Paediatric reference ranges for plasma chromogranin A

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare diseases with varied aggressiveness originating from endocrine cells belonging to the diffuse endocrine system and most often produce and secrete chromogranin A (CgA). CgA in plasma is therefore used to screen, diagnose, and monitor for NENs in both adults and children with sporadic or familial NENs. Methods: Plasma CgA was measured using the Brahms Kryptor assay in 268 healthy children/adolescents; 85 children were tested as part of a familial cancer screening program and 183 additional children younger than 20 years of age underwent screening for allergies. Repeated measurements (month - years) was used to calculate the intra-individual variation. The dataset was analysed in R using the referenceInterval package. Results: The plasma CgA concentration decreased with age and was 32-118 mu g/L for children aged 0-3 years, 18-85 mu g/L for children aged 4-13 years, and 6-79 mu g/L for adolescents aged 14-19 years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102 mu g/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39 mu g/L, respectively. The median intra-individual variation was 14% (25%-centile 9.4%/75%-centile 21%). Conclusions: The reference interval will be useful when screening, diagnosing, and monitoring children for NENs respecting the limitations plasma CgA has.