Serum Irisin Levels in Central Precocious Puberty and Its Variants.

AIM: The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context. METHODS: A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels. RESULTS: Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ±â€…62.35 ng/mL; PP variants group: 529.60 ±â€…39.66 ng/mL; and control group: 325.03 ±â€…27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS. CONCLUSIONS: The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.

Prevalence and clinical characteristics of isolated forms of central precocious puberty: a cohort study at a single academic center.

OBJECTIVE: Isolated central precocious puberty (CPP) includes sporadic, familial and adoption-related forms, and the characterization of its etiology is challenging. This study investigated the prevalence and clinical characteristics of isolated CPP. DESIGN AND METHODS: This observational cohort study included all patients (n = 395) with CPP included in the database of a single academic pediatric care center over a period of 11.5 years. RESULTS: In total, 332 of the 395 patients (84%) had isolated forms of CPP; the proportion of male patients was lower in this group than for non-isolated CPP (4 vs 33%, P < 0.0001). These patients had sporadic (n = 228, 68.5%), familial (n = 82, 25%) or adoption-related (n = 22, 6.5%) forms. Clinical characteristics at diagnosis were similar between groups, but girls with sporadic CPP were older at referral than those with familial or adoption-related CPP (P < 0.02), and birth weight SDS was lower in adopted patients than in those from the sporadic and familial groups (P < 0.01). In the 72 families containing patients with familial forms, both recessive and dominant transmissions were observed between first-degree relatives. Potential maternal or paternal transmission was identified in two-thirds of the studied families, in similar proportions. An autosomal dominant mode of transmission with low penetrance was suggested by the high proportion of affected parents (33 of the 72 families, 46%). Clinical presentation was similar whatever the mode of inheritance. CONCLUSION: These findings highlight the need for careful monitoring of the various forms of CPP. Future studies should explore pathophysiological mechanisms, particularly for familial forms.

Pubertad precoz y temprana: evaluación y tratamiento / Early puberty: evaluation and treatment

El autor de este artículo repasa las características clínicas de la pubertad precoz y la pubertad temprana, las pruebas diagnósticas indicadas en la evaluación de los pacientes que la presentan y las recomendaciones actuales de tratamiento. (AU)

The author of this article reviews the clinical features of early puberty, the diagnostic tests for the patients ́ evaluation andthe current treatment recommendations. (AU)

[Clinical investigation of Chinese medicine syndromes in two hundred girls of advanced puberty].

UNLABELLED: OBJECTIVE To analyze the Chinese medicine (CM) syndrome typing features for girls with advanced puberty. METHODS: The CM symptoms of girls with advanced puberty in the Department of CM, Children's Hospital of Fudan University from March 2008 to March 2011 were recruited and statistically analyzed. The CM syndrome typing features were summed up. RESULTS: Yin deficiency induced fire hyperactivity syndrome (174 cases, accounting for 87.0%) occupied the highest ratio in the main syndrome diagnosis, followed by Gan depression transforming into fire syndrome (25 cases, accounting for 12.5%) and the endoretention of damp heat syndrome (1 case, accounting for 0.5%). The mean rank of the 3 syndrome types was sequenced from yin deficiency induced fire hyperactivity syndrome (462.87), Gan depression transforming into fire syndrome (287.22), and the endoretention of damp heat syndrome (146.91). Of them 149 (accounting for 74.5%) girls were diagnosed with both yin deficiency induced fire hyperactivity syndrome and Gan depression transforming into fire syndrome. Yin deficiency induced fire hyperactivity syndrome accompanied with Gan depression transforming into fire syndrome was the most often seen (88 cases, accounting for 44.0%), followed by Gan depression transforming into fire syndrome accompanied with yin deficiency induced fire hyperactivity syndrome (46 cases, accounting for 23.0%). CONCLUSIONS: Yin deficiency induced fire hyperactivity syndrome and Gan depression transforming into fire syndrome were the leading patterns of CM syndrome typing for girls with advanced puberty. It must not neglect their combinations in clinical syndrome typing.

Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty.

The decline in age at puberty in the general population has been paralleled by an increase in the number of girls referred for evaluation of precocious puberty (PP). In 1999, The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age limit for evaluation of PP in girls. However, the limited evidence on which these recommendations were based led many experts to question these new suggestions. The emergence of new European pubertal timing data evaluated by robust clinical as well as biochemical markers has broadened our insight on how to interpret the recent pubertal changes. The recent pubertal trends have resulted in a concomitant lowering of the lower limit of normality of the pubertal onset. However, evidence suggests that age at the gonadotropin and sex steroid surges have not changed. Thus, it looks as if an increasing proportion of contemporary early pubertal girls may experience isolated gonadotropin-independent thelarche rather than central PP, which may not be discernible on pubertal examination alone. Thus, the population-based limits of normality should not be directly translated into revision of age limits for evaluation of PP due to the risk of misdiagnosing rapid progressive PP as well as intracranial and other underlying pathology.

