What is the initial evaluation for diagnosing hyperaldosteronism vs other adrenal masses?

Diagnosis of Hyperaldosteronism vs Other Adrenal Masses

For diagnosing hyperaldosteronism versus other adrenal masses, the aldosterone-to-renin ratio (ARR) is the preferred initial test in patients with hypertension and/or hypokalemia, with a value ≥20 ng/dL per ng/mL/hr having excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism. 1

Initial Evaluation for Hyperaldosteronism

Clinical Indicators to Suspect Hyperaldosteronism

• Hypertension with hypokalemia (spontaneous or diuretic-induced)
• Resistant hypertension
• Early-onset hypertension or family history of early-onset hypertension
• Symptoms such as muscle cramping, weakness, headaches, or intermittent paralysis 2

Laboratory Testing

1. Aldosterone-to-Renin Ratio (ARR):

   • Must be performed under specific conditions:
     • Morning collection (after patient has been out of bed for 2 hours)
     • Patient seated for 5-15 minutes before collection
     • Patient should be potassium-replete
     • Interfering medications should be discontinued when possible 1
   • Interpretation:
     • ARR ≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL is considered positive 1, 2
     • Some centers use higher cutoffs (≥30) for increased specificity 2

2. Confirmatory Testing (if ARR is positive):

   • Intravenous saline suppression test
   • Oral salt-loading test with 24-hour urine aldosterone measurement
   • Fludrocortisone suppression test 1, 2

Imaging

• Non-contrast CT scan of adrenal glands (or MRI if CT is contraindicated) after biochemical confirmation 2
• Imaging helps identify adrenal nodules but cannot reliably distinguish between functional and non-functional masses 1

Adrenal Vein Sampling

• Gold standard for distinguishing between unilateral and bilateral aldosterone production
• Essential before considering adrenalectomy, particularly in:
  • Patients >40 years old
  • Normal-appearing adrenal glands on imaging
  • Discordance between biochemical and imaging results 2

Differential Diagnosis of Adrenal Masses

1. Cortisol-Secreting Lesions

• Screening Test: 1 mg overnight dexamethasone suppression test (DST) for all adrenal incidentalomas 1
• Interpretation:
  • <50 nmol/L excludes cortisol hypersecretion
  • 51-138 nmol/L suggests possible autonomous cortisol secretion

  • 138 nmol/L indicates cortisol hypersecretion 1

• Additional Testing: Plasma ACTH, 24-hr urinary-free cortisol, midnight salivary cortisol 1

2. Pheochromocytoma

• Indications for Testing:
  • Adrenal incidentalomas with ≥10 HU on non-contrast CT
  • Signs/symptoms of catecholamine excess (headaches, anxiety attacks, sweating, palpitations) 1
• Screening Test: Plasma free metanephrines or 24-hour urinary metanephrines 1
• Interpretation: >2× upper limit of normal is diagnostic 1

3. Adrenocortical Carcinoma

• Indications for Testing:
  • Suspected ACC
  • Clinical signs of virilization 1
• Testing: DHEAS, testosterone, and other androgens 1
• Additional Testing: 17b-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1

Management Considerations

For Hyperaldosteronism

• Unilateral Disease: Laparoscopic adrenalectomy is treatment of choice

  • Improves BP in virtually 100% of patients
  • Complete cure of hypertension in ~50% 1, 2

• Bilateral Disease or Non-surgical Candidates: Medical therapy with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 1, 2

Important Pitfalls to Avoid

1. Medication Interference with ARR Testing:

   • Discontinue beta-blockers, centrally acting drugs, diuretics, and mineralocorticoid receptor antagonists when feasible
   • Long-acting calcium channel blockers and alpha-receptor antagonists have minimal interference and can be continued 2

2. Interpretation Challenges:

   • Very low renin levels can falsely elevate ARR
   • Plasma aldosterone should be at least 10 ng/dL for a positive test 1
   • Consider menstrual cycle timing in females when interpreting ARR 2

3. Diagnostic Accuracy:

   • Clinical and laboratory data alone cannot reliably differentiate between adenoma and bilateral hyperplasia due to overlap in presentation 3
   • Imaging and adrenal vein sampling are essential for accurate diagnosis 2

By following this systematic approach to evaluating adrenal masses, hyperaldosteronism can be accurately diagnosed and distinguished from other adrenal pathologies, leading to appropriate treatment decisions and improved patient outcomes.