What are the diagnostic criteria for Conn's syndrome?

Diagnostic Criteria for Conn's Syndrome (Primary Aldosteronism)

The diagnosis of Conn's syndrome requires demonstrating autonomous aldosterone overproduction through biochemical testing, followed by imaging and potentially adrenal vein sampling to determine if the source is unilateral or bilateral. 1

Initial Biochemical Evaluation

• Screening Tests:

  • Elevated aldosterone-renin ratio (ARR) - the primary screening test
  • Documented hypokalemia (if present)
  • Inappropriate kaliuresis despite hypokalemia
  • Metabolic alkalosis 1, 2

• Confirmatory Tests:

  • Saline suppression test - failure to suppress aldosterone production with saline infusion 3
  • Other options include fludrocortisone suppression test, captopril challenge test, or oral sodium loading test

Clinical Features Supporting Diagnosis

• Hypertension (often resistant to conventional therapy)
• Hypokalemia (present in most but not all cases)
• Weakness, fatigue, muscle cramps, palpitations related to hypokalemia
• Polyuria and polydipsia 4
• Metabolic alkalosis 2

Imaging Studies

• Adrenal CT scan or MRI to identify potential adenomas
  • Sensitivity is limited for small adenomas (<1 cm)
  • Cannot reliably distinguish between functioning and non-functioning adenomas 1

Adrenal Vein Sampling

• Gold standard for distinguishing unilateral from bilateral disease
• Essential for treatment planning in most cases
• May be omitted in patients <40 years with clear unilateral adrenal adenoma on imaging 1
• Lateralization is determined by comparing aldosterone/cortisol ratios between the two adrenal veins

Diagnostic Algorithm

1. Screening Phase:

   • Measure plasma aldosterone concentration (PAC) and plasma renin activity (PRA)
   • Calculate aldosterone-renin ratio (ARR)
   • Document hypokalemia and inappropriate kaliuresis (if present)
   • Check for metabolic alkalosis

2. Confirmatory Phase:

   • Perform saline suppression test or alternative confirmatory test
   • Failure to suppress aldosterone confirms autonomous production

3. Subtype Determination:

   • Adrenal imaging (CT or MRI) to identify potential adenomas
   • Adrenal vein sampling to distinguish unilateral from bilateral disease
   • Lateralization index >4 suggests unilateral disease

Common Pitfalls and Caveats

• Medication Interference:

  • Antihypertensives (especially spironolactone, eplerenone) should be discontinued 4-6 weeks before testing
  • Beta-blockers, ACE inhibitors, and ARBs can affect renin levels
  • Diuretics can cause false positives through volume depletion

• Hypokalemia Correction:

  • Severe hypokalemia should be corrected before testing as it can suppress aldosterone production

• Posture Effects:

  • Aldosterone and renin measurements are affected by posture; standardized collection protocols are essential

• Adrenal Incidentalomas:

  • Not all adrenal masses are functioning adenomas; biochemical confirmation is essential before attributing symptoms to an incidentally discovered adrenal mass 5

Treatment Implications of Diagnosis

• Unilateral disease (typically adenoma): Laparoscopic adrenalectomy is the treatment of choice
• Bilateral disease (typically hyperplasia): Medical management with mineralocorticoid receptor antagonists 1
• After successful treatment, expect normalization of potassium levels in virtually all patients and resolution or improvement of hypertension in most patients 6

The diagnostic approach should be systematic and thorough, as accurate diagnosis and subtype determination are critical for selecting the appropriate treatment strategy that will optimize outcomes related to morbidity, mortality, and quality of life.