The aim of this study was to determine serum
insulin,
insulin-like growth factor-I (
IGF-I) and its
binding proteins (IGFBP-1 and IGFBP-3) levels and their relationship with
androgen levels and ovarian structure in 23 girls with premature pubarche (PP). Fasting levels of
testosterone,
dehydroepiandrosterone (
DHEA) and its
sulfate (DHEAS),
androstenedione (delta4A),
sex hormone binding globulin (SHBG),
glucose (G),
insulin (I),
IGF-I,
IGFBP-1,
IGFBP-3 were measured.
Androgens or
steroid hormone levels > 3 SD of normal postpubertal levels were considered as an exaggerated response to the
ACTH test. The fasting I to G ratio (FIGR) was calculated and FIGR > 22 was suggestive of
insulin resistance (IR). A pelvic ultrasound (US) was carried out and the ovarian structure was divided into five classes (c): c1--homogeneous, c2--microcystic, c3--multicystic, c4--polycystic and c5--follicular. The girls with PP were divided into two groups according to the main ovarian classes observed: PPc1 (n = 6) and PPc2 (n = 15). The FIGR showed IR in 44% of patients. The
androgens, SHBG, G, I, FIGR,
IGF-I and
IGFBP-1 levels were similar among the groups (PPc1 vs PPc2). An exaggerated response to
ACTH was more common and
IGFBP-3 levels were higher in the PPc2 than in the PPc1 group (p = 0.04). Regression analysis revealed that I was correlated with DHEAS (r = -0.43, p = 0.04) and
IGFBP-1 (r = -0.51, p = 0.01);
IGF-I was correlated with
DHEA (r = -0.42, p = 0.05), delta4A (r = -0.47, p = 0.02), SHBG (r = -0.43, p = 0.04),
IGFBP-1 (r = -0.61, p = 0.002) and
IGFBP-3 (r = 0.56, p = 0.005);
IGFBP-1 was correlated with SHBG (r = 0.56, p = 0.005). These findings suggest that there might be interactions between the
insulin-
IGF-I-IGFBPs system and
hyperandrogenism. However, the possible causal role of adrenal
androgen hypersecretion on the
insulin-
IGF-I-IGFBPs axis and ovarian structure in girls with PP remains to be established. Since studies reveal that
IGFBP-3 levels could be a negative predictor for
insulin sensitivity throughout puberty, we hypothesize that girls with PP and microcystic ovaries are at risk of developing IR in the course of normal puberty.