A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype.

Aim: X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype-phenotype correlation in a cohort of XLH patients. Methods: This is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study. Results: A total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%. Conclusions: Our analysis did not identify any specific genotype as a predictor. No significant genotype-phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment.

A Multifocal Pediatric Papillary Thyroid Carcinoma (PTC) Harboring the AGK-BRAF and RET/PTC3 Fusion in a Mutually Exclusive Pattern Reveals Distinct Levels of Genomic Instability and Nuclear Organization.

The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET/PTC as a prognostic marker in pediatric PTC is still under investigation. We recently showed that AGK-BRAF fusion is prevalent in young patients (mean 10 years) and associated with specific and aggressive pathological features such as multifocality and lung metastasis. In this pilot study, we report a unique patient harboring three different foci: the first was positive for AGK-BRAF fusion, the second was positive for just RET/PTC3 fusion and the third was negative for both rearrangements. To investigate whether AGK-BRAF and RET/PTC3 are associated with genomic instability and chromatin modifications, we performed quantitative fluorescence in situ hybridization (Q-FISH) of telomere repeats followed by 3D imaging analysis and 3D super-resolution Structured Illumination Microscopy (3D-SIM) to analyze the DNA structure from the foci. We demonstrated in this preliminary study that AGK-BRAF is likely associated with higher levels of telomere-related genomic instability and chromatin remodeling in comparison with RET/PTC3 foci. Our results suggest a progressive disruption in chromatin structure in AGK-BRAF-positive cells, which might explain a more aggressive disease outcome in patients harboring this rearrangement.

Requirement of FAT and DCHS protocadherins during hypothalamic-pituitary development.

Pituitary developmental defects lead to partial or complete hormone deficiency and significant health problems. The majority of cases are sporadic and of unknown cause. We screened 28 patients with pituitary stalk interruption syndrome (PSIS) for mutations in the FAT/DCHS family of protocadherins that have high functional redundancy. We identified seven variants, four of which putatively damaging, in FAT2 and DCHS2 in six patients with pituitary developmental defects recruited through a cohort of patients with mostly ectopic posterior pituitary gland and/or pituitary stalk interruption. All patients had growth hormone deficiency and two presented with multiple hormone deficiencies and small glands. FAT2 and DCHS2 were strongly expressed in the mesenchyme surrounding the normal developing human pituitary. We analyzed Dchs2-/- mouse mutants and identified anterior pituitary hypoplasia and partially penetrant infundibular defects. Overlapping infundibular abnormalities and distinct anterior pituitary morphogenesis defects were observed in Fat4-/- and Dchs1-/- mouse mutants but all animal models displayed normal commitment to the anterior pituitary cell type. Together our data implicate FAT/DCHS protocadherins in normal hypothalamic-pituitary development and identify FAT2 and DCHS2 as candidates underlying pituitary gland developmental defects such as ectopic pituitary gland and/or pituitary stalk interruption.

The use of aromatase inhibitors in boys with short stature: what to know before prescribing?

ABSTRACT Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.

AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma.

Thyroid cancer is the fastest increasing cancer worldwide in all age groups. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both adults and children. PTC genomic landscape has been extensively studied in adults, but information regarding sporadic pediatric patients is lacking. Although BRAF V600E mutation is highly prevalent in adults, this mutation is uncommon in pediatric cases. As adult and pediatric PTC is a mitogen-activated protein kinase-driven cancer, this altered pathway might be activated by different genetic events. The aim of this study was to investigate the occurrence of AGK-BRAF fusion gene, recently described in radiation-exposed pediatric PTC, in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30 pediatric PTC younger than 18 years of age at the time of diagnosis and 15 matched lymph node metastases (LNM). Primary tumors and matched LNM were screened for the presence of the AGK-BRAF fusion transcript by RT-PCR. To confirm the identity of the amplified products, randomly selected samples positive for the presence of the fusion transcripts were sequenced. Moreover, BRAF dual-color, break-apart probes confirmed BRAF rearrangement. Overall, the AGK-BRAF fusion gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired LNM was also available, which also shows the presence of AGK-BRAF fusion gene. This study described, for the first time, the presence of AGK-BRAF in sporadic pediatric PTC. Understanding the molecular events underlying pediatric PTC may improve preoperative diagnosis, allow molecular prognostication and define a therapeutic approach toward sporadic PTC patients.

Reported shoes size during GH therapy: is foot overgrowth a myth or reality?

Objectives To describe population reference values for shoes size, and to identify possible disproportional foot growth during GH therapy.Materials and methods Construction of percentile chart based on 3,651 controls (male: 1,838; female: 1,813). The GH treated group included 13 children with idiopathic short stature (ISS) and 50 children with normal height, but with height prediction below their target height; male: 26 and female: 37 mean ± SD age 13.3 ± 1.9 and 12.9 ± 1.5 years, respectively. GH (0.05 mg/kg/day) was used for 3.2 ± 1.6 years, ranging from 1.0-10.3 years. Height expressed as SDS, target height (TH) SDS, self-reported shoes size and target shoes size (TSS) SDS were recorded.Results Reference values were established showed as a foot SDS calculator available online at www.clinicalcaselearning.com/v2. Definitive shoes size was attained in controls at mean age of 13y in girls and 14y in boys (average values 37 and 40, respectively). In the study group, shoes size was -0.15 ± 0.9 and -0.02 ± 1.3 SDS, with target feet of 0.08 ± 0.8 and -0.27 ± 0.7 SDS in males and females, respectively. There was a significant positive correlation between shoes size and familial TSS, between shoes size and height and between TSS and TH. There was no correlation between duration of GH treatment and shoes size. Our data suggest that during long-term treatment with GH, patients maintain proportional growth in shoes size and height, and the expected correlation with the familial target.Conclusions We conclude that there is no excessive increase in the size of foot as estimated by the size of shoes in individuals under long term GH therapy.

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age.

OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance.

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance. .

Impact of early postnatal androgen exposure on voice development.

BACKGROUND: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. METHODS: The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. RESULTS: Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. CONCLUSIONS: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

Estudo comparativo do uso de prednisolona versus acetato de hidrocortisona no tratamento da hiperplasia adrenal congênita por deficiência da 21-hidroxilase forma clássica / Comparative study of prednisolone versus hydrocortisone acetate for treatment of patients with the classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

O tratamento da hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase forma clássica é habitualmente realizado com acetato de hidrocortisona. A hidrocortisona oral, em nosso meio, só está disponível em farmácias de manipulação. A prednisolona possui solução oral estável, comercialmente disponível, e tem como vantagem poder ser utilizada em dose única diária. O objetivo desse estudo foi comparar a eficácia da prednisolona aos resultados obtidos com o acetato de hidrocortisona. Foram estudados 15 pacientes, idade cronológica média (DP) de 7,2 anos (3,6), em dois períodos consecutivos de um ano, inicialmente utilizando a hidrocortisona (17,5 mg/m²/dia, divididos em três doses), seguida do uso de prednisolona (3 mg/m²/dia, dose única matinal). A avaliação dos tratamentos foi realizada por meio das variações do escore Z de estatura para idade cronológica (deltaZE), do escore Z de estatura para a idade óssea (deltaZEIO) e do escore Z do Índice de massa corporal (IMC) (deltaZIMC), bem como os valores da androstenediona em cada período. Não houve diferença na deltaZE, na deltaZEIO e na deltaZIMC entre os dois períodos, assim como nos valores de androstenediona. Concluiu-se que a prednisolona em dose única diária apresenta eficácia semelhante à obtida com a hidrocortisona utilizada três vezes ao dia, podendo ser considerada uma opção terapêutica nos pacientes com HAC por deficiência da 21-hidroxilase.

Hydrocortisone acetate is usually employed in the treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In Brazil, however, oral hydrocortisone acetate is only available from manipulation pharmacies. Prednisolone has stable oral pharmaceutical formulations commercially available, with the advantage of a single daily dose. The aim of this study was to compare the efficacy of oral prednisolone and oral hydrocortisone in the treatment of CAH due to 21-hydroxylase deficiency. Fifteen patients with mean (SD) chronological age of 7.2 (3.6) years, were evaluated in two consecutive 1-year periods. In the first year, hydrocortisone (17.5mg/m²/day, divided in three doses) was used in the treatment, followed by the use of prednisolone (3 mg/m²/day, once in the morning) in the second year. The comparison between the two treatments was assessed after a one-year treatment period by: variation of height standard deviation score (SDS) (delta Height SDS), variation of height SDS according to bone age (delta BA SDS), variation of body mass SDS (delta BMI SDS) and serum levels of androstenedione. No significant difference was observed in relation to the delta Height SDS, delta BA SDS and delta BMI SDS. No significant difference was observed in the serum levels of androstenedione. We conclude that the efficacy of prednisolone administered once a day orally is comparable to the oral use of hydrocortisone three times a day. Oral prednisolone may be an option for patients with CAH due to 21-hydroxylase deficiency.

Antiproliferative and apoptotic potencies of glucocorticoids: nonconcordance with their antiinflammatory and immunossuppressive properties

As potências antiinflamatória e imunossupressora dos glicocorticóides (GC) já foram bem estabelecidas previamente. No entanto, os GC também possuem atividade reguladora da proliferação celular e da morte celular programada (apoptose). O objetivo deste estudo foi determinar a potência relativa de diferentes GC na modulação da sobrevida celular. Linfoblastos cortico-sensíveis (linhagem celular CEM-C7/14) foram mantidos em cultura prolongada e submetidos ao tratamento com GC por 48h, em doses variando entre 10-8 e 10-5 molar. O índice de sobrevida celular foi quantificado pelo teste MTT (DimetilTiazol-Tetrezolium). Para cada GC avaliado, foram realizados pelo menos quatro experimentos em quadruplicata. A resposta celular aos diferentes GC foi analisada através do teste estatístico ANOVA on Ranks, enquanto a resposta ao mesmo GC em concentrações diferentes foi analisada pelo teste ANOVA for repeated measures. O EC50 de cada GC foi calculado utilizando-se o software GraphPad Prism 3.0. Durante o uso de concentrações baixas (10-8 e 10-7 molar), observou-se sobrevida semelhante dos linfoblastos após tratamento com hidrocortisona ou metilprednisolona. Nestas mesmas concentrações baixas, a sobrevida celular foi menor quando utilizou-se dexametasona, betametasona, budesonida ou mometasona. A mometasona e a metilprednisolona foram os dois GC que determinaram maior redução da sobrevida linfoblástica. Nossos resultados sugerem que as potências antiproliferativa e pró-apoptótica dos GC sejam diferentes dos efeitos antiinflamatórios e imunossupressores previamente estabelecidos para estes GC.

[Radioactive iodine therapy for Graves' disease in childhood and adolescence]. / Utilização do 131I no tratamento da doença de Basedow-Graves na infância e adolescência.

While the diagnosis of Graves' disease in childhood and adolescence is relatively straightforward, its treatment remains controversial. The first choice therapy is the use of anti-thyroid drugs, although side effects are more frequent than in adults and remission is low. Surgery is not usually indicated as initial treatment. Instead, it is generally recommended after recidive of the disease or due to side effects of medical treatment. The use of radioiodine therapy is increasing in this age group, especially in North America, and control of the hyperthyroidism is achieved in 3 to 6 months in 90% of the cases. There is no evidence that radioiodine therapy is associated with a higher risk of thyroid cancer, and the occurrence of side effects is lower than surgery. Based on the positive results obtained with this therapy, patients with poor responsiveness to medical treatment should be considered for early radioiodine therapy.

Fast acquisition sagittal T1 magnetic resonance imaging (FAST1-MRI): a new imaging approach for the diagnosis of growth hormone deficiency.

Routine magnetic resonance imaging (MRI) is an established standard method to investigate the etiology of pituitary insufficiency. Among the anatomic abnormalities usually observed, ectopic hyperintense signal on T1 sequence is the most frequently associated with pituitary dysfunction. We developed a new protocol (FAST1-MRI) which is able to detect anatomic hypothalamic-pituitary abnormalities with 100% concordance when compared to the routine MRI protocol. FAST1-MRI takes only 3.25 minutes, and is performed without contrast, sedation or anesthesia. We studied 17 controls and 31 patients with growth hormone (GH) deficiency (18/31 with abnormal MRI). Patients with ectopic hyperintense signal were shorter in height, had lower IGF-I and IGFBP-3 levels, and reduced GH response after clonidine. In conclusion, we describe a new simplified MRI protocol that we propose should be used in the diagnosis of GH deficiency.

Utilização do 131I no tratamento da doença de Basedow-Graves na infância e adolescência / Radioactive iodine therapy for Graves' disease in childhood and adolescence

Embora o diagnóstico da Doença de Graves (DG) na infância e adolescência seja relativamente fácil, seu tratamento ainda é controverso. Pode-se utilizar fármacos anti-tireoideanos (MMZ ou PTU), porém a incidência de efeitos adversos nessa faixa etária é maior que nos adultos e a taxa de remissão é baixa, mesmo com o uso prolongado. A cirurgia é pouco indicada como tratamento inicial, sendo realizada mais freqüentemente após recidiva do tratamento medicamentoso e/ou devido aos seus efeitos adversos. A utilização da radioiodoterapia na infância e adolescência vem crescendo. Com doses adequadas, ocorre o desenvolvimento de hipotireoidismo em cerca de 90 por cento dos casos num período de 3 a 6 meses. Os dados iniciais sugerem que o tratamento em crianças acima de 5 anos não parece estar associado a maior risco de carcinoma de tireóide. A prevalência de efeitos adversos é menor que na cirurgia. Pacientes que apresentam fatores clínicos ou laboratoriais de pior prognóstico evolutivo podem ter seu tratamento medicamentoso encurtado, sendo a indicação da radioiodoterapia realizada mais precocemente.

P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping.

P450c17 deficiency is an autosomal recessive disorder and a rare cause of congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and impaired production of sex hormones. We performed a clinical, hormonal, and molecular study of 11 patients from 6 Brazilian families with the combined 17alpha-hydroxylase/17,20-lyase deficiency phenotype. All patients had elevated basal serum levels of progesterone (1.8-38 ng/ml; 0.57-12 pmol/liter) and suppressed plasma renin activity. CYP17 genotyping identified 5 missense mutations. The compound heterozygous mutation R362C/W406R was found in 1 family, whereas the homozygous mutations R96W, Y329D, and P428L were seen in the other 5 families. The R96W mutation has been described as the cause of p450c17 deficiency in Caucasian patients. The other mutations were not found in 50 normal subjects screened by allele-specific oligonucleotide hybridization (Y329D, R362C, and W406R) or digestion with HphI (P428L) and were recently found in other Brazilian patients. Therefore, we elucidated the genotype of 11 individuals with p450c17 deficiency and concluded that basal progesterone measurement is a useful marker of p450c17 deficiency and that its use should reduce the misdiagnosis of this deficiency in patients presenting with male pseudohermaphroditism, primary or secondary amenorrhea, and mineralocorticoid excess syndrome.

Avaliação do eixo hipotalâmico-hipofisário-tireoidiano em crianças com síndrome de Down / Evaluation of the hypothalamic-pituitary-thyroid axis in children with Down syndrome

Objetivo: determinar a secreção de TSH em crianças comsíndrome de Down, sem quadro clínico-laboratorial clássico de hipotireoidismo. Métodos: analisou-se 14 crianças com síndrome de Down e idade média de 3,4 (Ý1,8) anos. Excluiu-se pacientes com sintomas clássicos de hipotireoidismo ou hipertireoidismo, ou que apresentas-sem anticorpos antitireóide positivos. Os pacientes foram comparados a um grupo controle de 16 pacientes com idade média de 11,8 (Ý3,8) anos e diagnóstico de baixa estatura familial ou atraso constitucional do crescimento. Foram determinadas as concentraçies de TSH, T3, T4, T4L e prolactina no tempo basal e após estímulo com TRH. Pacientes com síndrome de Down, subdivididos quanto ao TSH basal, foram comparados em relação às concentraçies basais de T3, T4, T4L e prolactina.Resultados: os valores basais de TSH e de prolactina foram significativamente majores no grupo com síndrome de Down. Após estímulo com TRH, o pico de TSH foi major no grupo com síndrome de Down. Tanto o número de pacientes com TSH basal > 5 µ.U/ml, quanto o número dos que apresentaram hiper-resposta ao estímulocom TRH (pico de TSH > 30 µ.U/ml), foi major no grupo comsíndrome de Down.Conclusões: freqüentemente, crianças portadoras de síndrome de Down apresentam elevação do TSH basal, mesmo na presença de valores basais normais de hormônios tireoidianos e anticorpos antitireóide negativos. A maioria dessas crianças (65por cento) apresenta hiper-resposta...

Densidade mineral óssea: correlaçäo com peso corporal, estatura, idade óssea e fator de crescimento símile à insulina / Bone mineral density: correlation with body weight, height, bone age and insulin-like growth factor

Objetivo: Determinar a densidade mineral óssea e o conteúdo mineral ósseo de corpo inteiro e de coluna lombar de crianças pré-púberes e correlacionar os valores obtidos com sexo, idade óssea, peso corporal, estatura e concentraçäo sérica do fator de crescimento símile à insulina 1. Métodos: Estudaram-se 26 meninos e 12 meninas com idades entre 7 e 8 anos, alunos de escola estadual em Säo Paulo. Todos apresentaram peso e estatura entre o percentil 2,5 e 97,5 da curva para crianças brasileiras, ausência de sinais clínicos de puberdade, anamnese sem relatos de doenças crônicas e exame físico normal. Foi realizada radiografia de punho e mäo esquerda para determinaçäo da idade óssea. A dosagem de fator de crescimento símile à insulina 1 foi determinada por radioimunoensaio...