What is the role of adrenal vein sampling (AVS) in the diagnostic workup of primary aldosteronism (PA)?

A: Aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia (BAH) account for 98% of PA cases, while the remaining 2% include rare familial subtypes such as unilateral primary adrenal hyperplasia and adrenal carcinoma. Management of PA depends on differentiating these subtypes. Unilateral etiologies can be cured surgically, whereas bilateral causes are treated with therapeutics.

AVS is the gold standard for localizing unilateral APA and distinguishing adenomas from BAH, and studies show that this method alters clinical management in 35.7% of PA patients who would have otherwise received improper treatment based on the results of computerized tomography or other screening modalities.

What are the potential limitations and pitfalls of AVS?

Left adrenal vein catheterization is rarely difficult, given the left vein’s favorable anatomy and low structural variance. By contrast, right adrenal vein cannulation is challenging, and is responsible for the majority of the reported technical failures with AVS. Because of the difficulty of placing the catheter tip within the small adrenal veins, the sample is often obtained from near the orifice of the vein, where the concentration of adrenal hormones is diluted by other blood.

The simultaneous measurement of cortisol concentrations can be used to correct for this dilution and determine the adequacy of the cannulation. However, there is a considerable lack of standardization among labs for interpreting results, with cutoffs for the ratio of adrenal vein-to-external iliac vein cortisol (known as the selectivity index) ranging widely from 1.1 to 5. Controversy also exists about the threshold distinguishing unilateral from bilateral hypersecretion, whether by comparing the cortisol-corrected aldosterone output between the dominant and nondominant side (lateralization index) or the ratio of cortisol-corrected aldosterone concentration between the nondominant side and the external iliac vein (contralateral suppression index). This use of differing AVS cutoffs can have a profound impact on the diagnostic conclusions reached. Furthermore, additional debate surrounds the use of adrenocorticotropic hormone stimulation to minimize time-related variability in hormone concentrations in the adrenal vein blood.

How can intraprocedural laboratory testing confirm the success of adrenal vein cannulation?

Normally, hormonal data does not allow practitioners to judge the selectivity of AVS until after the procedure. In contrast, cortisol measurement during AVS can overcome technical difficulties by giving the radiologist immediate feedback on whether selective blood sampling from each adrenal vein was achieved. This enables further attempts at cannulation until cortisol measurements demonstrate the success of the sampling, thus avoiding the need for future catheterization.

In our institution, during AVS we perform a rapid automated cortisol assay near the radiology operating suite according to a sequential blood collection protocol. If the adrenal catheters are positioned appropriately, cortisol levels obtained from the adrenal catheters are commonly 10 times the value obtained from the peripheral sheath, though a level only 2–3 times the peripheral value is adequate to confirm catheter placement. We have found this intraoperative cortisol assay to be safe, reproducible, simple to perform, rapid, and cost-effective. With the use of intraprocedural cortisol, the success rate of AVS conducted by a radiologist at the plateau phase of performance improved from 80% (without cortisol assays) to 92%. Furthermore, intraprocedural cortisol testing can provide radiologists with an awareness of previously failed attempts that could be relevant as a self-training confirmation or exclusion with respect to morphological views.

In centers where a more rapid approach is not available, a routine cortisol assay could also improve the AVS success rate, provided that the time of the preanalytical phase is minimized and the assay is performed immediately.

Giulio Mengozzi, MD, is director of the clinical biochemistry laboratory at the Città della Salute e della Scienza University Hospital of Turin, Italy. He also serves as an academic educator at the School of Medicine, Biology, Chemistry and Pharmacology, University of Turin. +Email: gmengozzi@cittadellasal