Aldosteronism

Key Points

Measuring Aldosterone-to-Renin Ratio (ARR)

Suggested approach from the Endocrine Society (Funder, 2016)

• Interpreting ARR test results
  • Positive or equivocal – requires confirmation
  • Negative – primary aldosteronism unlikely
  • Factors that may lead to false-positive or false-negative ARR results (Funder, Endocrine Society Guideline, 2016)

    Factors That May Lead to False-positive or False-negative ARR Results*
    Factor	Effect on aldosterone plasma levels	Effect on renin levels	Effect on ARR
    Medications**
    ACE inhibitors	↓	↑ ↑	↓ (false negative)
    Angiotensin II type 1 receptor blockers
    Potassium-sparing diuretics	↑	↑ ↑	↓ (false negative)
    Ca2+ blockers (dihydropyridine)	→ ↓	↑
    Potassium-wasting diuretics	→ ↑	↑ ↑
    Central alpha-2 agonists (eg, clonidine, α-methyldopa)	↓	↓ ↓	↑ (false positive)
    Nonsteroidal anti-inflammatory drugs
    β-Adrenergic blockers	↓	↓ ↓
    Renin inhibitors	↓	↓ ↑	↑ (false positive); ↓ (false negative)
    Potassium status
    Hypokalemia	↓	→ ↑	↓ (false negative)
    Potassium loading	↑	→ ↓	↑
    Dietary sodium
    Sodium loaded	↓	↓ ↓	↑ (false positive)
    Sodium restricted	↑	↑ ↑	↑ (false negative)
    Age
    >65	↓	↓ ↓	↑ (false positive)
    Premenopausal females***
    Compared with males	→ ↑	↓	↑ (false positive)
    Other conditions
    Malignant hypertension	↑	↑ ↑	↓ (false negative)
    Pregnancy
    Renovascular hypertension
    Pseudohypoaldosteronism type 2	→	↓	↑ (false positive)
    Renal impairment
    *Adapted from Funder, Endocrine Society Guideline, 2016 **Renin inhibitors lower PRA but raise DRC. This would be expected to result in false-positive ARR levels for renin measured as PRA and false negatives for renin measured at DRC. ***In premenopausal, ovulating women, plasma aldosterone levels measured during the menses or the proliferative phase of the menstrual cycle are similar to those of men but rise briskly in the luteal phase. Because renin levels are lower, the ARR is higher than in men for all phases of the cycle, but especially during the luteal phase during which aldosterone rises to a greater extent than renin. False positives can occur during the luteal phase, but only if renin is measured as DRC and not PRA. In preliminary studies, some investigations have found false positives on the current cutoffs for women in the luteal phase. Accordingly, it would seem sensible to screen women at the follicular phase, if practicable.

Confirmatory Testing

• Insufficient evidence to recommend one strategy over another (Funder, Endocrine Society Guideline, 2016)
  • Captopril challenge (CCT)
  • Fludrocortisone suppression (FST)
  • Saline infusion (SIT)
  • Oral sodium loading
• Recent study comparing CCT, furosemide upright test (FUT), and SIT in Japanese individuals (Nanba, 2012)
  • Single confirmatory testing is sufficient to confirm PA; SIT is suboptimal when compared to CCT and FUT
  • Although significantly higher results correlate with unilateral subtypes, adrenal vein sampling (AVS) is still recommended before surgery even in patients highly likely to have unilateral PA

Subtype Differentiation