Clinical utility of chromogranin A for the surveillance of succinate dehydrogenase B

Patients with mutations of succinate dehydrogenase B (SDHB) and succinate dehydrogenase D (SDHD) are at high risk of paraganglioma necessitating surveillance. Chromogranin A has been proposed as a biochemical marker of paraganglioma. We sought to determine the diagnostic utility of chromogranin A in a population-based SDHx sample. Tasmania is an island state with one tertiary referral centre for endocrine neoplasia. We performed a cross-sectional analysis of all adult SDHB (n？=？52) and SDHD (n？=？10) patients undergoing paraganglioma surveillance between 2011 and 2017. Chromogranin A was referenced against the outcome of paraganglioma surveillance with a minimum of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and plasma metanephrines (metanephrine and normetanephrine). Chromogranin A correctly predicted the result of paraganglioma surveillance more often in patients with SDHB compared with those with SDHD (77% vs. 22%, P？=？0.003). In the SDHB group, chromogranin A demonstrated a sensitivity of 67% and specificity of 79% compared with 22% and 0% in the SDHD group. Chromogranin A identified one of three PET/CT-visualized SDHB-related paragangliomas with normal plasma metanephrines at the expense of nine false-positive results. A normal chromogranin A demonstrated a negative predictive value of 92% for SDHB-related paraganglioma. In patients with SDHB, plasma normetanephrine and metanephrine offered superior specificity (100%, P？=？0.01 and 100%, P？<？0.01, respectively) with comparable sensitivity (67%, P？=？1.0 and 11%, P？=？0.06, respectively) to chromogranin A. Chromogranin A does not provide additive benefit to standard surveillance for predicting the presence of SDHB- or SDHD-related paraganglioma, but has a useful negative predictive value when normal in patients with SDHB mutation