Presentation of 493 consecutive girls with idiopathic central precocious puberty: a single-center study.

BACKGROUND: Despite the number of reported data concerning idiopathic central precocious puberty (CPP) in girls, major questions remain including its diagnosis, factors, and indications of gonadotropin releasing hormone (GnRH) analog treatment. METHODS: A retrospective, single-center study was carried out on 493 girls with CPP. RESULTS: Eleven girls (2.2%) were aged less than 3 years. Breast development was either isolated (Group 0, n = 99), or associated with one sign, pubic hair development, growth rate greater than 2 standard deviation score (SDS) or bone age (BA) >2 years above chronological age, (Group 1, n = 187), two signs (Group 2, n = 142) or three signs (Group 3, n = 65). The interval between onset of puberty and evaluation, body mass index (BMI) SDS, plasma luteinising hormone (LH) concentrations (basal and peak) and LH/ follicle-stimulating hormone (FSH) peak ratio after GnRH test, plasma estradiol and uterus length were significantly greater in Groups 2 and 3 than in Groups 0 and 1 respectively. 211 (42.8%) patients were obese and/or had excessive weight gain during the year before puberty. Obese girls more often had BA advance of >2 years (p = 0.0004) and pubic hair development (p = 0.003) than the others. BMI did not correlate with LH or with LH/FSH peak ratio. Girls with familial history of early puberty (41.4%) had greater frequencies of pubertal LH/FSH peak ratios (p = 0.02) than the others. During the 31 years of the study, there was no increase in the frequency of CPP or variation in its characteristics. CONCLUSION: Obesity is associated with a higher BA advance and higher frequency of pubic or axillary hair development but not with LH secretion, suggesting that obesity accelerates adrenarche but not the maturation of the hypothalamic-pituitary-ovarian axis. The LH/FSH peak ratio was more frequently pubertal in girls with a familial history of early puberty, suggesting that this maturation depends on genetic factors.

Hypothalamic-pituitary lesions in pediatric patients: endocrine symptoms often precede neuro-ophthalmic presenting symptoms.

OBJECTIVE: To evaluate whether analyses of clinical and endocrine presenting symptoms could help to shorten the time to diagnosis of hypothalamic-pituitary lesions in children. STUDY DESIGN: A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed. RESULTS: The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in our series. CONCLUSIONS: Endocrine disorders occurred in two-thirds of patients prior to the onset of the neuro-ophthalmic presenting symptom but were missed. Identifying them may help to diagnose hypothalamic-pituitary lesions earlier.

Predicting the adult height of girls with central precocious puberty.

BACKGROUND: There are no absolute criteria for identifying those girls with idiopathic central precocious puberty (CPP) who will benefit from gonadotropin-releasing hormone analog (GnRHa) treatment. Our objective was to predict at initial evaluation the differences between adult height (AH) and target height (TH) and (for untreated girls) the time between puberty onset and first menstruation. MATERIAL/METHODS: The 122 girls with CPP who reached their AH included 70 who were given GnRHa because their predicted AH was <155 cm (n=24), their luteinising hormone (LH)/follicle-stimulating hormone peaks (FSH) ratio was >0.66 (n=41) and/or their estradiol was >15 pg/ml (n=40). The other 52 were untreated because their predicted AH was >155 cm. Multiple linear regressions were performed on several subsets of variables. RESULTS: Treated: the difference between AH and TH (-0.6±5.4 cm) was predicted by (using SDS) =3.68 (height at initial evaluation - TH) - 1.94 (height at initial evaluation-predicted AH) - 4.23; R2=0.73. Untreated: the difference between AH and TH (1.7±4.3 cm) was predicted by =2.76 (height at initial evaluation - TH) - 3.68 LH/FSH peaks ratio - 3.49; R2=0.77. Time between puberty onset and first menstruation (years) was predicted by =12.2 - 1.06 age CPP - 0.4 (height at initial evaluation - TH); R2=0.75. CONCLUSIONS: A greater difference between height at initial evaluation and TH (SDS) is associated with a greater AH in treated and untreated girls, as are smaller differences between height at initial evaluation and predicted AH in treated and lower LH/FSH peaks ratios in untreated girls.

Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood.

BACKGROUND: It is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT) before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are not informative and no spermogram can be done. METHODS: We classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH). RESULTS: Ten (26%) boys had normal testicular function, 16 (42%) had isolated tubular failure and 12 (32%) also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B.Seven (21%) girls had normal ovarian function, 11 (32%) had partial and 16 (47%) complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls.FSH and inhibin B were negatively correlated in boys (P < 0.0001) and girls (P = 0.0006). Neither the age at HCT nor the interval between HCT and evaluation influenced gonadal function. CONCLUSION: The concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.

Plasma inhibin B and antimüllerian hormone concentrations in boys: discriminating between congenital hypogonadotropic hypogonadism and constitutional pubertal delay.

BACKGROUND: Inhibin B and antimüllerian hormone (AMH) are secreted by the Sertoli cells, stimulated by gonadotropins. We evaluated their use for discriminating between congenital hypogonadotropic hypogonadism (HH) and constitutional pubertal delay. MATERIAL/METHODS: Group 1 (n=39) was diagnosed with constitutional pubertal delay; group 2 (n=15), isolated HH; and group 3, pituitary stalk interruption syndrome (3a with [n=5] and 3b [n=8] without HH). RESULTS: At pubertal age, mean plasma inhibin B concentrations were similar in the groups having the same gonadotropin status. Individual concentrations were normal in groups 1 and 3b, but low in 6 group 2, and 3 group 3a patients. Four group 2, and 1 group 3a, also had low AMH. Among these 9 with low inhibin B, 1 in each group evaluated before puberty had had normal inhibin B and AMH. In contrast, inhibin B increased (P<.03) and AMH decreased (P<.02) in 7 group 3b patients from before to after puberty. There were 20 patients with inhibin B below 100 pg/mL including 4 group 1, 13 group 2, and 3 group 3a. The basal plasma follicle stimulating (FSH) and luteinizing (LH) hormone concentrations were < 1 IU/L in 18%, 36% in group 1, and in 56% and 100% in group 2. CONCLUSIONS: Before puberty, plasma inhibin B and AMH concentrations may be normal despite HH. At pubertal age, both are low in some patients with HH. These hormone values may help discriminate between HH and constitutional pubertal delay together with plasma FSH and LH.

Idiopathic central precocious puberty in girls: presentation factors.

BACKGROUND: It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP). METHODS: 353 girls monitored 0.9 +/- 0.7 year after the onset of CPP. RESULTS: The age at CPP was < 3 years in 2%, 3-7 years in 38% and 7-8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.25% of cases were obese. The increase in weight during the previous year (3.7 +/- 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001). There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP. CONCLUSION: The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.

Presentation and evolution of organic central precocious puberty according to the type of CNS lesion.

OBJECTIVE: To evaluate the influence of the type and treatment of CNS lesion causing central precocious puberty (CPP) on the presentation, hypothalamic-pituitary function and final height. PATIENTS: One hundred patients with CPP caused by central nervous system (CNS) lesion. RESULTS: The CPP was the presenting symptom of the lesion in 25 (10 boys) and occurred in 75 patients (23 boys) previously treated for lesions. These were optic glioma or astrocytoma (n = 45), hydrocephalus (n = 22), hypothalamic hamartoma (n = 15), suprasellar arachnoid cyst (n = 10) and others (n = 8). The percentages of patients with increased height, bone age advance, testicular volume, LH/FSH peaks ratio after gonadotrophin-releasing hormone (GnRH) test and plasma testosterone concentration in boys and oestradiol in girls varied from one aetiology to another. The boys with hamartoma were significantly taller and had greater bone age advance, LH peak and testosterone than boys with optic glioma. The girls with hamartoma and suprasellar arachnoid cyst were significantly younger and had greater LH peak than girls in the other groups. All patients treated for optic glioma had hypothalamic-pituitary deficiencies, including GH (100%), thyrotrophin (71.4%), corticotrophin (12.5%) and pubertal (34.3%) deficiencies. Sixty percent of those with suprasellar cysts lacked GH. Final height was below -2 SD in 15/59 (25%) patients, including 5/11 not treated with GnRH analogue, 3/5 not treated with GH despite GH deficiency, and 2 with hydrocephalus as a result of meningomyelocele. CONCLUSIONS: The type of CNS lesion influences the presentation of CPP. This is probably caused by differences in the mechanisms inducing puberty and to the hypothalamic-pituitary deficiencies associated with the CPP as a result of a lesion and/or its treatment.

