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

Abstract

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 Delta4-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.

Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry

“…[5][6][7]17,18 There is a notable female preponderance in EA and it has been suggested that affected boys may simply exhibit a variant of normal development. [5][6][7]17,18 There is a notable female preponderance in EA and it has been suggested that affected boys may simply exhibit a variant of normal development.…”

Body Composition in Premature Adrenarche by Structural MRI, 'H MRS and DXA

“…It has been suggested that insulin may play a permissive role, and girls with premature adrenarche have been documented with circulating markers of insulin resistance, including hyperinsulinism, decreased IGFBP-1, increased IGF-I and increased PAI-12,3,5,7,8. In earlier studies of girls with PA, elevated concentrations of plasma triglycerides were found compared with controls14,15.…”

“…Metabolic abnormalities reported in prepubertal PA include decreased insulin sensitivity and IGFBP-1, hyperinsulinism, and increased free IGF-I and plasminogen activator inhibitor-1 (PAI-1)2,3,5,7,8. To date, only PAI-1 concentrations have been shown to predict progression to PCOS in a small subgroup of prepubertal girls with PA8.…”

Adolescence and polycystic ovary syndrome: current concepts on diagnosis and treatment

“…The less prepubertal height gain is usually compensated by more pubertal growth, however; in girls who have experienced LBW followed by rapid catch‐up growth in infancy, this compensatory mechanism fails and there is a higher secretion of suprarenal androgens . As it was concluded in the First Latin‐American Consensus of PCOS , among the factors contributing to PP, it has been reported: 1 – altered androgen receptor gene CAG repeat polymorphism ; 2 – increased methylation of androgen receptor ; 3 – increased levels of insulin and insulin growth factors ; 4 – decreased insulin sensitivity during prepubertal and pubertal stages ; 5 – reduced aromatase activity as a consequence of the CYP19 gene variation and 6 – alterations in other genes involved is steroidogenesis, such as 21‐hydroxylase, 3‐beta‐hydroxysteroid dehydrogenase type 2, 5‐alpha reductase and 11‐beta‐hydroxysteroid dehydrogenase .…”