Pre‑Adrenal Venous Sampling Management of Mineralocorticoid Receptor Antagonists

Withdrawal Timing for MRAs

Spironolactone should be stopped at least 6 weeks before adrenal venous sampling (AVS). – American College of Endocrinology & American Association of Clinical Endocrinology recommendation. 1
Eplerenone should be discontinued for a minimum of 4 weeks before AVS. – American College of Endocrinology & American Association of Clinical Endocrinology recommendation. 1
All mineralocorticoid receptor antagonists (MRAs) must be withdrawn for ≥4 weeks prior to AVS to avoid interference with lateralization. – American College of Cardiology (ACC) consensus. 2

MRAs can stimulate aldosterone secretion from the contralateral (normal) adrenal gland, lowering the lateralization index and potentially producing false‑negative AVS results that would inappropriately exclude patients from curative surgery. – American College of Endocrinology & American Association of Clinical Endocrinology evidence. 1

Use antihypertensive agents that do not affect the renin‑angiotensin‑aldosterone system (e.g., alpha‑blockers such as doxazosin, prazosin, terazosin; vasodilators such as hydralazine, diltiazem, verapamil, nifedipine). – Endocrine Society guidance; supported by ACC data on permissible medications. [3][4]

Correct hypokalemia before AVS because low serum potassium suppresses aldosterone secretion and may cause false‑negative lateralization. – Endocrine Society recommendation. 3
Serum potassium should be normalized (within the laboratory reference range) before AVS. – ACC consensus on electrolyte optimization. 2
Maintain unrestricted dietary salt intake during the preparation period to avoid compensatory aldosterone stimulation. – Endocrine Society recommendation. 3

Measure plasma renin activity (PRA) immediately before AVS; a PRA < 0.5 ng/mL/hr (or direct renin concentration < 25 mIU/L) indicates adequate suppression and reliable lateralization. – Endocrine Society criteria for adequate preparation. 3

Computed tomography (CT) concordance with AVS is limited (approximately 62 % agreement); therefore imaging alone should not be used to determine lateralization. – Endocrine Society data. 3

In patients younger than 35–40 years who have marked primary aldosteronism, spontaneous hypokalemia, a unilateral adrenal adenoma > 1 cm on CT, and a normal contralateral gland, AVS may be omitted and adrenalectomy performed directly. – American Association of Clinical Endocrinology guideline; supported by Endocrine Society evidence on low incidentaloma prevalence in this age group. [5][3]

All mineralocorticoid receptor antagonists (including spironolactone and eplerenone) must be discontinued at least 4 weeks before adrenal venous sampling (AVS). This interval is required to eliminate drug‑induced stimulation of aldosterone secretion that can falsely lower the lateralization index. [ACC/AHA 2018 guidelines] 6, 7, 8

Antihypertensive agents that do not interfere with the renin‑angiotensin‑aldosterone system are recommended as bridge therapy while MRAs are withdrawn. Suitable classes include:
- Alpha‑blockers (e.g., doxazosin, prazosin, terazosin)
- Non‑dihydropyridine calcium‑channel blockers (e.g., diltiazem, verapamil)
- Dihydropyridine calcium‑channel blockers (e.g., nifedipine)
- Direct vasodilators (e.g., hydralazine)

Serum potassium must be corrected to the laboratory reference range before AVS. Hypokalemia suppresses aldosterone secretion and can produce false‑negative lateralization results. [Canadian Cardiovascular Society 2020] 10
Plasma renin activity (or direct renin concentration) should be measured immediately before AVS to confirm adequate renin suppression (PRA < 0.5 ng/mL/hr or direct renin < 25 mIU/L). This confirms that the withdrawal period has been sufficient for reliable interpretation. (derived from guideline practice; no separate citation needed)

Patients should maintain unrestricted dietary sodium intake during the pre‑AVS preparation. Sodium restriction would provoke compensatory aldosterone release from both adrenal glands, confounding lateralization assessment. [ACC/AHA 2018 guidelines] 6, 7, 8

ACE inhibitors and angiotensin‑receptor blockers must be discontinued during the MRA withdrawal period. These agents also affect the renin‑angiotensin‑aldosterone system and should be replaced with the non‑interfering antihypertensives listed above. [ACC 2025 guideline] 9