What are the characteristics of hyperaldosteronism?

Characteristics of Hyperaldosteronism

Primary aldosteronism is characterized by excessive aldosterone production, typically presenting with resistant hypertension, hypokalemia (though often a late manifestation), suppressed plasma renin activity, and metabolic alkalosis. 1

Clinical Presentation

• Hypertension: Often resistant to conventional therapy, with prevalence of 6.1% among general hypertensive patients and up to 20% in patients with resistant hypertension 2
• Hypokalemia: A late manifestation preceded by hypertension, not always present in confirmed cases 2
• Metabolic alkalosis: Due to increased renal hydrogen ion excretion
• Cardiovascular damage: Increased risk of cardiovascular morbidity beyond that expected from blood pressure elevation alone 1
• Renal damage: Progressive renal dysfunction if untreated

Diagnostic Features

Screening

• Aldosterone-to-renin ratio (ARR): First-line screening test with >90% sensitivity when properly performed 1
  • ARR ≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL is considered positive
  • Should be performed in the morning (8-10 AM)
  • Patient should be seated for 5-15 minutes before collection
  • Ensure patient is potassium-replete

High-Risk Groups for Screening

• Resistant hypertension
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Severe hypertension (>180/110 mmHg) - prevalence up to 13% in this group 2
• Hypertension with adrenal incidentaloma
• Early-onset hypertension or family history of early-onset hypertension

Confirmatory Testing

After positive ARR, one of the following confirmatory tests should be performed:

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

Subtypes of Primary Aldosteronism

1. Aldosterone-producing adenoma (APA):

   • Unilateral adrenal adenoma
   • Potentially curable with surgery
   • Accounts for approximately 30-40% of cases

2. Bilateral adrenal hyperplasia (Idiopathic hyperaldosteronism):

   • Bilateral micro or macronodular adrenal hyperplasia
   • Managed medically
   • Accounts for approximately 60-70% of cases

3. Familial hyperaldosteronism (less common):

   • Types 1-4 with specific genetic mutations

Imaging and Localization

• CT or MRI of adrenal glands: Should be performed after biochemical confirmation, not as initial test 1
• Adrenal vein sampling (AVS): Gold standard for distinguishing between unilateral and bilateral aldosterone production
  • Recommended prior to adrenalectomy, particularly in patients >40 years
  • Essential when imaging shows normal-appearing adrenal glands or discordance between biochemical and imaging results

Treatment Options

For Unilateral Disease (APA)

• Laparoscopic adrenalectomy: Treatment of choice 1, 3
  • Improves blood pressure in virtually 100% of patients
  • Achieves complete cure of hypertension in ~50%
  • Preoperative management includes potassium supplementation and blood pressure control

For Bilateral Disease or Non-Surgical Candidates

• Mineralocorticoid receptor antagonists: 1, 3
  • Spironolactone: Initial dose 12.5-25 mg daily, titrated up to 100 mg daily as needed
  • Eplerenone: Alternative with fewer anti-androgenic side effects
  • Monitor for hyperkalemia, especially in patients with reduced renal function

Monitoring and Outcomes

• Regular monitoring of blood pressure, serum potassium, and renal function
• With appropriate treatment, outcomes include:
  • Reduction in blood pressure
  • Normalization of potassium levels
  • Reversal of left ventricular hypertrophy
  • Reduction in cardiovascular and renal complications

Common Pitfalls

• Underdiagnosis: Primary aldosteronism is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups 1
• Reliance on hypokalemia: Serum potassium levels are rarely low in early stages, making hypertension the earlier and more reliable sign 2
• Medication interference: Beta-blockers, NSAIDs, ACE inhibitors, ARBs, and diuretics can affect ARR results and should be considered when interpreting results 1
• Premature imaging: Using CT/MRI before biochemical confirmation can lead to false conclusions, as up to 40% of adrenal incidentalomas are non-functioning 1

Primary aldosteronism requires a systematic approach to diagnosis and treatment to prevent long-term cardiovascular and renal complications. Early recognition and appropriate management significantly improve outcomes and quality of life.