[Precocious puberty]. / Przedwczesne dojrzewanie plciowe.

Precocious puberty is an early sexual maturation before the age of 8 in case of girls and 9 in boys. There are two types: isosexual precocious puberty--characteristic are appropriate for the child's genetic and gonadal sex; and heterosexual precocious puberty--sexual characteristic are inappropriate for the genetic sex (feminizing syndrome in boys or virilizing syndrome in girls). Precocious puberty is an important problem in childhood gynecology pediatrics, endocrinology and psychology.

Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty.

OBJECTIVE: A decrease in age at pubertal onset has been observed internationally. The aim of this study was to describe a large cohort of Caucasian girls referred with signs of early puberty according to etiology and compare biochemical characteristics. METHODS: In this single-center study, we included 449 consecutive Caucasian girls who were referred with signs of early puberty during the years 1993-2009. We evaluated pubertal stage, height, weight, and bone age. FSH, LH, estradiol, and inhibin B were determined, and a standard GnRH test was performed. Brain magnetic resonance imaging was performed to rule out pathologies. RESULTS: During the period from 1993-2008, we found an increase in the number of girls in most diagnostic groups. Of 449 girls, 88 had central precocious puberty (CPP), and 12 of these had an organic origin. A total of 129 had early-normal variant (8-9 yr), 69 had premature thelarche, and 49 premature adrenarche. Receiver operating characteristic analyses revealed that basal LH was superior in predicting the maximal LH level during GnRH testing in comparison with FSH, estradiol, and inhibin B levels. Basal LH levels were above the age-related 2 sd in 26.2, 19.6, 65.1, and 75.0% of girls with, respectively, early-normal variant, premature thelarche, idiopathic CPP, and organic CPP, but LH levels below the detection limit were also seen among girls with a pubertal GnRH test. CONCLUSION: We observed an increasing number of girls referred because of early pubertal signs. An elevated basal LH was highly predictive of a pubertal GnRH test result, whereas a low LH did not exclude central pubertal activation.

Pubertad precoz / Precocious puberty

A lo largo de los últimos años la Ginecología ha ido tomando un interés creciente por los problemas de los primeros años de la vida de la mujer. Si bien es cierto que la mayor parte de la patología femenina de esos años pertenece al campo de las malformaciones congénitas –muchas de las cuales sólo se diagnostican con motivo de la llegada de la pubertad o cuando consultan por esterilidad– es evidente que las niñas pueden consultar básicamente por los mismos problemas que las mujeres adultas (infecciones, tumores o sangrado genital anormal). El dolor es un síntoma subjetivo de difícil evaluación. Constituye uno de los motivos más frecuentes de consulta ginecológica junto con la hemorragia y la leucorrea. Es difícil marcar la diferencia entre dolor agudo y crónico, ya que según diversos criterios un dolor agudo puede ser aquel que dura desde unas horas a semanas. Nos parece más fácil diferenciar como dolor agudo aquel que motiva una consulta de urgencia, frente al crónico que puede ser visto de forma diferida en la consulta común (12, 33). El objeto del presente trabajo es el estudio de su etiología, diagnóstico y tratamiento

In last few years the study of adolescence gynaecology is increasing, and although the most frequent pathology is congenital, we can find the same pathology in adolescent as in the adult women, infections, tumours, menstrual problems. Pelvic acute and chronic pain in adolescence, is the most frequent consult next with bleeding and vaginal discharge. We can define pelvic acute pain as the pain that cause urgent consult, and the pelvic chronic pain, as the one that cause not urgent consult. The aim of this article is the study of aetiology, diagnosis and treatment of pelvic acute and chronic pain in adolescence

[The abnormalities of pubertal development: a review of treatment for them].

Precocious puberty has been defined as the development of secondary sex characteristics before 8 years of age in girls. In the past, therapy with progestational agents, such as medroxyprogesterone acetate or cyproterone acetate had been used. The gonadotropine releasing hormone agonist has been used widely. The ethiologies of delayed sexual development are numerous. A series of 191 patients with delayed pubertal development is reported in this study. Gonadal dysgenesis is 39/119(32.8%), physiologic delay is 27/119(22.7%), Rokitansky syndrome is 17/119(14.3%), hyperprolactinemia is 11/119(9.2%). The girls with physiological delay, hyperprolactinemia or poly cystic ovary syndrome, have subsequent normal reproductive potential. In the treatment of abnormal pubertal development, the individual treatment is important.

Recent advances in the diagnosis and treatment of precocious puberty.

