Variantes de la pubertad precoz en las niñas / Variants of precocious puberty in girls

Introducción: El inicio de la pubertad está determinado por la interacción entre factores genéticos y reguladores. En las niñas ocurre alrededor de los ocho años. Puede afectarse cuando existe una pubertad adelantada, pubertad precoz o una variante de la pubertad. Para su diferenciación los estudios imagenológicos se han convertido en una herramienta vital. Objetivo: Describir aspectos fisiopatológicos, clínico-epidemiológicos y del diagnóstico por imágenes de la pubertad precoz y de sus variantes puberales en las niñas. Métodos: Se realizó una revisión sistemática a través de términos de búsqueda según descriptores en ciencias de la salud. Se utilizaron artículos de libre acceso en las bases de datos de PubMed, SciELO y Google Académico. De un total de 125 artículos, se utilizaron 45 de mayor interés: 34 en idioma español y nueve en inglés, que incluyeron libros y revistas. Análisis e integración de la información: Constituye un desafío distinguir la pubertad precoz de la telarquia, pubarquia, adrenarquia o menarquia aislada de aparición precoz, ya que son variantes del desarrollo puberal. Para su diagnóstico es importante descartar una causa tratable subyacente. El examen físico, análisis de laboratorio y estudios por imágenes, permiten diferenciar las formas completas de sus variantes y las posibles causas que determinan la estimulación de la producción hormonal. Conclusiones: El conocimiento del desarrollo normal de la pubertad y la aparición de sus variantes en las niñas resultan de gran utilidad. Su detección temprana ayudaría a recibir atención médica y descartar mediante métodos de imágenes sus causas secundarias(AU)

Introduction: The start of puberty is determined by the interaction between genetic and regulatory factors. Among girls this occurs around the age of eight years. However, the process may be affected by the presence of early puberty, precocious puberty or a variant of puberty. Imaging studies have become a vital tool for their differentiation. Objective: Describe the pathophysiological, clinical-epidemiological and imaging diagnostic aspects of precocious puberty and its pubertal variants in girls. Methods: A systematic review was conducted using search terms obtained from health sciences descriptors. The documents reviewed were open access papers from the databases PubMed, SciELO and Google Scholar. Of a total 125 papers retrieved, a selection was made of the 45 of greatest interest: 34 in Spanish and 9 in English, including books and journals. Data analysis and integration: Distinguishing precocious puberty from thelarche, pubarche, adrenarche or isolated premature menarche is a challenge, for these are variants of pubertal development. Ruling out an underlying treatable cause is important for diagnosis. Physical examination, laboratory analysis and imaging studies make it possible to differentiate complete forms from their variants and the possible causes determining the stimulation of hormone production. Conclusions: Knowledge about the normal development of puberty and the emergence of its variants in girls is very useful. Early detection would pave the way for medical care, including imaging studies to rule out its secondary causes(AU)

Metabolic and hormonal assessment of adolescent and young adult women with prior premature adrenarche

OBJECTIVE: Follow-up studies of girls with premature adrenarche have reported the development of polycystic ovary syndrome, insulin resistance, and dyslipidemia and a propensity to cardiovascular disease. The aim of this study was to analyze the presence of these conditions in patients previously treated at the Universidade Federal do Triângulo Mineiro. METHODS: A total of 130 medical records reported premature adrenarche. One hundred and twenty-two patients were invited to participate, of whom 54 accepted; 34 patients were selected, as they had reached their final height. Anthropometric, blood glucose, insulin, and lipid and hormonal profile (LH, FSH, estradiol, 17α-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone) data were obtained, the HOMA-IR index was calculated, and pelvic ultrasonography was performed. To characterize polycystic ovary syndrome and metabolic syndrome, the Rotterdam and International Diabetes Federation criteria, respectively, were used. Data were analyzed according to measures of dispersion, frequency and correlations of interest. RESULTS: The age of the participants ranged from 15.2 to 28.2 years/months; 23.5% of the patients were overweight, 11.8% were obese, 29.4% had a large waist circumference, and 8.8% were hypertensive. None of the patients had altered glucose levels, and insulin levels and HOMA-IR were elevated in 29.4% and 38.2% of the participants, respectively; 14.7% of the patients exhibited acanthosis nigricans. The lipid profiles of the participants were variable, and one patient (2.9%) had metabolic syndrome. Polycystic ovary syndrome was found in 41.2% of patients. CONCLUSION: The percentage of patients with polycystic ovary syndrome who also had overweight, obesity and insulin resistance corroborates the literature data about the need for follow-up aiming at interventions, especially for conditions associated with cardiometabolic risk.