Lipid profile correlates with glycemic control in young patients with type 1 diabetes mellitus.

Data on dyslipidemia in type 1 diabetes is scarce. The authors aimed to evaluate the lipid profile in patients with type 1 diabetes and its correlation to glycemic control. Ninety-four subjects (53.2% males), aged 15.4+/-4.7 (3.6-21.9 years), with disease duration of 5.0+/-3.6 years (0.3-17 years) were evaluated for heart rate, blood pressure, height, and weight. Laboratory data included total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), glycemia, glycosylated hemoglobin (HbA1c), creatinine, thyroid-stimulating hormone, antithyroid antibodies, and 24-hour microalbuminuria. Correlations were performed by the Spearman rank correlation test, and the significance level was <0.05. Mean values were TC, 168.6+/-46.6 mg/d; HDL, 43.1+/-15.3 mg/dL; LDL, 110.9+/-40.6 mg/dL; TGs, 78.3+/-48.6 mg/dL; glycemia, 204.6+/-116.7 mg/dL; and HbA1c, 11.2%+/-2.9%. High TC (43.9% vs. 10.7%; p<0.002) and LDL (51.5% vs. 10.7%; p<0.01) were more prevalent in patients 19 years and younger (n=66). HbA1c correlated with TC (r=0.30; p=0.004), LDL (r=0.28; p=0.008), TG (r=0.31; p=0.003), and TG/HDL ratio (r=0.25; p=0.01). Duration of diabetes correlated with LDL (r=0.21; p=0.04) and insulin daily doses with TG (r=0.23; p=0.04) and body mass index expressed as z scores (r=-0.28; p=0.007). There was a high prevalence of hypercholesterolemia (54.6%) in these diabetic patients, and lipid fraction levels were correlated with HbA1c. Good management of diabetes seems to be of paramount importance in controlling dyslipidemia.

[Idiopathic central precocious puberty in girls in Bahia, Brazil]. / Puberdade precoce central idiopática em meninas no estado da Bahia.

INTRODUCTION: Although the therapeutic effects of GnRH analogues (GnRHa) in central precocious puberty (CPP) have been established, clinical aspects may vary according to racial groups. OBJECTIVE AND METHODS: To describe the profile of 175 girls from Bahia, Brazil, treated with GnRHa for idiopathic CPP. RESULTS: The mulatto racial group predominated in the sample. The chronological age at puberty was 6.3 +/- 0.1 years. At diagnosis, height was 2.2 +/- 0.1 SD and body mass index (BMI) was 1.5 +/- 0.1 SD (> 2 SD in 32%), this one, inversely associated with age at onset of puberty (R = -0.20, p = 0.008). At treatment, chronological and bone ages were 8.4 +/- 0.1 years and 10.3 +/- 0.1 years, respectively. At the end of treatment (n = 52) age, BMI and height were 10.6 +/- 0.1 years, 1.6 +/- 0.2 SD and 1.9 +/- 0.2 SD, respectively. CONCLUSION: Clinical presentation and evolution were similar to other studies, independently of racial characteristics. In this sample, treatment with GnRHa was not associated to significant weight gain.

Seqüelas endócrinas da radioterapia no tratamento do câncer na infância e adolescência / Endocrine sequelae after radiotherapy in childhood and adolescence

A radioterapia resulta em endocrinopatias, osteoporose, obesidade e seqüelas neurológicas em pacientes tratados por câncer. A deficiência de GH é a complicação mais freqüente no eixo hipotálamo-hipofisário. A freqüência, prazo de surgimento e gravidade da deficiência de GH dependem da dose recebida durante a irradiação craniana, mas idade à radioterapia e fracionamento da dose também são variáveis importantes. Outras anormalidades do eixo hipotálamo-hipofisário são igualmente dose-dependentes. Baixas doses de irradiação induzem puberdade precoce ou avançada, enquanto altas doses provocam deficiência gonadotrópica. Complicações endócrinas secundárias à irradiação periférica, como distúrbios gonadais ou tireoidianos são descritos. Mesmo com secreção normal de GH, o crescimento pode ser comprometido por lesões ósseas após irradiação corporal total ou crânio-espinhal. Resultados melhores sobre a estatura final têm sido obtidos com reposição de GH em associação com o tratamento da puberdade precoce ou avançada. O objetivo desta revisão é a abordagem das seqüelas endócrinas tardias da radioterapia.

