Introduction Pediatric obesity is a major health problem. It is generally thought that it is rarely caused by an underlying condition, but evidence is limited. Aim of this study was to establish the diagnostic yield of an extensive obesity workup in a pediatric obesity cohort. In addition, we assessed the accuracy of the diagnostic criteria of the Endocrine Society (ES) Guideline for pediatric obesity.

Methods In this prospective observational study, data from obesity center CGG, a Dutch multidisciplinary clinic for diagnostics and treatment of obesity, was analyzed. In total, 280 children referred to the outpatient CGG clinics of collaborating centers (Maasstad Hospital, Franciscus Gasthuis and Erasmus MC-Sophia) were included. Data on personal, behavioral, anthropometric and family characteristics were obtained as well as hormonal evaluation, and genetic testing (NGS gene panel, SNP array, additional diagnostics when indicated). Sensitivity and specificity of the diagnostic recommendations of the ES Guideline were calculated using our diagnostic workup as external standard.

Results Median age was 10.9yr (IQR 7.7-14.1); mean BMI-SDS +3.8 (SD 0.9). A definite underlying diagnosis was established in 51 (18.2%) children: 34 genetic, 8 medication-induced, 9 hypothalamic obesity. In an additional 29 (10%) children, a possibly obesity-causing genetic variant was identified, probably increasing the number of diagnoses in the cohort. Application of the current ES Guideline would have identified 35/51 diagnoses (sensitivity 69%; specificity 59%).

Discussion We show a high diagnostic yield (18.2%) of underlying causes of obesity in a specialized pediatric obesity center. No more than two-third of these diagnoses would have been picked up following the current ES Guideline. Further studies into predictors of underlying causes might help in improving its diagnostic accuracy. Identifying underlying causes of obesity is crucial for patient-tailored treatment, especially with novel drugs targeting the leptin-melanocortin pathway showing promising results in clinical trials.