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Growth Hormone Deficiency by Growth Hormone Releasing Hormone-Arginine Testing Criteria Predicts Increased Cardiovascular Risk Markers in Normal Young Overweight and Obese Women

Neuroendocrine Unit (A.L.U., A.Y., K.K.M.) and Department of Cardiology (L.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kkmiller{at}partners.org.

Context: Little is known about the relationship between GH and cardiovascular risk markers in women without organic hypothalamic/pituitary disease.

Objective: The objective of the study was to determine whether healthy young overweight and obese women, who would be classified as having GH deficiency (GHD) based on standard criteria used in hypopituitarism (peak GH after stimulation with GHRH and arginine < 5 ng/ml), have increased cardiovascular risk markers.

Design: This was a cross-sectional study.

Setting: The study was conducted at the General Clinical Research Center.

Study Participants: Forty-five women of reproductive age, mean age 33.1 ± 1.2 yr and mean body mass index (BMI) 30.9 ± 1.0 kg/m².

Intervention: There was no intervention.

Main Outcome Measures: Measures included carotid intima-medial thickness, high-sensitivity C-reactive protein (hsCRP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, E-selectin, soluble intercellular adhesion molecule-1, TNF- receptor I, TNF- receptor II, fasting insulin levels, and oral glucose tolerance testing.

Results: Twenty-six percent of overweight or obese subjects and none with BMI less than 25 kg/m² met criteria for GHD. Subjects who met GHD criteria had a mean BMI of 37.0 ± 1.7 kg/m² (range 28.6–43.6 kg/m²), and their mean waist circumference (110.1 ± 3.5 cm) was higher than in overweight/obese women with GH sufficiency (P = 0.007). Mean carotid intima-media thickness, hsCRP, soluble intercellular adhesion molecule-1, TNF- receptor I, and TNF- receptor II levels were higher, and HDL lower, in women meeting GHD criteria than in GH sufficiency. Differences in HDL, hsCRP, and TNF- receptor II remained after controlling for age plus BMI, waist circumference, or trunk fat. There were no differences in measures of insulin resistance.

Conclusions: There may be a relative GHD syndrome in overweight and obese women without organic pituitary or hypothalamic disease that confers increased cardiovascular risk, independent of weight.

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