Interpretation of androgen and anti-Mullerian hormone profiles in a Hispanic cohort of 5- to 8-year-old girls with premature adrenarche

PURPOSE: Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5–8 years) and age and body mass index (BMI) matched controls. METHODS: Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done. RESULTS: PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m2 vs. 17.8±2.7 kg/m2). Dehydroepiandrostenedione sulfate (63.3±51.3 μg/dL vs. 29.8±17.3 μg/dL, P < 0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values ( < 14 years: reference range, 0.49–3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups. CONCLUSIONS: Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed.

Implicancias del polimorfismo de repeticiones de glutamina del receptor de andrógenos en la presentación de eventos peripuberales / Implications of androgen receptor gene glutamine repeat polymorphism in the presentation of peripubertal events

Puberty is a period of transition during which girls and boys acquire secondary sexual characteristics and reproductive capacity. The order of appearance of the pubertal traits accounts for a correct or otherwise incorrect activation of the hypothalamic-pituitary-gonadal axis. The growth of the pubic hair before 8 years in girls and 9 years in boys (precocious pubarche, PP) without any other apparent cause has been largely attributed to the early increase of adrenal androgen levels. Also, premature adrenarche (PA) was traditionally considered an extreme within the normal range, however emerging evidence links early androgen excess with the metabolic syndrome. In this context, it has been suggested that an exacerbated clinical manifestation of androgens may be related to greater sensitivity of the androgen receptor (AR). The purpose of this review is to summarize the current knowledge of the contribution of the CAG repeats polymorphisms of AR in the peripubertal manifestations of androgens with special emphasis on precocious pubarche and body composition

Desenvolvimento sexual e maturação puberal / Sexual and puberal development

Os fenômenos do desenvolvimento sexual e puberal são eventos progressivos e coordenados. Dependem de fatores cromossômicos - gênicos, gonadais e hormonais. Tais eventos nos indivíduos do sexo masculino e feminino, sendo sincrônicos, permitirão um conveniente desenvolvimento sexual e puberal. Analisar tais fenômenos é o propósito deste estudo.(AU)

The sexual and puberal modifications are coordinate and progressive during differents life phases. Many factors are involved like genic-chromosomic, gonadal and hormonal. Those events that occurred in males and females are synchronous and to create a perfect development. Our proposal is review those situations.(AU)

"Blooming too soon": A case of precocious puberty / Philippine Journal of Obstetrics and Gynecology

Precocious puberty is the onset of pubertal development at an earlier age than is expected based upon established normal standards. The cause of precocious puberty may range from a variant of normal development (eg. premature adrenarche or isolated premature thelarche) to pathologic conditions with significant risk of morbidity and even death (eg. malignant germ-cell tumor or astrocytoma). A case of an 18 month old female presenting with vaginal bleeding following a previously noted breast enlargement was described. Initial assessment based on the patient's history and physical examination is suggestive of precocious puberty. Hormonal studies indicated normal levels of FSH and LH, with an elevation in estradiol. Radiographic analysis showed a normal bone age. Cranial MRI revealed no abnormal masses. Sonographic evaluation showed bilateral cystic masses in the ovaries. A diagnosis of peripheral precocious puberty associated with functional ovarian cysts was made, and the patient was monitored for progression of pubertal development.

