ABSTRAGTLeptin can be regarded as a marker of the nutritional status of the body. This study was performed to determine the correlation of leptin levels with insulin (I) and androgens in girls with premature pubarche (PP) and prepubertal controls (C) with (OB) or without (nOB) obesity. We studied 25 girls with PP and 14 C; girls were dived into two subgroups according to body mass index (BMI): OB (18 PP and 8 C) and nOB (7 PP and 6 C). Obesity was defined as BMI >95 th percentile for chronological age. Serum levels of leptin, I, glucose (G), DHEAS, testosterone, androstenedione (A), Cortisol, SHBG, IGFBP-1 and lipid profile were measured. The fasting G to I ratio (FGIR) was calculated and FGIR <7 was considered as suggestive of I resistance (IR). Data were analyzed comparing PP vs C and OB vs nOB. Serum DHEAS (0.60 ± 0.45 vs 0.18 ± 0.22 μg/ml) and A (895.5 ± 420.4 vs 457.0 ± 352.1 pg/ml) levels were significantly higher in PP than C. Other hormonal and metabolic parameters were similar. Serum leptin (30.8 ± 18.3 vs 8.1 ± 5.9 ng/ml), A (841.8 ± 471.1 vs 522.5 ± 317.2 pg/ml), DHEAS (0.53 ± 0.44 vs 0.31 ± 0.39 pg/ml), G (88.4 ± 8.8 vs 80.2 ± 8.1 mg/dl), I (13.5 ± 7.7 vs 5.1 ± 3.7 μϋ/ml) and total cholesterol (TC) (180.5 ± 30.9 vs 161.8 ± 29.5 mg/dl) levels were greater in the OB than in the nOB group. IR was observed in 10 girls with OB and in one with nOB. Leptin was correlated with BMI (r = 0.83), SHBG (r = -0.44), IGFBP-1 (r = -0.47), I (r = 0.37), A (r = 0.48) and TC (r = 0.36), but in multiple regression analysis only with BMI (r 2 = 0.72, ρ <0.001). Girls with PP and prepubertal OB girls showed elevated leptin levels independent of I and androgen levels. Girls with OB had a greater degree of hyperandrogenism and IR. As obesity, IR and hyperandrogenism are common findings in polycystic ovary syndrome (PCOS), which is more prevalent in young women with a history of PP, a role of leptin in PCOS can be suggested. In addition, girls with PP could be considered a population at risk for plurimetabolic syndrome. KEY WORDSleptin, insulin, androgens, obesity, premature pubarche

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.

The aim of this study was to describe the ovarian structure (OS) and its relationship with hyperandrogenism in girls with premature pubarche (PP). A pelvic ultrasound was carried out in 23 girls with PP and in 57 prepubertal age-matched controls (C), and the OS was subdivided into five classes (c): 1-homogeneous; 2-microcystic, 3-multicystic, 4-polycystic and 5-follicular. In the girls with PP, an ACTH test was performed, and the presence of hormonal levels >3 SD of postpubertal normal levels and not compatible with late-onset congenital adrenal hyperplasia were considered an exaggerated response. The fasting levels of glucose (G) and insulin (I) were measured and the fasting I to G ratio (FIGR) was calculated. FIGR >22 was suggestive of I resistance (IR). The microcystic structure (c2) was more frequently found in the PP than in the C group (63% vs 35%, p=0.03). In the PP group, we observed the following OS: cl (n=6), c2 (n=15), c3 (n=1) and c4 (n=1). 11-Deoxycortisol--both basal and after ACTH--was greater in the PPc2 group than in PPc1 (p=0.04, p=0.0008, respectively). We also observed an exaggerated response to ACTH in 87% of the girls with PP, greater in the PPc2 group than in PPc1 (p=0.04). The FIGR showed IR in 44% of girls with PP, but I levels and FIGR were similar between PPc1 and PPc2. These findings suggest generalized adrenocortical hyperresponsiveness in girls with PP, which is more accentuated in PPc2. Long-term follow-up of girls with PP into adulthood is warranted to ascertain whether microcystic ovarian structure precedes functional ovarian hyperandrogenism.

