Clinical utility of chromogranin A for surveillance of succinate dehydrogenase B- and D-related paraganglioma

Background: Patients with mutations of succinate dehydrogenase B (SDHB) and D (SDHD) are at high risk of paraganglioma (PGL) necessitating surveillance. Chromogranin A (CgA) has been proposed as a biochemical marker of PGL. We sought to determine the diagnostic utility of CgA in a population based SDHx sample.

Methods: Tasmania is an island state with one tertiary referral centre for endocrine neoplasia. We performed cross sectional analysis of all adult SDHB (n = 52) and SDHD (n = 10) patients undergoing PGL surveillance between 2011 and 2017. CgA was referenced against the outcome of PGL surveillance with a minimum of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and plasma metanephrines (metanephrine and normetanephrine).

Results: CgA correctly predicted the result of PGL surveillance more often in patients with SDHB compared to those with SDHD (77% vs 22%, p = 0.003). In the SDHB group, CgA demonstrated a sensitivity of 67% and specificity of 79% compared to 22% and 0% in the SDHD group. CgA identified one of three PET/CT-visualised SDHB-related PGLs with normal plasma metanephrines at the expense of nine false positive results. A normal CgA demonstrated a negative predictive value of 92% for SDHB-related PGL. 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 CgA.

Conclusion: CgA does not provide additive benefit to standard surveillance for predicting the presence of SDHB- or SDHD-related PGL, but has a useful negative predictive value when normal in patients with SDHB mutation.