Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary?

Abstract

Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery. Despite significant advances in the optimization of the AVS procedure and the interpretation of hormonal data, a standardized protocol across centers is still lacking. Alternative methods are sought to either localize an aldosterone producing adenoma or to predict the presence of unilateral disease and thereby substantially reduce the number of patients with PA who proceed to AVS. In this review, we summarize the recent advances in subtyping PA for the diagnosis of unilateral and bilateral disease. We focus on the developments in the AVS procedure, the interpretation criteria, and comparisons of the performance of AVS with the alternative methods that are currently available.

Adrenal vein sampling with and without cosyntropin stimulation for detection of surgically remediable aldosteronism

“…In summary, the lowest SI tertile (1.5‐2.1) pre‐ACTH stimulation does not reduce the AVS specificity and may increase the SRA yield. Although the predetermined SI post‐ACTHstim was 2.0, the lowest SI encountered was 3.2 consistent with the well‐known observation that ACTHstim increases the SI . Other studies have examined the sensitivity and specificity of different SI, but do not use surgical cure, not biochemical cure, as the outcome .…”

“…In comparison to many prior studies, we used a lower SI limit (1.5 pre‐ACTHstim and 2.0 post‐ACTHstim) to confirm adequate sampling of the adrenal veins. Since we employed a predetermined SI in all patients, then we are in a position to evaluate the performance of this relatively low SI.…”

“…Bilateral adrenal vein sampling (AVS) is considered to be the best diagnostic test for SRA identification . However, there is no consensus as to the best AVS protocol . Approximately two‐third of centres perform AVS following cosyntropin administration .…”

11C‐Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice

“…It is well recognized that AVS presents significant challenges which limit its wider application, including (a) difficulty in successfully cannulating both adrenal veins and (b) lack of consensus in relation to procedural methodology, that is ACTH‐stimulated vs unstimulated, sequential vs simultaneous cannulation. As such, in spite of its “gold standard” status, there is variability of technique and considerable subjectivity of interpretation of the SI and LI from centre‐to‐centre . Sequential, unstimulated AVS has been performed by a single operator (GJO'S) at our centre since late 2014, producing success rates for cannulation of both adrenal veins which are above 97%, when applying a SI of 2.0.…”

“…Additionally, clinically important APAs which co‐secrete cortisol (suppress DHEA‐S and ACTH; lack of dexamethasone suppression), albeit relatively rare, highlight the potential for false‐negative lateralization using AVS by virtue of yielding a lower aldosterone:cortisol on the side of the lesion . Overall, AVS has been reported to yield unsatisfactory or indeterminate results in 15%‐30% of all cases …”