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 µg/L for children aged 0–3 years, 18–85 µg/L for children aged 4–13 years, and 6–79 µg/L for adolescents aged 14–19 years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102 µg/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39 µg/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.