HYPERINSULINEMIA IN POSTPUBERTAL GIRLS WITH A HISTORY OF PREMATURE PUBARCHE AND FUNCTIONAL OVARIAN HYPERANDROGENISM

Previous studies have documented the association of insulin resistance and hyperandrogenism in adult women with functional ovarian hyperandr ogenism (FOH) or polycystic ovary syndrome (a form of FOH). However, t he possible impact of adrenal hyperandrogenism development during chil dhood in premature pubarche (PP) patients on postpubertal insulin secr etion patterns remains unclear. The fasting insulin to glucose ratio, C peptide, early insulin response to glucose (IRG), mean blood glucose , mean serum insulin (MSI), glucose uptake rate in peripheral tissues (M), and insulin sensitivity indexes (SI) in response to a standard or al glucose tolerance test were evaluated in 13 PP girls with FOH (grou p A; age, 17.2 +/- 0.5 yr), 11 eumenorrheic nonhirsute PP girls (group B; age, 16.6 +/- 0.5 yr), and 21 age-matched controls (group C). Body mass indexes (BMI) were similar in the 3 groups (group A, 23.3 +/- 0. 8; group B, 22.5 +/- 0.6; group C, 20.6 +/- 0.5 kg/m(2)). MSI values w ere significantly higher in FOH patients than in controls (74.7 +/- 17 .6 vs. 45.7 +/- 4.1 mU/L; P < 0.0l), but were not different from those in group B (63.3 +/- 11.1 mU/L). Thirty-eight percent of FOH patients (group A) and 27% of non-FOH patients (group B), all of whom had norm al BMI, showed MSI levels well above the upper normal limit for contro ls (>83.3 mU/L). MSI correlated with the degree of ovarian hyperandrog enism [defined by an abnormal 17-hydroxyprogesterone response to chall enge with the GnRH analog leuprolide acetate; group A] and with the fr ee androgen index [testosterone (nanomoles per L)/sex hormone-binding globulin (nanomoles per L) x 100; groups A and B)]. Although IRG, gluc ose uptake rate in peripheral tissues, mean blood glucose, and SI valu es were not significantly different in the 3 groups, 3 patients in gro up A and 1 patient in group B showed decreased insulin sensitivity and /or an enhanced early IRG. Among others, significant correlations betw een MSI: and free androgen index values (r = 0.6; P < 0.002; groups A and B) and between BMI and SI(r = -0.53; P < 0.05; groups A and B) wer e found. Peak 17-hydroxyprogesterone responses to ACTH at PP diagnosis correlated positively with SI in both groups of patients (r = 0.53; P < 0.007). Hyperinsulinemia is a common feature in adolescent PP patie nts with FOH and appears to be directly related to the degree of andro gen excess. Long term follow-up of PP patients into adulthood is warra nted to ascertain whether hyperinsulinemia actually precedes FOH devel opment and whether overt insulin resistance ensues.