Endocrine Abstracts

Introduction: Chromogranin A (CgA) is a major representative of the protein family named granins stored predominately in secretory granules of the diffuse neuroendocrine system. Circulating CgA serves as a biomarker of neuroendocrine tumors (NETs), but its increased plasma concentration is present in various cardiovascular, gastrointestinal, renal and inflammatory diseases. Intra-granular and/or extracellular proteolysis of CgA generates a variety of biologically active fragments, which seem to beinvolved in the regulation of metabolism (pancreastatin and catestatin), cardiovascular system (vasostatin, catestatin), innate immunity (chromacin), angiogenesis and tissue repair (serpinin). It was shown that in rat models pancreastatin promotes insulin resistance by inhibiting insulin action on glucose and lipid metabolism while low catestatin promotes hypertension. The aim of this study is to analyze correlation between CgA levels and standard metabolic indices in patients with NETs.

Materials and methods: We analyzed 20 patients (mean age 47.5 ± 14.8 yrs) with newly diagnosed well-differentiated gastroenteropancreatic NETs (GEP-NETs), 10 women and 7 men. In all subjects we measured waist circumference (WC), blood pressure (BP), fasting glucose (FG), HbA1c, total cholesterol (TC), HDL, LDL, triglycerides (TG), CgA, glucose and insulin during 2-hour oral glucose tolerance test (OGTT). We calculated body mass index (BMI), markers of insulin resistance (HOMA-IR and Matsuda index), area under the curve (AUC) for glucose and insulin during OGTT and lipid accumulation product (LAP) as a surrogate marker of metabolic syndrome (MetS).

Results: Impaired glucose tolerance was detected in one patient, impaired fasting glucose in two patients and others (17/20) had normal glucose tolerance. Our patients had (mean ± s.d.) CgA 264.9 ± 182.1 ng/ml, HOMA-IR 2.4 ± 1.8, Mathsuda index 4.9 ± 2.3, LAP 66.7 ± 36.5, systolic BP 127 ± 5 mmHg and diastolic BP 81 ± 13 mmHg. CgA correlated with FG (r = 0.572, p = 0.021), Tg (r = 0.532, P = 0.034), systolic BP (r = 0.536, P = 0.039), diastolic BP (r = 0.535, P = 0.040).

Conclusion: This pilot study shows that CgA could serve as a marker of initial derangement of metabolic disturbances in newly diagnosed patients with NETs.