Clinical utility of chromogranin A in SDHx-related paragangliomas.
BACKGROUND
Measurement of plasma/urinary catecholamine metabolites--especially normetanephrine (NMN)--represents a gold standard in biochemical detection of succinate dehydrogenase subunit B (SDHB) and D (SDHD)-related pheochromocytomas (PHEO) and paragangliomas (PGL). This study was designed to assess diagnostic utility of chromogranin A (CgA) alone or in combination with NMN in patients with PHEO/PGL related to mutations in SDHB and SDHD.


METHODS
A retrospective study of SDHB and SDHD NIH patients' cohort, which included 41 patients with SDHB mutation-related PHEO/sPGL and 18 patients with either SDHD or SDHB mutation-related head and neck PGL (HNPGL) with both CgA and NMN measured at the time of diagnosis at NIH.


RESULTS
In the SDHB group, CgA showed sensitivity of 73.2% and specificity of 95.9%, while for NMN they were 70.7% and 98.6%, respectively. Elevations in CgA and NMN were complementary in 92.7% of patients with proven tumors. Both tests performed well on receiver operating characteristic curve analysis. CgA levels were elevated in 76.9% of SDHB patients and in 80% of patients with metastatic disease and normal NMN levels. CgA values in patients with HNPGL were significantly lower than in patients with PHEO/sPGL.


CONCLUSIONS
CgA is a valuable complementary biomarker in work-up of SDHB-related PHEO/sPGL. In combination with plasma NMN, CgA further enhances tumor detection by 22.0% with minimal loss in specificity. Although non-specific for PHEO/PGL, CgA may well supplement plasma NMN to facilitate diagnostic evaluation of SDHB-related PHEO/sPGL, especially where the measurement of plasma metanephrines could otherwise be delayed by decreased availability or cost restriction.
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Samuel
S
Zuber
Robert
R
Wesley
Tamara
T
Prodanov
Graeme
G
Eisenhofer
Karel
K
Pacak
Vitaly
V
Kantorovich
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D053379:Chromogranin A / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009647:Normetanephrine / Q000378:metabolism; D010235:Paraganglioma / Q000175:diagnosis* / Q000235:genetics; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D053379:Chromogranin A; C491545:SDHD protein, human; D009647:Normetanephrine; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase
Chromogranin A; SDHD; metanephrines; metastatic SDHB; paraganglioma; pheochromocytoma