Clinical utility of chromogranin A for the surveillance of succinate dehydrogenase B- and succinate dehydrogenase D-related paraganglioma. (January 2019)

• Record Type: Journal Article
• Authors: Thompson, Michael JW; Parameswaran, Venkat; Burgess, John R
• Is Part Of: Annals of clinical biochemistry. Volume 56:Number 1(2019:Jan.)
• Page Start: 163
• Page End: 169
• Publication Date: 2019-01
• Subjects: Chromogranin A -- succinate dehydrogenase -- succinate dehydrogenase D -- succinate dehydrogenase B -- paraganglioma -- surveillance; Clinical chemistry -- Periodicals; Clinical biochemistry -- Periodicals; 616.075
• DOI: 10.1177/0004563218811865
• Languages: English
• ISSNs: 0004-5632

Abstract

Background: 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. Methods: 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). Results: 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. Conclusion: 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.