Abstract
Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment. To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center. This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients. The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort. To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.
Highlights
The diagnostic workup was completed in n = 282 patients
Patients with genetic obesity with intellectual disability (ID) more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005)
Patients with cerebral and medication-induced obesities had lower height-standard deviation scores (SDS) than the rest of the cohort. This is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity
Summary
Obesity is a multifactorial disease that has become one of the greatest health challenges of our time. [1] The prevalence of severe obesity in children and adolescents (as defined by the World Health Organization [2] and the International Obesity Task Force [3]; IOTF) was recently shown to range from 1.7% to 6.3% in several countries. [4] Body mass index is strongly influenced by genetic susceptibility with an estimated heritability of 40–70%. [5, 6] Most children and adolescents with obesity do not have singular underlying medical disorders causing their obesity, such as endocrine disorders, genetic obesity disorders, cerebral or medication-related causes. [7] The pathophysiologic mechanisms of the underlying medical conditions causing obesity are widely varied, leading to the suggestion to talk about “different diseases causing obesity” or “obesities”. [8] Establishing an underlying diagnosis can give insight into the clinical course of the obesity, and lead to tailored monitoring and treatment. [9] In addition, it ends the diagnostic odyssey and can reduce the stigma that patients are confronted with. [10, 11] Since pharmacological treatment for patients with genetic defects affecting the leptin-melanocortin pathway (the hypothalamic system that controls appetite and energy expenditure) [11] is currently being evaluated in clinical trials, identifying these diseases becomes even more relevant. [8, 12] It is difficult to assess which patients should be evaluated for underlying causes. [5, 6] Most children and adolescents with obesity do not have singular underlying medical disorders causing their obesity, such as endocrine disorders, genetic obesity disorders, cerebral or medication-related causes. The current international clinical practice guideline for the evaluation and treatment of pediatric patients with obesity was published in 2017 by the Endocrine Society (ES). Our diagnostic approach included broad evaluation for each patient of all possible underlying medical causes of obesity as mentioned in the ES guideline: endocrine and genetic disorders, as well as cerebral injury and medication use. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited Identifying these causes is vital for patient-tailored treatment
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