Growth and sex differentiation of children born small for gestational age / 소아과

The incidence of small for gestational age (SGA) births is frequent, accounting for 2.3% to 8% of all live births. Several childhood and adult diseases are related to early postnatal growth and birth size, and 10% of children born SGA may have a short stature throughout postnatal life. Additionally, they may have abnormal growth hormone (GH)-insulin like growth factor axis, HPA axis, and gonadal function. Permanent changes are detrimental in an environment of nutritional abundance, and predispose SGA children to an array of diseases in adolescence and adulthood. Such changes may also cause premature pubarche, adrenarche, and precocious puberty. The varying results from clinical studies necessitate more prospective case control studies. Reproductive tract abnormalities and reproductive dysfunction are related to SGA births. GH treatment is required for SGA infants who do not experience catch-up growth.

Adrenarquía precoz y marcadores del síndrome metabólico / Precocious adrenarche and components of metabolic syndrome

Introducción: la adrenarquia precoz (AP) puede asociarse con dislipidemia, hiperinsulinemia y hipertensión arterial en la vida adulta. Objetivo: evaluar características clínicas y de laboratorio, con énfasis en las alteraciones asociadas a síndrome metabólico, en niñas que presentaron AP. Pacientes y método: fueron evaluadas 51 niñas brasileñas: 30 con AP y 21 niñas normales. Resultados: Circunferencia cintura (65,2±11,2 cm versus 46,2±17,6 cm), presión arterial sistólica (111,3±12,3 mmHg versus 98,8±11,4 mmHg) y presión arterial diastólica (71,8±9,2 mmHg versus 65,0±8,1 mmHg) fueron más elevadas en las niñas con AP (p<0,05). Los valores de HDL fueron más bajos en el grupo con AP: 40,9±8,3 versus 43,7±5,7 (p=0,020). Las tasas de insulina (9,0±5,0 mUI/ml versus 5,2±3,0 mUI/ml), el índice HOMA-IR (3,2±1,4 versus 2,1±1,0), DHEA-S (594,2±288,2 ng/ml versus 285,8±213,9 ng/ml) y 17 OH progesterona (54,9±38,9 ng/dl versus 34,3±9,7 ng/dl, fueron más elevados en las niñas con AP (p<0,05). Conclusiones: niñas con AP presentan datos sugiriendo la presencia de resistencia insulínica y deberían ser estudiadas para prevenir aparición de síndrome metabólico.

Introduction: precocious adrenarche (PA) can be associated with dislipidemia, hyperinsulinemia and hypertension, in adult age. Objectives: to evaluate clinical and laboratory characteristics in the metabolic syndrome in the PA patients. Patients and method: we evaluated 51 brazilian girls: 30 with PA and 21 normal girls.Results: abdominal circumference (65,2±11,2 cm versus 46,2±17,6 cm), systolic blood pressure (111,3±12,3 mmHg versus 98,8±11,4 mmHg) and diastolic blood pressure (71,8±9,2 versus 65,0±8,1 mmHg), were higher in the PA group (p<0,05). HDL levels were lower in the PA group (40,9±8,3 versus 43,7±5,7 (p=0,020). Insulin (9,0±5,0 mUI/ml versus 5,2±3,0 mUI/mL), HOMA-IR index (3,2±1,4 versus 2,1±1,0), DHEA-S (594,2±288,2 ng/mL versus 285,8±213,9 ng/mL) and 17OH progesterone levels (54,9±38,9 godly versus 34,3±9,7 ng/dL) were higher in girls with PA (p<0,05). Conclusions: girls with PA usually show the presence of insulin resistance and its study is important in order to prevent metabolic syndrome in this group.

