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Hyperinsulinemia and Decreased Insulin-Like Growth Factor-Binding Protein-1 Are Common Features in Prepubertal and Pubertal Girls with a History of Premature Pubarche1
Abstract
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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“Morning 17-OHP values >200 ng/dl appear to detect most adult women with NCAH [108,109]”
From The Diagnosis of Polycystic Ovary Syndrome during Adolescence (2015) · cites this paper as [108]
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Metadata
- Authors
- Ibáñez, L., Potau, N., Zampolli, M., RiquÉ, S., Saenger, P., & Carrascosa, A.
- Affiliations
- Adolescent and Endocrine Unit (L.I., A.C.), Barcelona, Spain;
- Vall d'Hebron Hospital Universitari (ES)
- University of Parma (IT)
- Hormonal Laboratory (N.P., S.R.), Hospital Universitario Materno-Infantil Vall d’Hebron, Barcelona, Spain;
- Albert Einstein College of Medicine (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-07-01
- Volume
- 82
- Issue
- 7
- Pages
- 2283-2288
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2009295157
- Cited by
- 199
- References
- 49
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 6 · 2012: 1
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- premature pubarche, hyperinsulinemia, insulin resistance, IGFBP-1, insulin-like growth factor I, sex hormone-binding globulin, free androgen index, pubertal development, prepubertal girls, insulin sensitivity, glucose uptake, insulin response to glucose, sex hormones, polycystic ovary syndrome
- MeSH terms
- Adolescent, Child, Child, Preschool, Female, Humans, Hyperinsulinism, Insulin, Insulin-Like Growth Factor I, Menarche, Puberty, Sex Hormone-Binding Globulin, Body Mass Index, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3
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