Impact Story • Success Story
Hormonal Disorder Tied to Brain Changes That May Drive Childhood Obesity
By Mimi S. Kim(1), et al.
All Authors and Affiliations
Affiliations:
1. Children's Hospital of Los Angeles
2. University of Southern California
Posted April 23, 2026
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Children's Hospital of Los Angeles
Hormonal Disorder Tied to Brain Changes That May Drive Childhood Obesity
Photo by: Southern California CTSI
Abstract
Introduction: Patients with classical congenital adrenal hyperplasia (CAH) exhibit an increased prevalence of obesity from childhood including central adiposity and inflammation. There is also an emerging affected brain phenotype in CAH, with decreased cortico-limbic gray matter volumes and white matter abnormalities. We aimed to study the relationship between brain structure, obesity, and inflammation in children and adolescents with CAH compared to controls. Methods: 27 CAH (12.6 ± 3.4 y, 16 females) and 35 control (13.0 ± 2.8 y, 20 females) participants had MRI of gray matter regions of interest (prefrontal cortex [PFC], amygdala, hippocampus) and white matter microstructure (fornix, stria terminalis [ST]). Anthropometric measures and lab analytes were obtained. Relaimpo analyses (relative importance for linear regression; percent variance) identified which brain structures were most different between groups. Subsequent regressions further quantified the magnitude and direction of these relationships. Correlations analyzed relationships between brain structure, obesity, and inflammation in the context of CAH status. Results: PFC (13.3% variance) and its superior frontal (SF) subregion (14%) were most different between CAH and controls for gray matter; ST (16%) for white matter. Patients with CAH had lower caudal middle frontal (? = -0.56 [-0.96, -0.15]) and superior frontal (? = -0.58 [-0.92, -0.25]) subregion volumes, increased orientation dispersion index in the fornix (? = 0.56 [0.01, 1.10]) and ST (? = 0.85 [0.34, 1.36]), and decreased fractional anisotropy in the fornix (? = -0.91 [-1.42, -0.42]) and ST (? = -0.83 [-1.34, -0.33]) (all p’s < 0.05) indicating axonal disorganization, reduced myelin content, and/or higher microglial density within the affected white matter tracts. For the full cohort, SF was correlated with MCP-1 (r = -0.41), visceral adipose tissue (r = -0.25), and waist-to-height ratio (r = -0.27, all p’s < 0.05); ST was correlated with MCP-1 (r = 0.31) and TNF-? (r = 0.29, all p’s < 0.05); however, after adjusting for CAH status, almost all correlations were attenuated for significance. Conclusions: Relationships among key brain structures, body composition, and inflammatory markers in pediatric patients with CAH could be largely driven by having CAH, with implications for obesity and neuroinflammation in this high-risk population.
Impact Story
Children with a rare hormonal disorder known as congenital adrenal hyperplasia (CAH) often struggle with several complications, including obesity.
A prospective cross-sectional study initiated by researchers at Children’s Hospital Los Angeles (CHLA) examined how brain structure, body fat, and inflammation are connected in children and teens with CAH compared to kids without the disorder. The researchers found that CAH—affecting roughly 1 in 15,000 births—appear to be linked to changes in brain development that may lead to obesity. Genetic differences in hormone pathways appear to shape the brain, influencing how a person with CAH can manage impulses, such as control over food choices.
“Obesity begins at a very young age in a significant number of these patients, especially the more severely affected, and then it’s a lifelong struggle from childhood through adulthood,” said Mimi Kim, MD, MSc, Associate Professor of Clinical Pediatrics at the Keck School of Medicine of the University of Southern California (USC) and CHLA.
The researchers used brain imaging to study 27 children and adolescents with CAH and 35 without. The average participant’s age was 13 years old. They ran MRIs to examine specific brain regions, and measured body fat and inflammation levels in the blood. The team focused on gray matter, which includes areas of the brain like the prefrontal cortex, amygdala, and hippocampus, and white matter pathways, which help areas of the brain communicate. The study appeared in Hormone Research in Paediatrics, the official journal of the Pediatric Endocrine Society.
“Dr. Kim was focused on the obesity phenotypes and the inflammatory phenotypes that she kept seeing in her patients,” said co-author Megan Herting, PhD, Associate Professor of Population and Public Health Sciences at the Keck School of Medicine of USC. “I brought expertise in neuroscience, and together, we applied advanced neuroimaging techniques so we could measure what’s happening at the brain level.”
Trevor Pickering, PhD, a co-author and member of the Biostatistics Epidemiology and Research Design (BERD) team at the Southern California Clinical and Translational Science Institute (SC CTSI), helped design the study and guided the team through the process of analyzing the data.
Brain imaging showed that young people with CAH had smaller volumes in parts of the prefrontal cortex, the region of the brain involved in decision-making and emotional control. They also had signs of disorganized white matter, the brain’s communication highways, which may mean lower quality or damaged brain connections. In addition, the study revealed higher levels of belly fat and inflammatory markers in the blood among the CAH group.
Similar brain changes were observed across all children with higher inflammation or obesity. These associations, however, weakened after accounting for CAH diagnosis, suggesting that obesity is directly linked to the hormonal disorder.
This research demonstrates the importance of interdisciplinary team science in complex medical research. A neuroscientist (Herting) and a physician (Kim) combined their expertise to understand CAH better. The collaboration demonstrates that bringing different perspectives can unlock deeper insights into rare diseases.
Kim is a past recipient of the KL2 Mentored Career Development award from SC CTSI and collaborated with BERD staff as a National Institutes of Health K23 and R03 awardee.
Pickering from SC CTSI’s BERD group helped the research team navigate complex data analysis, particularly with a small patient sample size.
“Having funding to involve a biostatistician early in the research process allows for more comprehensive and nuanced analysis,” Kim added. “Trevor was involved from the early stages of data collection, helping the team strategically select the most important variables and use advanced statistical techniques. His ability to quickly grasp clinical variables and work through intricate study components was instrumental in transforming raw data into meaningful insights.”
This study could help scientists understand obesity better by showing how brain structure can affect eating behaviors and weight gain. Hormones are powerful managers of how our brain grows and works, and studying young people with unique conditions can teach researchers about how brains normally develop.
“If we can understand why patients are developing obesity, we can try to tailor treatments,” said Kim.
The findings highlight the need for more comprehensive care in children with CAH, including strategies that address both metabolic and neurological health. But larger, longer-term studies are needed.
“CHLA is a top West Coast referral hospital for this rare condition, and there are other centers across the country,” Herting said. “We would like to combine forces with other centers to study a larger group of kids as they develop.”
