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Pediatric Endocrinology |
Adolescent and Endocrine Unit (L.I., A.C.) and Hormonal Laboratory (N.P., S.R.), Hospital Universitario Materno-Infantil Vall d’Hebron, Barcelona, Spain; Clinica Pediatrica, University of Parma (M.Z.), Parma, Italy; and the Department of Pediatrics, Albert Einstein College of Medicine/Montefiore Medical Center (P.S.), Bronx, New York 10467
Address all correspondence and requests for reprints to: Lourdes Ibáñez, M.D., Adolescent and Endocrine Unit. Hospital Universitario Materno-Infantil Vall d’Hebron, P° Vall d’Hebron 119–129, 08035 Barcelona, Spain.
The fasting insulin resistance index, mean blood glucose, mean serum insulin (MSI), early insulin response to glucose, glucose uptake rate in peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were evaluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postmenarcheal (B5; n = 16)] and in 86 Tanner stage- and bone age-matched controls. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Body mass indexes did not differ significantly between patients and controls within the same pubertal stage.
MSI levels showed a significant increase with pubertal onset in all subjects, as expected. Patients showed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, respectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake rate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respectively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01, P < 0.05, and P < 0.001, respectively) compared to controls. Among others, significant correlations between SHBG and MSI levels (r = -0.49; P < 0.0001) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were found in all subjects.
Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend strong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The possible causal role of hyperinsulinemia in adrenal and/or ovarian androgen hypersecretion remains to be established.
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L. Ibáñez, C. Valls, N. Potau, M. V. Marcos, and F. de Zegher Sensitization to Insulin in Adolescent Girls to Normalize Hirsutism, Hyperandrogenism, Oligomenorrhea, Dyslipidemia, and Hyperinsulinism after Precocious Pubarche J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3526 - 3530. [Abstract] [Full Text]
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P. Vuguin, B. Linder, R. G. Rosenfeld, P. Saenger, and J. DiMartino-Nardi The Roles of Insulin Sensitivity, Insulin-Like Growth Factor I (IGF-I), and IGF-Binding Protein-1 and -3 in the Hyperandrogenism of African-American and Caribbean Hispanic Girls with Premature Adrenarche J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2037 - 2042. [Abstract] [Full Text]
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L. Ibáñez, N. Potau, I. Francois, and F. de Zegher Precocious Pubarche, Hyperinsulinism, and Ovarian Hyperandrogenism in Girls: Relation to Reduced Fetal Growth J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3558 - 3562. [Abstract] [Full Text]
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S. H. Travers, J. I. Labarta, S. E. Gargosky, R. G. Rosenfeld, B. W. Jeffers, and R. H. Eckel Insulin-Like Growth Factor Binding Protein-I Levels Are Strongly Associated with Insulin Sensitivity and Obesity in Early Pubertal Children J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1935 - 1939. [Abstract] [Full Text]
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