Repeating adrenal vein sampling when neither aldosterone/cortisol ratio exceeds peripheral yields a high incidence of aldosterone-producing adenoma. 
In primary aldosteronism, adrenal vein sampling (AVS) suggests unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol (A/F) ratio is less than or equal to peripheral on one side and at least two times peripheral on the other.  When A/F ratios are lower bilaterally than peripheral despite adequate samples (adrenal venous cortisol ≥3 times peripheral), we recommend repeat AVS.  This study aimed to determine the frequency of this occurrence and outcomes in such cases.  We performed a retrospective observational study of all cases of primary aldosteronism undergoing initial AVS over a 34-year period.  Initial AVS in 1397 patients returned satisfactory and discriminatory results in 1066 (76.3%) but 37 patients (2.6%) had adequate samples but bilateral A/F ratios no higher than peripheral.  Of the 22 of these 37 who agreed to repeat AVS, 10 demonstrated unilateral aldosterone production, and eight of these had unilateral adrenalectomy disclosing APAs and resulting in cure (3) or improvement (5) in hypertension.  Eight had bilateral aldosterone production.  Four studies were inconclusive.  Patients with initial unsatisfactory AVS because of bilaterally low A/F ratios had significantly (P=0.023) more unilateral disease [10 of 18 satisfactory repeat studies (55.6%) vs. 326 of 1066 satisfactory initial studies (30.6%)] and a significantly higher (67.6 vs. 49.9%, P=0.034) percentage of males.  As the incidence of APAs was high in a subgroup with low A/F bilaterally on initial AVS, these patients should be offered repeat AVS.  This might reflect both a greater dependence of aldosterone production on adrenocorticotrophic hormone (ACTH) in APAs and the pulsatile nature of ACTH secretion.