Researchers at Children's Hospital Los Angeles have demonstrated that adolescents and young adults with congenital adrenal hyperplasia (CAH) have significantly increased amounts of abdominal fat tissue, placing them at greater risk for harmful conditions linked to obesity, including cardiovascular disease (CVD).
Their study, which reveals new information about the role of abdominal fat in patients with CAH and points to a need for targeted prevention and therapeutics to avoid these adverse effects, will be published online June 10, 2015 by The Journal of Clinical Endocrinology & Metabolism.
"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 an inherited disorder that affects the adrenal glands, causing the production of excess male sex hormones called androgens. Studies have suggested that the hormonal imbalances inherent to CAH, as well as treatments for the disease - including life-long glucocorticoid therapy to suppress adrenal androgen production - are likely contributors to obesity and CVD risk in these patients.
Over the past two decades, there has been an increasing focus on specific types of fat accumulation in obese individuals. Visceral adipose tissue, accumulated around the body's organs, is of particular concern, because it is highly inflamed in individuals with metabolic syndrome and may produce inflammatory substances associated with CVD. The research team used computed tomography (CT) imaging to quantify specific deposits of both visceral and subcutaneous adipose tissue, the latter found directly below the skin. They also measured metabolic and inflammatory markers, to find out more about the metabolic role of abdominal adipose tissue in patients with CAH.
In addition to increased abdominal fat, they found a higher proportion of pro-inflammatory visceral adipose tissue than of subcutaneous fat in these patients.
Kim explained that increased abdominal fat tissue in CAH is associated with insulin resistance and metabolic syndrome; cell signaling proteins that can stimulate regions of the brain regulating 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."
Additional contributors include Anna Ryabets-Lienhard, DO, Anh Dao-Tran, MPH, Steven D. Mittelman, MD, PhD, Vicente Gilsanz, MD, PhD, Sheree M. Schrager, PhD, and Mitchell E. Geffner, MD, all of Children's Hospital Los Angeles. The research study was supported by the NIH grants KL2TR000131 and 1UL1RR031986; and The Abell Foundation.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's hospital on the West Coast and among the top five in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children's Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California.