In the last two decades, the diagnosis and treatment of precocious puberty has undergone important changes. The use of supersensitive assays to determine gonadotropins and gonadal hormones has increased the sensitivity and decreased the number of blood samples required to assess the diagnosis. The introduction of gonadotropin-releasing hormone (GnRH) agonists produced a revolution in the diagnosis and treatment of this disorder. Recently, the use of long acting GnRH agonists improved the adherence of patients to medical treatment and decreased the need for uncomfortable repeated doses. The medications in the treatment of the GnRH independent causes of precocious puberty, and the important revelations in the pathophysiology of these disorders, have advanced our knowledge and management of the affected children.

[Sexual precocity].

Sexual precocity results from both GnRH-dependent and GnRH-independent mechanisms. The GnRH-dependent forms of precocious puberty can be treated effectively with long-acting agonist analogues of GnRH. However, for some children who have a poor growth rate during the analogue therapy, an additional growth hormone therapy should be considered to get them near to their normal final height. The analogue treatment could be continued until a bone age of 13 or more. The GnRH-independent forms of precocious puberty have unique mechanisms and unknown pathophysiology. For instance, even though it is known that testotoxicosis and McCune Albright syndrome are caused by the molecular mechanism disorders, further elucidation of their etiologic basis of sexual precocity is needed. Thus being, in treating the GnRH-independent forms they should be assessed for each particular disorder.

La pubertad y sus alteraciones / Puberty and it's alterations

Se revisa la fisiología de la maduración sexual, desde la vida intrauterina hasta la pubertad, con énfasis en los eventos que ocurren durante la pubertad tanto en la mujer como en el varón. Luego se describen las alteraciones que ocurren en el desarrollo de la pubertad: pubertad precoz y pubertad tardía , sus causas, metodología diagnóstica y posibilidades tarapéuticas. Y, en la tercera parte del artículo se comentan las variaciones normales de la pubertad: adrenarquia prematura, telarquia prematura, menarquia prematura y ginecomastia puberal.

Pseudopuberdade precoce por cisto folicular autonomo: relato de caso / Precocius pseudopuberty caused by autonomous follicular ovarian cyst: a case report

A puberdade precoce (PP) na menina e definida com o surgimento de caracteristicas sexuais secundarias antes dos 8 anos de idade. As causas podem ser dependentes de gonadotrofinas (PP verdadeira), independentes de gonadotrofinas (Pseudo PP) e as variantes da normalidade. O cisto folicular autonomo pode determinar sinais de PP pela producao local de estradiol. O caso relatado revela uma menina de 4 anos que apresentou sangramento vaginal, broto mamario e leucorreia fisiologica associados a presenca de um cisto folicular autonomo. O diagnostico fundamentou-se no exame fisico, grau do conteudo vaginal, determinacao radiologica da idade ossea, dosagens hormonais, ultra-sonografias pelvica e mamaria. O tratamento destes cistos pode ser conservador ou cirurgico. Neste caso, optou-se pelo uso de acetato de medroxiprogesterona que mostrou-se satisfatorio. Alem disso, foi feita uma revisao dos achados ultra-sonograficos relevantes para o diagnostico da PP

[Management of female precocious puberty]. / Conduite à tenir devant une précocité pubertaire féminine.

Occurrence of any pubertal sign before eight years of age defines premature sexual development but does not always mean precocious puberty (PP); one should distinguish borderline physiological situations which need only a follow-up and frankly pathological situations which need very precise investigations and suitable treatment. The first situations are premature thelarche, pubarche and menarche in which the height and bone maturation, pelvic ultrasonography (US) are normal for age, avoiding hormonal investigations. Conversely in the second situation, the bone age is more advanced than the height age and the pelvic US displays ovarian activity and uterine development. The next step is the characterization of the level of the mechanism of puberty: hypothalamohypophysal or ovarian: in the first case gonadotropin levels are elevated after GnRH infusion, in the second case, depressed. The aetiological diagnosis are in true PP: brain tumors malformations or hamartoma even if negative idiopathic. At ovarian level: ovarian tumors or McCune Albright syndrome or recurrent cysts. The first etiology leads to use GnRH analog in the second the treatment is more delicate.

Update on therapy for precocious puberty.

The onset of pubertal development before age 8 years in girls or 9 years in boys indicates precocious puberty. The numerous causes of precocious puberty can be classified as central or peripheral. CPP arises from premature activation of the hypothalamic-pituitary axis; therefore, it has hormonal and physical characteristics similar to normal puberty. PPP results from production of sex steroids independent of the hypothalamic-pituitary axis. All types of precocious puberty are characterized by rapid growth and skeletal advancement, leading to the paradox of the tall child becoming a short adult secondary to early epiphyseal fusion. The choice of therapy for precocious puberty is dependent on the underlying etiology with differing strategies employed for central and peripheral causes (Table 3). Long-acting GnRH-a provide effective, selective, and reversible therapy for CPP. GnRH-agonists are not effective in PPP; however, other agents such as testolactone, spironolactone, and ketoconazole can be used to manage the premature sexual maturation associated with these conditions.