Triagem de mutações nos receptores de Angiotensina II, AGTR1 e AGTR2 e avaliação dos polimorfismos C573T e A1166C do gene AGTR1 em pacientes com adrenarca precoce idiopática / Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche / Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche

Pubarca precoce é o aparecimento de pêlos pubianos antes dos 8 anos em meninas e 9 anos em meninos, sendo sua etiologia mais freqüente a adrenarca precoce idiopática, a longo prazo, associada à síndrome metabólica. Dentre os fatores envolvidos na gênese da adrenarca precoce podemos citar a Angiotensina II (Ang II), a qual promove proliferação celular e esteroidogênese, podendo agir através de dois receptores, o tipo 1 (AT1) e o tipo 2 (AT2). Com o intuito de estudar mutações dos genes dos receptores da AngII, foram avaliadas 50 crianças com diagnóstico de adrenarca precoce idiopática e comparadas ao grupo controle de indivíduos normais. Não foram detectadas mutações dos genes AGTR1 e AGTR2, contudo dois polimorfismos foram identificados no gene AGTR1: o polimorfismo C573T (localizado no exon 5) e o A1166C (na região 3' não codificadora). A freqüência do alelo polimórfico T573 foi de 35 por cento nos pacientes e 38 por cento nos controles. O alelo polimórfico C1166 esteve presente em 24 por cento dos pacientes e em 26 por cento dos controles. Não houve diferença significante entre os grupos, assim como não houve correlação entre a freqüência dos polimorfismos C573T e A1166C e as variáveis clínicas e laboratoriais dos pacientes, ou com sua história familial de síndrome metabólica.

Precocious pubarche is the appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The most frequent etiology is idiopathic precocious adrenarche, suggested, after long-term follow-up, to be associated with metabolic syndrome. One of the factors involved in the genesis of precocious adrenarche is Angiotensin II (Ang II), which promotes cell proliferation and steroidogenesis through type 1 (AT1) and type 2 (AT2) receptors. In order to study Ang II receptors mutations, 50 children with idiopathic precocious adrenarche were evaluated and compared to a control group of normal individuals. Mutations were not detected in the AGTR1 and AGTR2 genes; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3' untranslated region). The polymorphic allele T573 was found in 35 percent of the patients and 38 percent of controls. The polymorphic allele C1166 was present in 24 percent of the patients and 26 percent of controls. There was no statistical difference between groups. There was also no correlation between the polymorphisms and clinical and laboratory findings, as well as their family history of metabolic syndrome.

Etiology and Age Incidence of Precocious Puberty / 대한소아내분비학회지

PURPOSE: Differential diagnosis of sexual precocity is important. Sexual precocity, defined as the appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys, was studied to evaluate the sex incidence and etiology of sexual precocity. METHODS: We reviewed the etiology and age incidence of precocious puberty in 14 boys and 89 girls examined between 1994. 11. 1-2002. 7. 31 at Samsung Seoul Hospital. All underwent standard anthropometric measures. They were assigned to diagnostic categories on the basis of clinical assessment, endocrine evaluation, radiologic imaging, and pelvic ultrasonography. RESULTS: In 89 girls, 27 had idiopathic precocious puberty, 3 had precocious puberty with organic brain lesion, 12 had gonadotropin-independent precocious puberty, 44 had premature thelarche, 2 had premature menarche, 1 had premature adrenarche. The majority of idiopathic precocious puberty girls(78%) were aged between 7-7.9 years. In 14 boys, 2 had idiopathic precocious puberty, 3 had precocious puberty with organic brain lesion, 6 had gonadotropin-independent precocious puberty, 3 had gynecomastia. CONCLUSION: Sexual precocity occurs more frequently in girls than boys. Premature thelarche is the most common form of sexual precosity. In boys, majority of central precocious puberty had organic brain lesion, so brain imaging study should be performed. In girls, majority of idiopathic precocious puberty were aged between 7-7.9 years. Reexamination of the age limit for defining when puberty should be considered precocious in Korean girls is necessary.