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Elevated Free IGF-I Levels in Prepubertal Hispanic Girls with Premature Adrenarche: Relationship with Hyperandrogenism and Insulin Sensitivity

Division of Pediatric Endocrinology (M.E.S., A.M.M., L.S.L., S.E.O.), Department of Obstetrics and Gynecology (M.F.), Columbia University, New York, New York 10032; and Nathan Kline Institute (D.J.M.), Orangeburg, New York 10962

Address all correspondence and requests for reprints to: Sharon E. Oberfield, M.D., 630 West 168th Street, PH-5E-522, New York, New York 10032. E-mail: seo8{at}columbia.edu

Girls with premature adrenarche (PA) (the onset of pubic hair before the age of 8 yr associated with elevated levels of adrenal androgens and no evidence of true puberty or adrenal dysfunction) may be at increased risk for development of polycystic ovarian syndrome (PCOS). Alterations in the IGF system, including elevated free IGF-I, have been demonstrated in PCOS and may be involved in its pathogenesis. Hyperinsulinemia, elevated total IGF-I, and decreased IGF-binding protein-1 (IGFBP-1) have also been reported in PA. Dysregulation of the IGF system may be involved in the pathogenesis of PA and its progression to PCOS.

We compared the insulin/IGF system in 17 prepubertal girls with PA and nine prepubertal controls. Both groups were predominantly obese. Total and free IGF-I were elevated in the premature adrenarche group. No differences in basal insulin, insulin area under the curve in response to an oral glucose tolerance test, or IGFBP-1 were noted. These effects persisted when adjusted for adiposity using body mass index-Z score. Total and free IGF-I were positively correlated, and IGFBP-1 was negatively correlated with 4-androstenedione, but not with dehydroepiandrosterone sulfate. Free IGF-I trended toward higher levels in the insulin-resistant subgroup, compared with the insulin-sensitive subgroup.

These results suggest altered regulation of the insulin/IGF system in prepubertal girls with PA and a possible role for free IGF-I in the pathogenesis of the hyperandrogenism of PA as well as its progression to PCOS.

This work was supported in part by grants from the NIH (RR00645), Genentech, Inc., Eli Lilly & Company, and Pharmacia & Upjohn. This work was presented in part at the Lawson Wilkins Pediatric Endocrine Society Meeting in Montreal, Canada, July 2001.

Abbreviations: 4-A, 4-Androstenedione; BMI, body mass index; FGIR, fasting glucose to insulin ratio; GTT, glucose tolerance test; IGFBP-1, IGF binding protein-1; IR, insulin resistant; IS, insulin sensitive; OGTT, oral GTT; PA, premature adrenarche; PCOS, polycystic ovarian syndrome; QUICKI, quantitative insulin sensitivity check index.

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