Subtyping primary aldosteronism by inconclusive adrenal vein sampling: A derivation and validation study in a tertiary centre

Abstract

Objective: Indices based on aldosterone/cortisol (A/C) concentration in the successfully cannulated adrenal vein (AV) and in the inferior vena cava (IVC) (AV/ IVC) appear to be possible markers to verify the subtype of primary aldosteronism (PA) in the case of inconclusive results of adrenal vein sampling (AVS). The variability of results in previous studies encouraged us to calculate AV/IVC and adrenal A/C cutoff values that could predict the aetiology of PA. Methods: This retrospective study included 96 patients who underwent AVS due to PA between 2015 and 2020. The derivation cohort ultimately consisted of 60 patients with bilaterally successful AVS and a clear diagnosis of unilateral or bilateral disease. Receiver operating characteristic analysis was used to find the optimal A/C and AV/IVC cutoff values predicting the subtype of PA. The validation cohort consisted of 11 patients with either unsuccessful cannulation or a borderline lateralization index (LI), those patients underwent adrenalectomy because their indices were suggestive of unilateral disease based on the derivation cohort data. Results:The cutoff values of A/C ≤ 0.63 or AV/IVC ≤ 0.37 identified unaffected glands with a sensitivity of 91.2% and 97.1%, respectively, and a specificity of 90.7% and 88.4%, respectively. Unilateral ipsilateral gland involvement was characterized by A/C ≥ 3.5 or AV/IVC ≥ 3.4 with a corresponding specificity of 100%. All patients in the validation cohort achieved biochemical remission postoperatively.Conclusions: A/C and AV/IVC cutoff values could be a useful tool to determine the subtype of PA in patients with unilateral successful AVS as well as in patients with a borderline LI.

Subtyping primary aldosteronism by inconclusive adrenal vein sampling

“…Of greater significance, among the patients with "inconclusive" AVS and only unilateral cannulation success, 3 out of 4 achieved AC > 3.5 or AV/IVC > 3.4 for the affected gland and the one patient with left-sided suppressed AV/IVC did not achieve the suppression index of A/C ≤ 0.63 or AV/IVC ≤ 0.37. Therefore, the cutoffs proposed by Tomsic et al 1 appear conservative in our opinion and would have consigned two out of our five patients with "inconclusive" AVS to long-term medical therapy rather than curative surgery. Notably, we report a biochemical remission rate of 100% and a clinical remission rate of 80% in our small cohort of patients with successful and "inconclusive" AVS.…”

“…To the Editor, We read the article by Tomsic et al 1 on the role of subtyping primary hyperaldosteronism (PA) with inconclusive adrenal vein sampling (AVS), with great interest. Although AVS remains the gold standard procedure for subtyping PA, successful bilateral cannulation remains a challenge for centres with low procedure volume.…”

“…We analysed the cutoffs proposed by Tomsic et al 1 for aldosterone/cortisol concentration ratio (AC) in successfully cannulated AV and adrenal vein to inferior vena cava (AV/IVC) in our cohort of 15 patients with PA undergoing unilateral adrenal surgery in the last 3 years at our institution (Table 1), based on AVS results and imaging findings. Our AVS protocol is similar to that of Tomsic et al 1 Although successful bilateral sampling was only achieved in 10/15 (67%), all 15 patients achieved biochemical remission following unilateral adrenalectomy (defined by aldosterone:renin < 30 pmol/mIU, or random aldosterone ≤ 140 pmol/L). In those with successful AVS, 9/10 (90%) achieved AC > 3.5 or AV/IVC > 3.4 for the affected gland and 7/10 (70%) achieved A/C ≤ 0.63 or AV/IVC ≤ 0.37 for the suppressed gland.…”

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion

“…AVS is required in bilateral PA (including the ACS subgroup), and aldosterone as well as cortisol should be assessed; the procedure is not automatically available in many centres, and sometimes the results are inconclusive or display a high variability in PA, despite an experienced team [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. However, AVS brings supplementary information to imaging procedures allowing better surgical decisions, with a success rate of 76–90%, and the presence of concomitant cortisol excess is mandatory for assessment [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 104 , 105 ].…”

Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism

“…Several studies have suggested that, in the event of failed cannulation of one adrenal veins, the unilateral index, namely the aldosterone-cortisol ratio of the adrenal vein divided by the same ratio in the inferior vena cava (IVC), can distinguish between unilateral and bilateral primary aldosteronism [23][24][25][26][27][28][29][30][31][32]. Most studies have reported the unilateral AV/IVC index using ACTH-stimulated AVS [24][25][26][27][28][29][30]32]. One study reported the index based on non-ACTH stimulated AVS [23], which is common practice in many centres.…”