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Insulin Sensitivity and the Insulin-Like Growth Factor System in Prepubertal Boys with Premature Adrenarche

Department of Pediatrics (M.R.D., M.E.S., A.M.M., D.C., L.S.L., C.G., S.E.O.), Division of Pediatric Endocrinology, Columbia University, College of Physicians and Surgeons, New York, New York 10032; Department of Obstetrics and Gynecology (M.F.), Columbia University, New York, New York 10032; and Information Sciences Division (D.J.M.), Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962

Address all correspondence and requests for reprints to: Sharon E. Oberfield, M.D., Columbia University, College of Physicians and Surgeons, Division of Pediatric Endocrinology, 630 West 168th Street, PH 5 East-522, New York, New York 10032. E-mail: seo8{at}columbia.edu.

Abstract

Girls with premature adrenarche (PA), similar to women with polycystic ovarian syndrome, display alterations in the IGF system, may have impaired insulin sensitivity, and demonstrate unfavorable lipid profiles. Girls with PA are also at increased risk for functional ovarian hyperandrogenism. Metabolic studies in boys with PA, however, are limited. The objective of this study was to determine whether boys with PA show alterations in insulin sensitivity and the IGF system. We studied an ethnically heterogeneous group of 19 prepubertal boys: 11 with PA (age, 8.2 ± 0.7 yr; body mass index (BMI)-Z score, 1.8 ± 1.1) and 8 controls (age, 7.9 ± 0.8 yr; BMI-Z score, 1.2 ± 1.0). Fasting levels of glucose, insulin, proinsulin (P₀), hemoglobin A1c, testosterone, SHBG, 4-androstenedione, dehydroepiandrosterone sulfate, LH, FSH, IGF-I, IGF-binding protein-1, IGF-binding protein-3, free IGF-I, and lipids were measured. Ten of 11 boys with PA and six of eight controls underwent standard oral glucose tolerance testing. The insulin response to this test was measured by the insulin area under the curve. Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. All values were adjusted for BMI-Z score. Total IGF-I, P₀, ratio of P₀ and fasting insulin level, and log insulin area under the curve were higher, and SHBG was lower in the boys with PA, compared with controls. Decreased insulin sensitivity was suggested by decreased composite insulin sensitivity index. A trend toward greater triglycerides was observed in the boys with PA, compared with the controls. Prepubertal boys with PA show differences in the IGF system and decreased insulin sensitivity, independent of obesity, as observed in girls with PA. These findings suggest that both boys and girls with PA should be monitored for the development of insulin resistance and associated complications, including diabetes mellitus and cardiovascular disease.

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