Realizamos ultra-sonografia pélvica em tempo real e de alta resolução em 140 meninas com idade entre dois e 18 anos, para descrever a prevalência de ovários policísticos durante o desenvolvimento puberal normal. O volume dos ovários foi calculado e sua estrutura classificada como homogênea, microcística, multicística, policística e folicular. O volume aumentou e a freqüência das classes ovarianas variou de acordo com o status puberal. Os ovários eram de aspecto policístico em 8% (duas meninas pré-puberais e nove pós-puberais), com volume normal em 8/11 pacientes. Consideramos que a utilização do volume como critério diagnóstico de ovários policísticos pode ser de difícil interpretação durante este período e enfatizamos a importância da avaliação da ecogenicidade do estroma pelo ultra-som. Uma hipótese atrativa, mas que necessita de confirmação através de estudos longitudinais, é se essas meninas com ovários policísticos na ultra-sonografia serão destinadas, em alguns casos, a tornar-se adultas com a síndrome dos ovários policísticos.

RESUMORealizamos ultra-sonografia (USG) pélvica em tempo real e de alta resolução em 140 meninas normais pré e pós-puberais, entre 2 e 18 anos incompletos, para descrever as mudanças da morfologia e do tamanho do útero e dos ovários com a idade e durante o desenvolvimento puberal. Os volumes do útero (VU) e dos ovários (VO) foram calculados, a morfologia uterina foi descrita como pré-puberal (corpo/colo <1) ou não e a estrutura ovariana foi classificada como homogênea (até 3 cistos < 9mm), microcística (4-10 cistos < 9mm), multicística (+10 cistos < 9mm), policísti-ca (+10 cistos e estroma hiperecogênico) e folicular (pelo menos uma área cística ³ 9mm). Na fase pré-puberal, os volumes do útero e ovários foram de 1,0±0,7cm 3 e 0,9±0,5cm 3 , respectivamente, mas aumentaram com a puberdade. Consideramos como normal pré-puberal os volumes até 2DP da média (VU £ 2,5cm 3 e VO £ 2,0cm3 ) e como sinal de puberdade os volumes maiores que 4DP da média pré-puberal (VU ³ 4cm 3 e VO ³ 3cm 3 ). A morfologia uterina, a presença de eco endometrial e a freqüência das classes ovarianas dependem do status puberal (p<0,005). Os ovários homogêneos foram encontrados somente em pré-puberes (52%); a classe microcística foi a mais comum no início (Tanner II-III, 51%) e a multicística no final da puberdade (Tanner IV-V, 47%); a estrutura policística foi achada em todos os estádios puberais (4-11%) e a folicular (6%) apenas na puberdade. O útero e os ovários aumentam progressivamente durante a infância e a puberdade. O desenvolvimento normal do ovário é contínuo e dinâmico. Ainda não é claro se a presença de ovários policísticos na infância possa representar uma predisposição futura para a síndrome dos ovários policísticos. (Arq Bras Endocrinol Metab 1999;43/3: 210-216) Unitermos: USG pélvica; Critérios de normalidade; Pré-puberal; Pós-puberal. ABSTRACTReal-time ultrasonography of the pelvic organs was performed in 140 healthy girls aged 2-18 years. The aim of this study was to define the volumes and to relate the uterine and ovarian morphological changes to chronological age and the normal pubertal development. Uterine and ovarian volumes (UV and OV) were calculated; uterine morphologic was described as prepubertal (corpus/cervix < 1) or not and the ovarian structure was classified as homogeneous (less than 3 cysts < 9mm), microcystic (4-10 cysts < 9mm), multycystic (+ 10 cysts < 9mm in diameter), polycystic (+ 10 cysts and increased stroma) and follicular (at the least one cystic area > 9mm). Prepubertal UV and OV were 1.0±0.7cm 3 and 0.9+0.5cm 3 , respectively. We considered volumes up to 2SD (UV £ 2.5cm ) as indicators of puberty. Uterine morphology, presence of endometrial echo, and ovarian structure related to sexual development (p<0.005). Homogeneous ovaries were visualized only in prepubertal girls (52%); microcystic class was the most common find-