Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.

Girls with premature adrenarche (PA), similar to women with polycystic ovarian syndrome, display alterations in the IGF system, may have impaired insulin sensitivity, and demonstrate unfavorable lipid profiles. Girls with PA are also at increased risk for functional ovarian hyperandrogenism. Metabolic studies in boys with PA, however, are limited. The objective of this study was to determine whether boys with PA show alterations in insulin sensitivity and the IGF system. We studied an ethnically heterogeneous group of 19 prepubertal boys: 11 with PA (age, 8.2 +/- 0.7 yr; body mass index (BMI)-Z score, 1.8 +/- 1.1) and 8 controls (age, 7.9 +/- 0.8 yr; BMI-Z score, 1.2 +/- 1.0). Fasting levels of glucose, insulin, proinsulin (P(0)), hemoglobin A1c, testosterone, SHBG, delta4-androstenedione, dehydroepiandrosterone sulfate, LH, FSH, IGF-I, IGF-binding protein-1, IGF-binding protein-3, free IGF-I, and lipids were measured. Ten of 11 boys with PA and six of eight controls underwent standard oral glucose tolerance testing. The insulin response to this test was measured by the insulin area under the curve. Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. All values were adjusted for BMI-Z score. Total IGF-I, P(0), ratio of P(0) and fasting insulin level, and log insulin area under the curve were higher, and SHBG was lower in the boys with PA, compared with controls. Decreased insulin sensitivity was suggested by decreased composite insulin sensitivity index. A trend toward greater triglycerides was observed in the boys with PA, compared with the controls. Prepubertal boys with PA show differences in the IGF system and decreased insulin sensitivity, independent of obesity, as observed in girls with PA. These findings suggest that both boys and girls with PA should be monitored for the development of insulin resistance and associated complications, including diabetes mellitus and cardiovascular disease.

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.

In adults with impaired glucose tolerance (IGT) and obesity (OB), an elevated proinsulin (PI) is predictive of type 2 diabetes mellitus (DM) and precedes the diagnosis by 5-20 yr. In type 2 DM, the PI is disproportionately elevated, i.e. increased PI/insulin ratio (PI/I). Few studies have evaluated PI in children at risk for type 2 DM. In the face of the current epidemic, we evaluated the relationship of PI and PI/I to IGT, insulin resistance (IR) defined by homeostasis model of assessment (HOMA), degree of OB, and stage of puberty in 70 girls (mean age 10.8 yr; body mass index z-score 3.5; ethnicity 64% Hispanic, 19% white, 16% African-American, and 1% other). Family history of DM was reported in 83%, and acanthosis nigricans was present in 80%. Subjects underwent a 2-h oral glucose tolerance test with glucose, insulin, and PI determinations every 30 min. All had normal hemoglobin A1c and fasting glucose. Five had IGT. With higher HOMA-IR, PI increased (P < 0.05), yet the ratio of fasting PI/I was lower (P < 0.05). Girls with body mass index z-score greater than 4 (n = 29) had higher PI than nonobese girls (n = 19, P < 0.05), but PI/I ratios were not different. PI-0 was increased in late puberty (n = 29), compared with prepuberty (n = 26, P < 0.05), but PI/I ratios showed no statistical difference. We found PI increased with increasing IR and OB in girls. Overall, PI/I was not different, suggesting the elevated PI reflects increased beta-cell output proportional to the elevated insulin in these groups and not a defect in PI processing or secretion. In fact, the lower fasting PI/I of the highest HOMA-IR quartile vs. the lowest HOMA quartile indicates more efficient conversion of PI to I in the presence of increasing IR in these girls.

This study was conducted to evaluate variations in and the prevalence of the lingual concavity. Images were taken between January 1, 2011, and August 31, 2015, from a total of 104 patient charts randomly selected from a private practice. These images were acquired from a single cone beam computerized tomography (CBCT) machine. The CBCTs were reviewed in cross-sectional images in both the left and right anterior incisor and posterior molar regions. These scans were classified into 1 of 3 categories-parallel, concave, or convex-based on the measurements of the level of concavity degree as well as the mandibular morphology observed. Lingual concavity characteristics including depth, angulation, and vertical location were also measured. Most of the posterior mandibular CBCT scans were classified as concave. Although there was no significant difference detected for race or gender, statistical significance was noted with regard to age, with an increase in prevalence observed at age 63 years and older. Of the 3 different morphological classifications used, the vast majority were identified as concave in the posterior mandibular regions and parallel in the anterior mandibular region. There was a significant decrease in concavity VL/height (bone loss) associated with age, which was most commonly seen in edentulous areas.