Background: Underlying causes of obesity are thought to be rare even in specialized paediatric endocrinology clinics. However, evidence is limited. The Endocrine Society (ES) guideline for paediatric obesity makes the following diagnostic recommendations: endocrine evaluation in presence of reduced growth velocity, evaluation of cerebral obesity in presence of CNS injury, re-evaluation of drug choice in patients using antipsychotics. Genetic testing is recommended in presence of early-onset obesity <5 years combined with clinical features of genetic obesity disorders (e.g. hyperphagia) and/or family history of extreme obesity. Aim of this study was to evaluate performance of these diagnostic recommendations.
Methods: In this prospective observational study, children and adolescents with obesity visiting a specialized paediatric obesity centre were included. Extensive evaluation of endocrine, genetic, cerebral, medication-induced and lifestyle-induced causes of obesity was performed in all patients. Endocrine, cerebral, and medication-induced obesity were diagnosed only if onset of the underlying cause coincided with a clear slope discontinuity in the patient's growth charts. Genetic testing included next-generation sequencing panel of obesity-associated genes and microarray analysis. Lifestyle-induced obesity was diagnosed only in patients without a somatic diagnosis in whom the paediatric endocrinologist had clear arguments that lifestyle factors played the main role, e.g. changes in lifestyle factors coinciding with clear slope discontinuities in the growth charts. Performance of the guideline recommendations was evaluated using our extensive workup as external standard.
Results: We included 282 patients (59% female). Median age was 10.8 years (IQR 7.7-14.1); median BMI SDS +3.7 (IQR +3.3-+4.3). In 53 (19%) patients, underlying obesity causes were present: 36 genetic, 9 medication-induced, 8 cerebral. In 69/282 (25%) patients, lifestyle-induced obesity was diagnosed. The recommendations would have suggested diagnostics in only 36/53 patients with an underlying cause (sensitivity 68%; 95% CI 55%-79%). The ES guideline criteria 'age of onset <5 years' and 'hyperphagia' were discriminative for underlying diagnoses (p-value <0.001 vs lifestyle-induced obesity), whereas 'family history of extreme obesity' was not (p-value 0.09). Moreover, patients presenting with genetic obesity syndromes with typical onset of obesity >5 years (e.g., 16p11.2 deletion, Temple syndrome) and patients using weight-inducing medication other than antipsychotics would not have been identified if the guideline recommendations had been followed.
Conclusion: We here show that an extensive diagnostic work-up identified 32% more patients with underlying causes of obesity than the ES guideline would have. The guideline recommendations could improve by addition of other obesogenic drugs than antipsychotics, and more elaborate genetic testing instructions.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology