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.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy

SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

Síndrome de desarrollo sexual precoz por tumor de células granulosas: presentación de un caso / Syndrome of precocious sexual development by granulomatous cell tumor: presentation of a case

Se describe un caso de tumor de ovario de células granulosa juvenil, cuya manifestación inicial fue una pubertad precoz isosexual, en una niña de tres años, de evolución progresiva y rápida, asociada a una masa hipogástrica palpable. La valoración hormonal demostró estradiol, elevado; 17aOH-progesterona, 13,44 ng/ml; la FSH inhibida, al igual que la LH, la alfa feto proteína normal. Exámenes de imagen confirmaron masa tumoral en ovario derecho. La exéresis del tumor de ovario derecho de aproximadamente 10-12 cm, sólido, bien delimitado de superficie granulosa, en conjunto con la trompa englobada en el proceso. El examen histopatológico demostró un tumor de células de la granulosa juvenil. La paciente ha evolucionado satisfactoriamente después del tratamiento quirúrgico, no presenta signos de metástasis. Las dosificaciones hormonales se encontraron dentro del rango de la normalidad.

We describe a case of juvenile ovarian tumor of granulose cells. Its initial manifestation was an isosexual precocious puberty, in a girl aged 3 years, of a rapid and progressive evolution, associated to a palpable hypogastric mass. The hormonal assessment showed estradiol, high; 17aOH-progesterona, 13,44ng/ml, inhibited FSH, the same as LH, normal alpha fetoprotein. The imaging examination confirmed a tumoral mass in the right ovary. We extirpated the right ovary tumor of nearly 10-12 cm, solid, well delimitated with a granulose surface, together with the tube involved in the process. The histopathologic examination showed a juvenile tumor of granulose cells. After the surgical treatment the patient has evolved satisfactorily, not showing symptoms of metastasis. The hormonal dosages were found in the normal range.

Altura final em criancas com puberdade precoce central: a experiência de um serviço de referência / Final Height in Children with Central Precocious Puberty the experience of a Specialized Center The Experience of a Specialized Center

Introdução: A puberdade precoce central ocorre principalmente devido a ativação precoce do eixo hipotalâmico-hipofisário-gonadal e conseqüentemente ao aumento do hormônios gonadotróficos. A prematura ativação desse eixo não envolve apenas mudanças físicas precoces da puberdade, mas também aceleração do crescimento linear e aceleração da maturação óssea, que leva a fusão das epífises ósseas de maneira prematura e à diminuição da altura final. Objetivo: Identificar a altura final de pacientes que apresentaram Puberdade Precoce Central atendidos no Serviço de Endocrinologia Pediátrica do Hospital Infantil Joana de Gusmão. Métodos: Foram avaliados os registros de pacientes que haviam atingido a AF no período de 1997-2007. As variáveis analisadas foram: sexo, idade cronológica, idade óssea, idade ao diagnóstico, idade ao atingir a altura final, tempo de tratamento até altura final, tempo de acompanhamento até a altura final, tratamento utilizado, altura no início e término do tratamento, altura predita pelo método de Bayley – Pinneau, altura-alvo e altura final ( transformada em escore z). Resultados: Foram incluídos 56 pacientes, 96,4 % do sexo feminino e 90,75 % dos pacientes apresentavam PPC idiopática. Os pacientes masculinos foram tratados com análogo do hormônio liberador de gonadotrofinas por 2,7 anos em média, enquanto que as pacientes femininas foram tratadas durante 3,1 anos. A altura final foi alcançada aos 15,1 anos nos meninos e 14,2 anos nas meninas.Conclusões: A média de altura final foi 171,25 cm no sexo masculino e 160,77 cm no sexo feminino. O escore-z de AF foi de -0,55 desvios padrão da média nos meninos e 0,04 desvios padrão da média nas meninas. A diferença entre altura final e altura alvo foi de -5,25 cm nos meninos e 2,4 cm nas meninas.

Background: Central precocious puberty is mainly due to the precocious activation of hypothalamic-pituitary-gonadal axis leading to an increase of gonadotropic hormones. The premature activation of this axis it involves not only early physical changes of puberty, but also linear growth acceleration and acceleration of bone maturation, which leads to early epiphyseal fusion and short adult height. Objective: To identify final height in central precocious puberty patients treated at Pediatric Endocrinology Service of Hospital Infantil Joana de Gusmão. Methods: The study evaluated the registration of patients that had reached the final height between 1997-2007. Data included sex, chronological age, bone age, age at diagnosis, age at final height, duration of treatment, duration of accompaniment from the start of treatment to final height, treatment used, height at the start and at the end of treatment, predicted height by Bayley – Pinneau method, target height and final height (these are transformed in z-score). Results: Fifty six patients were involved. 96,4 % were female sex and 90,75 % had idiopathic central precocious puberty. The males were treated with Gonadotropin Releasing Hormone Analogue by 2,7 years and females were treated by 3,1 years. Final height was reached at 15,1 years in boys and 14,2 years in girls. Conclusions: Final height average was 171,25 cm in males and 160,77 cm in females. The z-score of final height was -0,55 standard deviation of average in boys and 0,04 standard deviation of average in girls. The difference between final height and target height were -5,25 cm in boys and 2,4 cm in girls.

Duplication of the hypophysis associated with precocious puberty: presentation of two cases and review of pituitary embryogenesis

Duplicacão pituitária é uma malformacão rara muitas vezes associada a anomalias neurais/craniofaciais, facilmente demonstradas por imagens em ressonância magnética. Os autores descrevem duas criancas do sexo feminino com duplicacão da glândula pituitária e espessamento do hipotálamo, dismorfismo facial e desenvolvimento puberal precoce. Discute-se a etiopatogenia da duplicacão hipofisária e sua relacão com o quadro de puberdade precoce.

Tuberous sclerosis with hypothyroidism and precocious puberty.

Tuberous sclerosis complex has been associated though infrequently, with abnormalities in the endocrine tissues. Alterations in thyroid function, in patients with tuberous sclerosis have been reported rarely. We report a patient with tuberous sclerosis complex who presented with hypothyroidism and precocious puberty.

Duplicação da hipófise e da haste hipofisária: relato de um caso e revisão da literatura / Duplication of pituitary gland and stalk: case report and review of the literature

Os autores relatam um caso de uma paciente do sexo feminino, com idade cronológica de sete anos, idade óssea de 11 anos, aparecimento de mamas Tanner III bilateralmente, cuja investigação diagnóstica confirmou quadro de puberdade precoce dependente de gonadotrofinas, e a ressonância magnética da hipófise evidenciou duplicação da haste e da glândula hipofisária associada a hamartoma hipotalâmico.

The authors report a case of a female patient with chronological age of 7 years and bone age of 11 years, presenting with bilateral breast stage Tanner III and gonadotrophin-dependent precocious puberty. Magnetic resonance imaging of the sellar region demonstrated duplication of the pituitary gland and stalk associated with a hypothalamic hamartoma.

Maduración temprana: factor de riesgo de sobrepeso y obesidad durante la puberdad? / Early maturation: a risk factor of overweight and obesity during puberty?

En el Estudio Longitudinal de Caracas: 147 varones y 111 niñas entre 8 y 16 años, clasificados como de maduración temprana (Te), promedio (X) y tardía (Td), fueron evaluados en un contexto de riesgo de sobrepeso y obesidad. Las diferencias entre los grupos de maduración en: Indice de Masa Corporal (IMC), Pliegue Tricipital (PTR) y Pliegue Subescapular (PSE), Area Muscular (AM) y Area Grasa (AG), se analizaron mediante un análisis ANOVA para muestra repetidas. Un gradiente significativo Te > X > Td, se encontró en todas las variables en las niñas entre los 8 y los 16 años y en los varones del grupo de 8 a 11 años. Las medidas que reflejan grasa (PTR, PSE y AG) en los varones, no presentaron un gradiente definido a partir de los 12 años, mientras que el AM si presentó diferencias según el "tempo" de maduración en los tres grupos y el IMC entre tempranos y tardíos. En el IMC, el gradiente Te > X > Td fue significativo hasta los 11 años. Los niños de maduración temprana de los dos sexos presentan un riesgo significativo de sobrepeso y las niñas tempranas un riesgo de obesidad durante todo el seguimiento, mientras que, en los varones, el riesgo de obesidad se encontró hasta los 11 años solamente.

