Girls with PA (pubic hair before 8 yrs) can progress to functional ovarian hyperandrogenism(FOH) or Polycystic Ovaries (PCO). We reported that many B/H girls with PA have an exaggerated ACTH stimulated 17OH Pregnenolone (s17OH Preg) response to ACTH and an elevated ratio of 17OH Preg/17OH Progesterone(17OH Prog), a pattern described in PCO. The etiology is not known. Alterations of SI and growth factors contribute to the HA of PCO. We evaluated the role of SI using the FSIVGTT(frequently sampled IVGTT) and fasting levels of IGFBP-1 and 3 in 21 prepubertal B/H girls with PA. All patients had a 60 min ACTH test and LHRH test. Results: 11 girls had a nl SI (Gr I); 10 girls (Gr II) had an SI more than 2SD below the mean of normal prepubertal girls (6.57±0.45). Gr II girls with the low SI had the more advanced bone age(BA), higher body mass index (BMI), higher basal insulin(bINS), and higher s17OH Preg. Results are for group I vs. Group II (mean±SD). Table SI correlated inversely with basal 17OH Preg (r=-0.44; p<0.05), with s17OH Preg(I=-0.46;p<0.025), and with ACTH stim. ratio of 17 OH Preg/17OH Prog(I=-0.5, p<0.025). Preliminary data shows all patients had nl IGFBP-3 levels and low/nl levels of IGFBP-1.
Summary: Just as in many women with PCO, the H/A of prepubertal B/H girls with PA can be associated with hyperinsulinism stemming from reduced SI. Possibly, the decreased IGFBP-1 increases the availability of IGF-1, which can then directly stimulate ovarian and adrenal steroidogenesis. This suggests a primary role of altered SI and IGFBP-1 levels in the pathogenesis of PA in B/H girls which may progress to PCO.
