In a recent study published in the Journal of Clinical Endocrinology & Metabolism, a team of researchers at Children’s Hospital Los Angeles found that adolescents and young adults with congenital adrenal hyperplasia (CAH) have significantly increased amounts of abdominal fat tissue, placing them at higher risk for harmful diseases associated with obesity, such as cardiovascular disease (CVD).
The study titled “Increased Abdominal Adiposity in Adolescents and Young Adults With Classical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency“ adds more evidence about the role of visceral adipose tissue (VAT) in patients with CAH and points to a need for targeted prevention and therapeutics to prevent these adverse effects.
“We see an increased prevalence of obesity in adolescents with CAH, even above the alarmingly high rates already seen in children,” said principal investigator Mimi S. Kim, MD, co-director of the Congenital Adrenal Hyperplasia Clinic of the Division of Endocrinology at CHLA. “We also see that these young patients have a more unfavorable abdominal fat distribution, which could actively promote cardiovascular disease.”
CAH is a hereditary condition affecting the adrenal glands and causing the production of excess male sex hormones called androgens. Evidence indicates that the hormonal imbalances inherent to CAH, as well as treatments for the disease – such as life-long glucocorticoid therapy to suppress adrenal androgen production — are contributors to obesity and CVD risk in these patients.
Circulating concentrations of adipokines such as leptin are abnormally elevated in both CAH and obese individuals and are important in the modulation of food intake, insulin sensitivity, and energy homeostasis.
To determine whether adolescents and young adults with classical CAH had more VAT and sc adipose tissue (SAT) than matched controls and whether VAT and SAT were associated with biomarkers of metabolic syndrome, inflammation, and hyperandrogenism in CAH, the team of researchers included CAH subjects (n 28; 15.6 3.2 y; 15 females) and a group of healthy controls (n 28; 16.7 2.3 y; 15 females) in their study.
The researchers used computed tomography imaging and serum biomarkers associated with CVD risk to measure VAT and SAT.
Results revealed that both VAT and SAT were higher in CAH subjects than controls. The VAT to SAT ratio was also higher in CAH subjects than controls. Within CAH, measures of obesity (waist to height ratio, fat mass) and inflammation (plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, leptin) correlated strongly with VAT and SAT. In addition, homeostasis model assessment of insulin resistance, and low-density lipoprotein correlated with abdominal adiposity.
Kim said that increased abdominal fat tissue in CAH is linked with metabolic syndrome and insulin resistance; cell signaling proteins that can trigger brain regions that regulate appetite and inflammation.
“Inflammation is a risk factor for cardiovascular disease in itself,” added Kim, who is also an investigator with The Saban Research Institute and assistant professor of Clinical Pediatrics in the Keck School of Medicine of the University of Southern California. “It is possible that adolescents and young adults with CAH have systemic low-grade inflammation similar to that found in obese individuals without the disorder.”