adjusted blood pressure medication (when possible)
  • Corrected potassium balance 3
• Minimum criteria for positive screening: plasma aldosterone concentration ≥10 ng/dL and plasma renin activity ≥0.5 ng/mL/h 2

Clinical Presentation

• Hypertension (often resistant to conventional therapy requiring multiple medications) 3, 4
• Hypokalemia (may present with weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria) 4
• Metabolic alkalosis 5
• Normal or elevated sodium levels 3

Confirmatory Testing

• Saline infusion suppression test or oral salt loading test 2
• Fludrocortisone suppression test in cases with unclear diagnosis 6

Imaging and Localization

• CT scan of adrenal glands to identify adenoma 3, 5
• Selective adrenal vein sampling (current gold standard) to differentiate between unilateral and bilateral disease 1, 3
• Functional imaging with radiolabeled tracers may be used as an alternative to adrenal vein sampling in some cases 1

Treatment Options

For Unilateral Disease (Conn's Syndrome)

• Laparoscopic adrenalectomy of the affected adrenal gland is the treatment of choice 1, 3, 7
• Expected outcomes after successful surgery:
  • Normalization of potassium levels in nearly 100% of cases 7, 5
  • Resolution of hypertension in 50-90% of patients 7, 5
  • Residual hypertension may persist in approximately 45% of patients, especially those with long-standing hypertension 5

For Bilateral Disease or Contraindications to Surgery

• Mineralocorticoid receptor antagonists (MRAs) are the cornerstone of medical therapy 1, 4
• Spironolactone is the most widely used MRA:
  • Starting dose: 50-100 mg once daily
  • Can be titrated up to 300-400 mg once daily if necessary 1
• Eplerenone is an alternative with fewer side effects (less gynaecomastia and erectile dysfunction):
  • Requires twice-daily administration
  • Less potent than spironolactone 1
• Newer agents under investigation:
  • Non-steroidal MRAs (finerenone and exarenone)
  • Aldosterone synthase inhibitor (baxdrostat) 1

Common Pitfalls and Caveats

• Conn's syndrome is the most common form of secondary hypertension but remains underdiagnosed 3
• Medications that can interfere with ARR testing include:
  • Beta-blockers (may suppress renin)
  • ACE inhibitors and ARBs (may increase renin)
  • Diuretics (may affect both aldosterone and renin) 3
• Bilateral renal artery stenosis can coexist with Conn's syndrome and complicate the diagnostic picture 6
• In patients with kidney transplantation, diagnosis can be challenging due to high prevalence of hypertension (70-90%) and common electrolyte abnormalities in this population 4
• Even with negative screening tests, consider adrenal vein sampling in patients with resistant hypertension and unexplained hypokalemia 6

By following this diagnostic approach and treatment algorithm, clinicians can effectively identify and manage patients with Conn's syndrome, leading to improved blood pressure control and correction of metabolic abnormalities.