Physiologic variance of corticotropin affects diagnosis in adrenal vein sampling

Abstract

Objective: Differentiating unilateral form from bilateral is a critical diagnostic step in primary aldosteronism (PA), for which adrenal vein sampling (AVS) is accepted to be the most reliable. However, variance of corticotropin could affect the diagnosis in AVS. Design and methods: We conducted simultaneous bilateral AVS on ten biochemically diagnosed PA cases, and used the aldosterone-to-cortisol ratio (A/C) of the samples for the diagnosis. The diagnosis by AVS after a low-dose (0.1 mg) ACTH stimulation, which can provoke maximum-physiologic corticotropic response, was compared with those before the stimulation and after the standard-dose (250 mg) ACTH stimulation. Results: In half of the cases, the low-dose pre-stimulation affected the diagnosis. In four out of ten cases, the side-to-side ratios of A/C were changed in the basal/low-dose/standard-dose AVS as 6.62/2.46/0.63, 2.13/0.41/0.14, 1.88/2.38/2.40, and 1.96/2.27/1.90 respectively. In three out of ten cases, the adrenal vein to the matching inferior vena cava ratio of A/C was also changed across 1, the cut-off to indicate suppression of aldosterone secretion. Additionally, the confirmation of successful sampling was difficult in five out of ten and two out of ten cases of the basal and low-dose AVS respectively, whereas it was easy in all the cases of the standard-dose AVS. Conclusions: The diagnosis in the basal AVS could be affected by the physiologic fluctuation of ACTH at relatively high prevalence. The basal AVS would be unreliable to differentiate two forms of PA.

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

“…In agreement with emerging findings from other groups, 5,6,13,14 the above considerations conversely imply that cortisol provides a less than optimal parameter to establish selective catheterization in nonstimulated sequential AVS procedures. This conclusion is reinforced by our findings that metanephrine to normetanephrine and epinephrine to norepinephrine ratios in most nonstimulated AV samples designated nonselective, based on a cortisol-derived selectivity index of 3.0, were well above the range for ratios in PV samples and within the range for the AV samples designated as selective.…”

“…First, as demonstrated by others, [4][5][6] adrenal secretion of cortisol fluctuates so that AV plasma concentrations during periods of low secretion may be only slightly higher than those in peripheral plasma, providing the rationale for cosyntropin stimulation. In contrast, metanephrine is produced continuously within adrenal medullary cells from epinephrine leaking from storage vesicles, a process that is independent of fluctuations in epinephrine release.…”

“…Furthermore, as a result of physiological corticotropin fluctuations, cortisol is secreted in a variable fashion so that fluctuating levels can interfere with the interpretation of AVS selectivity. [4][5][6] This problem can be overcome using cosyntropin stimulation. 7 Cosyntropin stimulation, however, adds to the complexity of the procedure and for this reason is not always used.…”

Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is useful in centers with low success rates

“…One of the advantages of ACTH 1-24 infusion may be a higher step up between peripheral and adrenal vein cortisol values and thus a higher percentage of successful studies. However, the effects on lateralization and thus on diagnosis are not that clear-cut: in a relatively small study with ten patients undergoing AVS first without and then with ACTH 1-24 infusion the authors noted a lateralization toward the wrong side for the values sampled at baseline, suggesting that concomitant ACTH 1-24 infusion might increase the diagnostic reliability (17). A larger study comparing baseline with bolus and continuous infusion of ACTH 1-24 found a completely different effect, claiming that ACTH 1-24 infusion improved the percentage of successful samplings but reduced the number of correctly diagnosed APAs (18).…”

A stress reaction affects assessment of selectivity of adrenal venous sampling and of lateralization of aldosterone excess in primary aldosteronism

“…To minimize the impact of these factors, ACTH infusion was introduced by Weinberger et al (22) and widely used thereafter (21,23,24), thus being held as an essential part of the sequential AVS (11,19,21,25), or even of bilaterally simultaneous AVS (5,26,27). In our hands, cosyntropin stimulation confounded the assessment of lateralization and led to misclassification of the APA side (8,17).…”