Adrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling for Identifying Surgically Curable Subtypes of Primary Aldosteronism

Abstract

Abstract-Adrenocorticotropic hormone administration was proposed to overcome the biases associated with pulsatile aldosterone secretion during adrenal venous sampling, but the usefulness of different protocols of stimulation was never systematically assessed. We, therefore, compared the effects of a high dose (HD; 250 g IV as a bolus), a very low dose (VLD; 250 pg IV), and an intermediate dose (ID; 50 g/h) of adrenocorticotropic hormone on the selectivity index (SI) and the lateralization index in primary aldosteronism patients, using the diagnosis of aldosterone-producing adenoma, based on pathology and follow-up data, as a reference. The HD (nϭ47) significantly increased plasma cortisol concentration in infrarenal inferior vena cava (ϩ79%) blood and the SI on both sides (SI RIGHT ϩ113% and SI LEFT ϩ131%), as compared with baseline values. The ID (nϭ14) also markedly increased both plasma cortisol concentration inferior vena cava (ϩ93%) and the SI (SI RIGHT ϩ690% and SI LEFT ϩ410%); the very low dose (nϭ6) had no effect on either the plasma cortisol concentration or SI. In the patients with unilateral aldosterone-producing adenoma, the increase of selectivity with the HD and ID was counterbalanced by a confounding effect on the correct identification of the aldosterone-producing adenoma side, which was attributed to the wrong side in 3.0% and 12.5% with HD and ID, respectively. In conclusion, the HD and the ID, but not the very low dose, adrenocorticotropic hormone stimulation protocol facilitated the ascertainment of selectivity of adrenal vein catheterization. However, this favorable effect was overridden by a confounding effect on the identification of lateralized aldosterone excess to the aldosterone-producing adenoma side. Hence, we do not recommend adrenocorticotropic hormone stimulation.

Plasma Metanephrine for Assessing the Selectivity of Adrenal Venous Sampling

“…18,19 In contrast, metanephrine is cleared rapidly from the circulation so that PV concentrations are maintained at much lower levels compared with those at AV sites where most of the metabolite enters the systemic circulation. 7,10 All the above factors likely contribute to the consistently high gradients in PV to AV plasma concentrations of metanephrine, which provide an opportunity for more accurate and sensitive detection of selective AV catheterization than the smaller gradients for cortisol or other substances evaluated for this purpose, such as chromogranin.…”

“…7,10 Third, cortisol is cleared from the circulation slowly, resulting in high peripheral plasma concentrations relative to rates of secretion and consequently relatively small step-ups in concentrations from PV to AV sites of release that are more easily detected by stimulating secretion with cosyntropin. 18,19 In contrast, metanephrine is cleared rapidly from the circulation so that PV concentrations are maintained at much lower levels compared with those at AV sites where most of the metabolite enters the systemic circulation. 7,10 All the above factors likely contribute to the consistently high gradients in PV to AV plasma concentrations of metanephrine, which provide an opportunity for more accurate and sensitive detection of selective AV catheterization than the smaller gradients for cortisol or other substances evaluated for this purpose, such as chromogranin.…”

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). While facilitating the ascertainment of selectivity, it did not eliminate the problems inherent to the stress reaction, particularly when using the sequential AVS technique.…”

“…Hence, the Endocrine Society practice guidelines endorse its systematic use in the PA patients who seek surgical cure (1,2). However, notwithstanding recent improvements (3), unresolved issues concerning the performance and interpretation of AVS still remain (4,5,6,7,8). This prompted a concerted international effort -the Adrenal Vein Sampling International Study (AVIS; http://clinicaltrials.gov/ct2/show/ NCT01234220) -that showed that the major referral centers worldwide are almost equally split between those that have adopted the bilaterally simultaneous catheterization (9) and those using the more traditional sequential technique.…”

“…By enhancing cortisol release, the latter facilitates the ascertainment of selectivity (12), but its usefulness is limited by its confounding effect on the assessment of lateralization of aldosterone excess (8). Hence, it is unlikely that cosyntropin stimulation can provide a final solution to the issue of time-dependent stressrelated effects on AVS results (8). In spite of all these premises, a stress reaction during AVS has never been systematically investigated as yet (13,14,15).…”