Subtyping of Primary Aldosteronism by Adrenal Venous Sampling

Abstract

Primary aldosteronism (PA), the most common cause of arterial hypertension, is surgically curable if a unilateral source of the hyperaldosteronism is discovered. To identify which patients are curable, all current guidelines recommend adrenal venous sampling (AVS), a procedure which, albeit simple in principle, remains scarcely available and markedly underutilized, because it is still perceived as technically challenging, invasive, and difficult to interpret. The lack of uniformly accepted standards for performance and interpretation of AVS, alongside the diffuse concerns that (although quite rarely) it can be complicated by adrenal vein rupture, contribute to the scant utilization of AVS. In the last decade, several major studies have led to a greater understanding of the use of AVS in PA patients, thus paving the way to a more rational and effective application that can enable diagnosis of many more PA patients with a unilateral form of the disease to be referred for curative adrenalectomy. Moreover, microcatheters and androstenedione have been introduced to increase the success rate. This review provides updated information on the subtyping of PA by means of AVS and examines key issues on the selection and preparation of patients, the optimal performance of the procedure, and the interpretation of its results for diagnostic purposes, even in the most challenging cases. Situations when AVS can be omitted before surgery and alternative functional imaging techniques that have been proposed to identify unilateral surgical curable PA to circumvent the bottleneck represented by the limited availability of AVS worldwide, are also discussed.

Keywords: adrenal vein sampling; aldosterone; diagnosis; endocrine hypertension; hyperaldosteronism subtypes; primary aldosteronism.

Graphical Abstract

Figure 1.

Results from the AVIS-2-imaging study show that imaging alone by CT or MRI scanning is not accurate for identifying the culprit adrenal because 34% of the patients with confirmed PA have no detectable nodules and about 8% have bilateral nodules. These data emphasize the importance of AVS for correctly referring patients for adrenalectomy.

Figure 2.

The flow chart shows the algorithm that can be used to select the patients who need to be submitted to AVS. Those who have an indication to surgery because of a large tumor suspicious of adrenal carcinoma, have contraindications to general anesthesia and/or surgery, do not wish to have surgery, or have familial hyperaldosteronism should not be offered AVS. Based on the results of the AVIS-2 Young Study, young patients (≤45 years) can be referred for adrenalectomy without AVS if they have a unilateral adrenal nodule at imaging with a contralateral normal-appearing adrenal, and hypokalemia, because their chance of having uPA due to the contralateral adrenal is close to 0.

Figure 3.

The cartoon illustrates the concept that the performance of AVS can be overridden, and indication for surgery can be posed directly in specific categories of PA patients with cumulative defined clinical features, including age ≤45 years, a unilateral adrenal nodule at imaging with a contralateral normal-appearing adrenal, and hypokalemia, because their chance of having uPA due to the contralateral adrenal is close to 0. However, of all the PA patients submitted to AVS in the AVIS-2 Study, only 29% were ≤45 years and those fulfilling the other criteria were 29% of them. [Adapted with Permission from Rossi GP,  Hypertension 2022; 79 (1) ©American Heart Association, Inc. Wolters Kluwer Health, Inc.].

Figure 4.

The bar graphs show how use of restrictive SI and LI values both under unstimulated and cosyntropin-stimulated conditions leads to decrease the number of PA patients who are diagnosed with uPA and therefore referred for adrenalectomy. [Adapted with Permission from Rossitto G et al  J Clin Endocrinol Metab. 2020;105(6):2042–2052. © Endocrine Society].

Figure 5.

The bar graphs show the distribution of the values of the relative aldosterone secretion index (RASI) in the PA patients submitted to AVS in the AVIS-2 Study, who had selective AVS results on at least one side and were eventually diagnosed with uPA by the 5 corner criteria (upper plot) or presumed to have bilateral PA (bottom panel). Please note the skewed distribution of the values in the former and not in the latter patients, indicating that a RASI value >2.55 or less 0.96 identified the culprit and the contralateral adrenal in the former, thus suggesting that use of the RASI value can support the clinical decision making even when AVS was selective only on one side. [Adapted with Permission from Rossi GP,  Hypertension 2023; 80 (10) ©American Heart Association, Inc. Wolters Kluwer Health, Inc.].