Desarrollo puberal y edad ósea en niños con antecedentes de desnutrición calórico-proteica grave precoz / Puberal development and bone age in children with early severe protein-energy malnutrition

La desnutrición grave y prolongada retrasa el crecimiento y desarrollo en el niño. Esto se ve objetivado en el menor tamaño corporal y el enlentecimiento dela maduración de diferentes tejidos, incluyendo el hueso. El retraso de la edad ósea alargaría el período de crecimiento recuperacional, si la situación nutricional mejorara. Se comparó, a una edad promedio de 12 años y 5 meses, el crecimiento estatural, la maduración ósea y el desarrollo puberal en 20 niños (10 niñas) que sufrieron desnutrición calórico-proteica grave precoz que requirió tratamiento hospitalario, con las de otros 20 niños de igual condición socioeconómica, edad y sexo, sin antecedentes de desnutrición. Se registraron diferencias significativas en el tamaño corporal en favor del grupo control (p<0,001) tanto entre los hombres como en las mujeres. Las edades óseas medidas en 18 niños de grupo de estudio (9 mujeres) y 17 controles (9 mujeres) mostraron un retraso leve, que no alcanzó significación, en todos los grupos. Las etapas puberales alcanzadas fueron semejantes en casos y controles para los dos sexos, independientemente del antecedente nutricional. Estos hallazgos sugieren que la desnutrición grave precoz, tratada, produce retraso en el crecimiento estatural pero no afectaría la maduración ósea y la maduración sexual

A funçäo ovariana na síndrome de McCune-Albright: uma autonomia questionada / The ovarian function in McCune-Albright syndrome: a questionable autonomy

A síndrome de McCune-Albright faz parte do diagnóstico etiológico da puberdade precoce e está associada à formaçao de cistos ovarianos, displasia fibrosa óssea e manchas cutâneas hiperpigmentadas. Outras endocrinopatia podem estar presentes levando à hiperfunçao de tiróide, paratiróide e adrenal, além de hipersecreçao de hormônio do crescimento e prolactina. A sua exata fisiopatologia nao está esclarecida, porém tem sido admitida a ocorrência de hiperfunçao glandular múltipla e autônoma decorrente da expressao inadequada da adenilciclase nos órgaos envolvidos. Contrariando a hipótese de autonomia ovariana inicial e reversível após a puberdade, relatamos o acompanhamento longitudinal, por 20 anos, de uma paciente portadora da síndrome cujo controle da hiperfunçao ovariana na infância e involuçao dos cistos ovarianos de repetiçao, na vida adulta, sempre foram conseguidos com o bloqueio da secreçao das gonadotrofinas, seja com progestágenos, seja com superanálogos do LHRH.

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

Adenoma adrenal virilizante: Reporte de un caso / Adrenal virilizing tumor: Case report

Se reporta el caso de una niña de 3 años de edad con historia de virilización precóz, en la cual lo más llamativo fueron la aparición del vello pubiano, la cliteromegalia con fusión labioescrotal y la aceleración de la velocidad de crecimiento con edad esquelética avanzada (7 años), que avanzó 11.1cm en 1 año, correspondiente entonces a 11 años cuando sólo tenía 4 años+8 meses. El sulfato de dehidroepiandrosterona y al testosterona libre en suero con sus metabolitos urinarios (17-cetosteroides)fueron los andrógenos que se encontraron elevados por encimas de los valores del adulto. El precursor del cortisol(17-alfa-hidroxiprogesterona) estuvo dentro de lo normal. El diagnóstico inicial hiperplasia adrenal congénita indujo a la terapia supresiva con cortisona y dexametasona que conllevaron a su vez a la aparición de un Sindrome de Cushing iatrogénico. La falta de supresión de la actividad androgénica fue la nueva orientación diagnóstica de tumor adrenal, que se confirmó con estudios de ecosonografía, tomografía axial computarizadas y resonancia magnética nuclear en la suprarenal izquierda. El tumor fue extraido por cirugía y la biopsia estableció un"adenoma cortical de la glándula adrenal". La evolución post-operatoria indica que aun cuando hay señales de buen pronóstico, puede haber recurencia o el inicio de una pubertad precoz isosexual