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Relative Growth Hormone Deficiency and Cortisol Excess Are Associated with Increased Cardiovascular Risk Markers in Obese Adolescent Girls

Neuroendocrine Unit (M.R., P.T., N.M., K.K.M., A.K., M.M.) and Department of Radiology (M.B.), Massachusetts General Hospital and Harvard Medical School, and Pediatric Endocrine Unit (M.R., M.M.), MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Madhusmita Misra, M.D., M.P.H., Neuroendocrine Unit, Massachusetts General Hospital, BUL 457, Boston, Massachusetts 02114. E-mail: mmisra{at}partners.org.

Context: Obesity in adolescents is increasingly prevalent and its impact on cardiovascular risk important to determine. Hormonal predictors of cardiovascular risk markers in obese adolescents are not known.

Objective: Our objective was to examine whether relative GH deficiency and cortisol excess are determinants of increased cardiovascular risk markers in obese teenage girls.

Design and Setting: A cross-sectional study was conducted at a clinical research center.

Study participants: Thirty girls (15 obese girls and 15 normal-weight controls) 12–18 years old matched for maturity and race.

Main Outcome Measures: Inflammatory markers of cardiovascular risk including high-sensitivity C-reactive protein (hsCRP), TNF- receptors 1 and 2, E-selectin, soluble intercellular adhesion molecule-1, and IL-6 were analyzed. Leptin, adiponectin, and 24-h urine free cortisol (UFC) were also measured. A GHRH-arginine stimulation test was performed.

Results: The hsCRP levels were higher in obese girls than controls (4.63 ± 4.81 vs. 0.67 ± 0.72 mg/liter; P = 0.002 after log conversion), as were other markers of cardiovascular risk. Eight of the 15 obese girls but no normal-weight girl had hsCRP higher than 3 mg/liter (P = 0.002). Body mass index SD score was higher than 4.0 in 87.5% of girls with hsCRP higher than 3 mg/liter and no girls with hsCRP less than 3 mg/liter. Girls with hsCRP higher than 3 mg/liter had higher UFC and lower peak GH compared with those with hsCRP less than 3 mg/liter. Peak GH was an important negative predictor of most markers of increased cardiovascular risk. In addition to peak GH, UFC and adiponectin independently predicted hsCRP.

Conclusion: Relative GH deficiency and cortisol excess are significant contributors to increased levels of markers of cardiovascular risk in obese adolescent girls.

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