Puberdade precoce central idiopática em meninas no estado da Bahia / Idiopathic central precocious puberty in girls from Bahia, Brazil

INTRODUÇÃO: Embora os efeitos benéficos do tratamento com análogos de GnRH (GnRHa) na puberdade precoce central (PPC) estejam estabelecidos, aspectos clínicos podem variar em função do grupo racial. OBJETIVO E MÉTODOS: Descrever o perfil de 175 meninas com PPC idiopática tratadas com GnRHa na Bahia, Brasil. RESULTADOS: Houve predomínio do grupo racial mulato (73,6 por cento). A puberdade iniciou-se aos 6,3 ± 0,1 anos. Ao diagnóstico, as crianças apresentavam estatura de 2,2 ± 0,1 DP e índice de massa corpórea (IMC) de 1,5 ± 0,1 DP (> 2 DP em 32 por cento), estando este, inversamente associado (R= -0,20, p= 0,008) à idade no início da puberdade. As idades cronológica e óssea foram de 8,4 ± 0,1 anos e 10,3 ± 0,1 anos, respectivamente, ao início do tratamento. No seu término (n= 52), idade, IMC e estatura (n= 52) foram 10,6 ± 0,1 anos, 1,6 ± 0,2 DP e 1,9 ± 0,2 DP, respectivamente. CONCLUSÃO: Apresentação clínica e evolução puberal foram similares a outros estudos, independente do grupo racial. O tratamento com GnRHa não resultou em ganho de peso significativo na amostra estudada.

[Endocrine sequelae after radiotherapy in childhood and adolescence]. / Seqüelas endócrinas da radioterapia no tratamento do câncer na infância e adolescência.

Radiotherapy may result in endocrine abnormalities, osteoporosis, obesity and neurological sequelae in patients treated for cancer. In the hypothalamo-pituitary area, GH deficiency is the most frequent complication. The frequency, delay of appearance and severity of GH deficiency depend most on the dose delivered during cranial irradiation but variables as age at treatment and fractionation schedule may play an important role as well. Other hypothalamo-pituitary dysfunctions are also dose-dependent. Low dose cranial irradiation may induce precocious or early puberty, while high doses are related to gonadotropin deficiency. Endocrine complications due to extracranial irradiation such as gonadal or thyroid abnormalities are described. In spite of normal GH secretion, linear growth may be impaired by bone lesions secondary to craniospinal or total body irradiation. Results on final height have been optimized by better indicators of GH therapy associated with adequate treatment of early or precocious puberty. The purpose of this review is to explore the late endocrine sequelae of radiotherapy.

Problemas endocrinológicos na adolescência / Endocrine problems in adolescence

Objetivo: descrever e discutir aspectos pertinentes ás patologias endócrinas mais freqüentes na adolescência,e a repercussão destas sob o plano corporal e psicoafetivo dos pacientes. Métodos: subsídios da literatura nacional e internacional, associados à experiência dos autores, servem de base para a elaboração de um texto que propõe diretrizes no manuseio das endocrinopatias em adolescentes. Resultados: as endocrinopatias abordadas têm impacto, tanto física quanto psiquicamente, na saúde do adolescente, embora com intensidades distintas. O diabetes mellitus, enquanto disfunção permanente, de evolução crônica, e que pode acarretar complicações limitantes, tem enfoque mais detalhado. As tireopatias e a ginecomastia são muitas vezes autolimitadas, podendo, contudo, causar sofrimento e diminuição da auto-estima no adolescente. Conclusão: a repercussão dessas patologias, principalmente do diabetes mellitus e da ginecomastia, sobre a sexualidade deve ser considerada na abordagem dessa população