What is the significance of an increased aldosterone:renin ratio in patients with resistant hypertension and no adrenal nodules on computed tomography (CT) scan?

Significance of Elevated Aldosterone:Renin Ratio in Resistant Hypertension with No Adrenal Nodules on CT

An elevated aldosterone:renin ratio (ARR) in resistant hypertension without adrenal nodules on CT strongly suggests primary aldosteronism (PA) due to bilateral adrenal hyperplasia, which requires mineralocorticoid receptor antagonist therapy for optimal blood pressure control and reduction of cardiovascular risk. 1

Diagnostic Significance

• An elevated ARR (≥20-30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h) with plasma aldosterone >15 ng/dL is highly suggestive of primary aldosteronism, even without visible adrenal nodules on CT 2, 1
• Primary aldosteronism is present in 5-10% of all hypertensive patients and up to 20% of patients with resistant hypertension 2, 1
• The absence of adrenal nodules on CT is common in PA and typically suggests bilateral idiopathic hyperplasia rather than an aldosterone-producing adenoma 1

Clinical Implications

• Patients with PA have significantly higher cardiovascular risk compared to those with essential hypertension at the same blood pressure levels:

  • 3.7-fold increase in heart failure
  • 4.2-fold increase in stroke
  • 6.5-fold increase in myocardial infarction
  • 12.1-fold increase in atrial fibrillation
  • Increased left ventricular hypertrophy and diastolic dysfunction 2

• Most patients with PA are normokalaemic, so normal potassium levels should not exclude the diagnosis 3

Confirmation of Diagnosis

After finding an elevated ARR, confirmation of PA requires:

1. Confirmatory testing such as:

   • Oral sodium loading test with 24-hour urine aldosterone measurement
   • IV saline infusion test with plasma aldosterone measurement
   • Fludrocortisone suppression test 1

2. Adrenal vein sampling (AVS) to distinguish between unilateral and bilateral aldosterone production, particularly when:

   • Patient is >40 years old
   • Adrenal glands appear normal on imaging
   • Discordance exists between biochemical and imaging results 1

Treatment Approach

• For bilateral adrenal hyperplasia (most common when no nodules are seen on CT):

  • Mineralocorticoid receptor antagonists (spironolactone 12.5-50 mg/day or eplerenone) are the treatment of choice 1, 3
  • Monitor for hyperkalemia, especially in patients with reduced renal function 1
  • Additional antihypertensive agents may be needed if blood pressure remains uncontrolled 1

• For unilateral disease (if confirmed by AVS despite normal CT):

  • Laparoscopic adrenalectomy is recommended, which improves blood pressure in virtually 100% of patients and may cure hypertension in approximately 50% 1

Important Considerations

• CT has limited sensitivity and specificity for detecting small aldosterone-producing adenomas (<1 cm) 4
• Hypertensive kidney damage can sometimes cause PRA to escape suppression, resulting in a less dramatic elevation of the ARR despite the presence of PA 5
• ARR testing can be performed without discontinuing all antihypertensive medications, though certain drugs (beta-blockers, mineralocorticoid receptor antagonists) may affect results 6
• Long-acting calcium channel blockers and alpha-receptor antagonists have minimal interference with ARR testing 1

Follow-up Recommendations

• Regular monitoring of blood pressure, serum potassium, and renal function
• Titration of medication to achieve target blood pressure
• Careful monitoring for hyperkalemia, especially when initiating therapy or increasing doses of mineralocorticoid receptor antagonists 1

Early diagnosis and appropriate treatment of PA can lead to significant improvement in blood pressure control and reduction in cardiovascular complications, even in patients without visible adrenal adenomas on imaging.