June 3, 2024
Pediatric Research Update | Treatment of Hypothalamic Obesity
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Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s update addresses treatment of hypothalamic obesity.
Treatment of Hypothalamic Obesity in People with Hypothalamic Injury: New Drugs are on the Horizon #
Article Summary
Hypothalamic obesity (HO) is a complex disorder resulting from either monogenic cause or injury of the hypothalamus. Lifestyle intervention alone is usually ineffective. This article aims to discuss newer treatments for HO.
Article Review
The article addresses the complex condition of hypothalamic obesity (HO). It briefly discusses the two types of HO which are genetic or acquired. The authors primarily concentrate on acquired HO, which arises from hypothalamic lesion often treated through surgery and/ or radiation. Craniopharyngioma (CP) is identified as the most prevalent cause of acquired HO.
In discussing the pathophysiology and phenotypes of acquired HO, the authors describe a syndrome characterized by excessive weight gain resulting from hyperphagia potentially due to leptin resistance and deficiencies in downstream energy regulation neuroendocrine pathway. Additional features include decreased sympathetic activity, low energy expenditure, temperature dysregulation, and increased energy storage in adipose tissue, all of which are very similar in patients with monogenic cause of HO.
The article highlights the lack of FDA approved treatment specifically for HO but reviews existing medications currently approved for general obesity such as GLP-1 receptor agonists (GLP1Ras) and combination Phentermine/ Topiramate. It also mentions drugs that had undergone clinical trials for HO including oxytocin and Tesofensine. Currently, Setmelanotide, a MC4R agonist approved for certain monogenic obesity forms is undergoing clinical trials for acquired HO.
As obesity pharmacotherapy is rapidly evolving, the development of newer drugs is anticipated. Tirzepitide, approved for adult Type 2 diabetes, has demonstrated 20% weight loss, while Retatrutide, a triple agonist (GIP, GLP and glucagon) is currently in a phase 2 clinical trial showing 24.2% weight loss over 48 weeks.
Treatment for HO should be tailored based on phenotype spectrum as previously discussed, recommending a switch to another drug or combination therapy if there is no response after three months.
As a final statement, authors propose that MC4R agonism could represent a new standard of treatment for HO.
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Roth CL, Zenno A. Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon. Front Endocrinol (Lausanne). 2023 Sep 13;14:1256514. doi: 10.3389/fendo.2023.1256514. PMID: 37780616; PMCID: PMC10533996.
Article reviewed by:
Jacqueline T. Chan, MD, FAAP, DABOM
Dr. Jacqueline Chan completed her Pediatric residency at Sinai Children's Hospital, and her Pediatric endocrinology Fellowship at University Of Illinois Chicago/ Rush University.
Dr. Chan is certified in Pediatrics, Pediatric Endocrinology and Obesity Medicine. She was an assistant professor of pediatrics faculty at the Children’s hospital of Georgia for 5 years. She has provided multiple education lecture series and podcasts about various endocrine and metabolic issues. In addition, she has published multiple peer reviewed articles and is an active member of the Obesity Medicine Association Pediatric Committee.
Dr. Chan is currently an Assistant Professor of Pediatrics at the University of Utah and is in the Division of Pediatric Endocrinology at Primary Children´s Medical Center where Dr. Chan and is leading a multidisciplinary team for children with obesity. Her interest is on comorbidities associated with pediatric obesity mainly Type 2 diabetes and lipid disorders, as well as Hypothalamic obesity.
Pediatric Research Update: Change in Weight Status from Childhood to Young Adulthood and Risk of Adult Coronary Heart Disease
Article Summary This long-term population study examines how changes in weight from childhood to young adulthood relate to adult coronary heart disease risk, highlighting adolescence as a critical period. The BMI Epidemiology Study (BEST) in Gothenburg, Sweden examined whether changes in weight status from childhood through young adulthood influence adult CHD risk. Childhood and Young Adulthood Overweight, Including Obesity, and the Risk of CHD: Both childhood overweight and young adult overweight/obesity were associated with higher adult CHD risk, though no significant differences were seen between sexes. Changes in Weight Status Between Childhood and Young Adulthood and the Risk of CHD: Individuals who were overweight in childhood but normalized by young adulthood had CHD risk like those who were never overweight, indicating reversibility of risk. In contrast, pubertal onset overweight (normal childhood weight but overweight in young adulthood) and persistent overweight (overweight in both periods) were linked to higher CHD risk, with pubertal onset overweight carrying the highest risk, particularly in men. BMI Percentile Changes Between Childhood and Young Adulthood and the Risk of CHD: Using BMI percentiles, high childhood BMI that normalized by young adulthood did not increase CHD risk, while high young adult BMI, regardless of childhood BMI, was linked to higher CHD risk. While excess adiposity in childhood is associated with later obesity, it does not appear to irreversibly program CHD risk if weight normalizes by young adulthood. Change in Weight Status From Childhood to Young Adulthood and Risk of Adult Coronary Heart Disease.
Pediatric Research Update: Shifts in US Pediatric Obesity Treatment After the AAP Guidelines
A recent study by Rodriguez et al. (2025) reviewed differences in pediatric obesity treatment before and after the release of the 2023 AAP Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents with Obesity.
Pediatric Research Update: Consensus Statement on Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) in Children and Adolescents
Pediatric MASLD is rapidly rising alongside childhood obesity. This expert consensus outlines current evidence on epidemiology, diagnosis, and management, highlighting screening strategies and emerging therapies to guide early identification and care.