Subtyping of primary aldosteronism with adrenal vein sampling: Hormone- and side-specific effects of cosyntropin and metoclopramide

BACKGROUND: Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization index in consecutive primary aldosteronism patients submitted to adrenal vein sampling. METHODS: We recruited 171 patients; of these, 149 underwent adrenal vein sampling before and after stimulation with cosyntropin (250 µg intravenous bolus, n= 53, 73% with an aldosterone-producing adenoma) or with metoclopramide (10 mg intravenous bolus, n= 96, 65% aldosterone-producing adenoma), and 32 with an aldosterone-producing adenoma were investigated for the relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine (serotonin) 4 receptor with microarrays. Cosyntropin increased the selectivity index similarly on both sides; metoclopramide did not. Cosyntropin decreased relative aldosterone secretion index on the aldosterone-producing adenoma side but not contralaterally. Metoclopramide did not affect the selectivity index, but increased the relative aldosterone secretion index similarly on both sides. Because of these changes, cosyntropin decreased the lateralization index, while metoclopramide did not affect it. The relative gene expression of melanocortin 2, albeit heterogeneous across tumors, was 35% less (P<.0001) in aldosterone-producing adenoma than in the normal adrenal cortex, while dopamine receptor D2 and 5-hydroxytryptamine (serotonin) 4 receptors did not differ between tissues. CONCLUSION: Cosyntropin, while facilitating ascertainment of selectivity, lessens the lateralization, likely because of a blunted melanocortin 2 expression in aldosterone-producing adenoma. The similar expression of dopamine and 5-hydroxytryptamine (serotonin) 4 receptors in aldosterone-producing adenoma and the normal adrenal cortex can explain why metoclopramide increased the relative aldosterone secretion index on both sides and, therefore, failed to increase the lateralization index. (Surgery 2017;160:XXX-XXX.).