Abstract

Background: Adrenal vein sampling (AVS) is the test of choice for subtyping primary aldosteronism (PA). Paradoxical bilateral aldosterone suppression (BAS), defined by lower aldosterone/cortisol ratios in both adrenal veins (AV) compared to periphery, is found in some AVS studies, but the underlying causes remain unclear. Objectives: To understand the factors leading to BAS in PA patients and to comprehensively analyze the steroid profiles of these patients. Methods: We first retrospectively reviewed the records of all patients with confirmed PA who underwent AVS in our institution between January 2009 and October 2018, and we collected demographic, diagnostic, subtyping and follow up data for all cases. Simultaneous AVS was performed both before and after cosyntropin (ACTH) stimulation. LC-MS/MS analysis of 17 steroids was done in all cases where serum was available. Results: Of 297 patients with PA included in our study, BAS was observed in 41 (13.8%) patients: both pre- and post-ACTH in 10 patients, only pre-ACTH in three patients, and only post-ACTH in 28 patients (in 11 of these, successful catheterization was confirmed successful only after ACTH administration). Most BAS patients were men (78% vs 56% of patients without BAS, p<0.01). Bilateral PA was diagnosed in 31/41 (76%) with BAS, as compared to 102/252 (40%) patients without BAS (p<0.0001) based on post-ACTH data; and in 16/30 (53%) vs 74/209 (35%) of patients with vs. without BAS (p=0.07) with successful pre-ACTH catheterization. Peripheral aldosterone concentrations were significantly higher in patients with bilateral PA and BAS than those without BAS, both pre- and post-ACTH stimulation (29 vs. 14, and 40 vs. 23 ng/dL, respectively, p<0.001), while no significant differences were found between patients with unilateral PA with and without BAS. Of the 23 patients with BAS based on clinical data who had serum available for LC-MS/MS steroid quantitation, aldosterone/cortisol did not show BAS in 17 (74%) patients, and lateralization changed from bilateral to unilateral PA in two patients. Anomalous venous drainage was not found on AVS imaging review in the remaining cases. When comparing patients diagnosed with bilateral PA and BAS (n=19) vs. those without BAS (n=51) based on clinical data, all non-sex steroids were similar between the two groups in peripheral serum. Of 14 BAS patients who underwent adrenalectomy, including three patients with BAS confirmed with LC-MS/MS, all had clinical success (two complete and 12 partial) and 8/8 patients had complete biochemical success after surgery. Conclusions: BAS appears to derive mainly from artifacts in clinical immunoassays, more commonly in men. Cases with BAS and unilateral PA are rare, and while genesis of this pattern remains obscure, such cases still benefit from surgery.

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