What are the clinical indicators for suspecting primary aldosteronism?

Clinical Indicators for Suspecting Primary Aldosteronism

Primary aldosteronism should be suspected in patients with resistant hypertension, hypokalemia (spontaneous or diuretic-induced), hypertension with muscle cramps or weakness, hypertension with incidentally discovered adrenal mass, hypertension with obstructive sleep apnea, or hypertension with family history of early-onset hypertension or stroke. 1

Key Clinical Indicators

Hypertension Patterns

• Resistant hypertension (taking ≥3 antihypertensive drugs including a diuretic with BP above goal, or taking ≥4 drugs including a diuretic with BP at goal) 1
• Abrupt onset of hypertension 1
• Hypertension onset before age 30 1
• Accelerated or malignant hypertension 1
• Abrupt loss of BP control in a previously well-controlled patient 1
• Onset of diastolic hypertension in older adults (≥65 years) 1

Electrolyte Abnormalities

• Hypokalemia (spontaneous or diuretic-induced) 1
• Unprovoked or excessive hypokalemia (when not taking a diuretic) 1
• Muscle cramps or weakness (associated with hypokalemia) 1

Associated Conditions

• Incidentally discovered adrenal mass (adrenal "incidentaloma") 1
• Obstructive sleep apnea 1, 2
• Family history of early-onset hypertension or stroke at young age 1, 2
• Atrial fibrillation (4.2-fold increased risk compared to primary hypertension) 1

Target Organ Damage

• Target organ damage disproportionate to the duration or severity of hypertension 1
• Increased left ventricular hypertrophy and diastolic dysfunction 1
• Increased stiffness of large arteries 1
• Widespread tissue fibrosis 1
• Increased remodeling of resistance vessels 1
• Increased kidney damage compared to primary hypertension matched for BP level 1

Screening Approach

Who to Screen

• Patients with resistant hypertension 1, 3
• Patients with hypokalemia (spontaneous or diuretic-induced) 1, 3
• Patients with adrenal incidentaloma 1, 3
• Patients with family history of early-onset hypertension or stroke 1, 3
• Patients with atrial fibrillation 1, 3
• Patients with obstructive sleep apnea 1, 3

Screening Method

• The aldosterone-to-renin ratio is the most accurate and reliable screening test 1, 2, 3
• A ratio greater than 30 (when plasma aldosterone concentration is reported in ng/dL and plasma renin activity in ng/mL/h) is considered positive 4, 3
• A plasma aldosterone concentration of at least 10-15 ng/dL is required to interpret the test as positive 4, 3

Clinical Significance

Primary aldosteronism is one of the most common causes of secondary hypertension, occurring in:

• 5-10% of all hypertensive patients 1
• 20% of patients with resistant hypertension 1

Early detection is critical as patients with primary aldosteronism have:

• 3.7-fold increased risk of heart failure 1
• 4.2-fold increased risk of stroke 1
• 6.5-fold increased risk of myocardial infarction 1
• 12.1-fold increased risk of atrial fibrillation 1

Common Pitfalls in Diagnosis

• Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value 5
• Medications that can interfere with the aldosterone-renin ratio screening test should be considered:
  • NSAIDs 1
  • Oral contraceptives 1
  • Sympathomimetics 1
  • Mineralocorticoid receptor antagonists (should be withdrawn 4-6 weeks before testing) 1

Treatment Implications

Early diagnosis is important because the deleterious effects of aldosterone excess are often reversible with:

• Unilateral laparoscopic adrenalectomy (for unilateral disease) 1, 5
• Mineralocorticoid receptor antagonists such as spironolactone or eplerenone (for bilateral disease) 1, 5, 6

Delayed diagnosis and treatment may lead to irreversible vascular remodeling and target organ damage, resulting in residual hypertension even after appropriate treatment 5.