Endocrine Abstracts

Introduction: Pheochromocytomas (PHEO) and paragangliomas (PGL) - (PPGLs) are neuroendocrine tumors derived from chromaffin cells of the adrenal medulla or extraadrenal nonchromaffinic tissue, respectively. PPGLs occur in 0.05% to 0.1% of patients with secondary hypertension. Chromogranin A (CgA) is the main non-specific biomarker of neuroendocrine tumors. It is produced and secreted into the blood by endo- and neuroendocrine cells of various organs (e.g., adrenal glands). The sensitivity of the determination of this biomarker in the diagnosis of pheochromocytoma exceeds 80%-90%. Current immunoassays for the determination of CgA concentrations in the blood differ from each other, e.g. they recognize different fragments of CgA, are calibrated differently, and use different antibodies (monoclonal/polyclonal).

Aim of the study: The aim of this study was to compare the determination of CgA concentrations and the CgA/URL (Chromogranin A concentration/Upper Reference Limit) ratio by different immunochemical methods in patients with PPGLs diagnosed in two European centers (Poland and Sweden).

Materials and Methods: The analysis included 161 patients with PPGLs from 2 centers: Poland (PHEO 63, PGL 7) and Sweden (PHEO 74, PGL 17). Serum or plasma CgA concentrations were determined by various immunochemical methods (RIA, IRMA and ELISA), and plasma metanephrine and normetanephrine concentrations were determined by chromatographic methods (LC-MS/MS or HPLC-ECD) in all subjects. Reference range for the tests: CgA<98 ng/ml (Poland), CgA<3 nmol/l (Sweden). Results are presented as concentration ranges (median) and CgA/URL ratio (multiplicity URL).

Results: In the patient population (Poland), CgA concentrations in patients with PHEO were in the range of 16-1234 ng/ml (median 176.8 ng/ml), while the CgA/URL_PHEO ratio was 0-12. In PGL patients, the range of CgA concentration was 46-772.5 ng/ml (median 98 ng/ml), and the CgA/URL_PGL ratio was 0-8. In the patient population (Sweden), CgA concentrations in patients with PHEO were in the range of 1.0 - 367.0 nmol/l (median 8.85 nmol/l), while the CgA/URL_PHEO ratio was 0 - 122. In PGL patients, the range of CgA concentration was 1.1-23.0 nmol/l (median 6.9 nmol/l), while the CgA/URL_PGL ratio was 0-6.7.

Conclusions: The CgA/URL ratio in PPGLs is more useful than the determination of blood CgA concentration in the comparative diagnosis of patients diagnosed at different centers and allows clinical comparison of different immunoassays used in routine clinical diagnosis.