RESUMO
OBJECTIVES: To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD). STUDY DESIGN: Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD. RESULTS: Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score. CONCLUSIONS: Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.
Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Fibrose Cística/fisiopatologia , Adolescente , Adulto , Doenças Ósseas Metabólicas/fisiopatologia , Remodelação Óssea , Criança , Fibrose Cística/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de RegressãoRESUMO
Growth hormone (GH) and insulin-like growth factor I (IGF-I) deficiencies have been associated with osteopenia in both children and adults. To examine the effects of growth hormone resistance on bone mineral and body composition, we studied 11 adults (mean age 30 years) with growth hormone receptor deficiency (GHRD, Laron syndrome) and 11 age- and gender-matched controls from Southern Ecuador. Bone mineral and body composition were determined by dual-energy X-ray absorptiometry. Bone physiology was assessed with biochemical markers of bone turnover and dynamic bone histomorphometry. Bone size and body composition differed markedly between subjects with GHRD and controls. Affected adults were 40 cm shorter than controls, had significantly less lean body mass, and had increased percent body fat. Bone mineral content and density (BMD) at the spine, femoral neck, and whole body were significantly lower in adults with GHRD than in controls. Mean BMD Z scores were -1.5 to -1.6 at all sites in affected women and -2.2 to -2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 +/- 0.025 versus 0.177 +/- 0.021 for affected women versus controls (p < 0.05) and 0.173 +/- 0.018 versus 0.191 +/- 0.025 for men with GHRD versus normals (p = 0.31). Urinary pyridinoline concentrations were significantly greater in adults with GHRD than in controls, while type I collagen C-telopeptide breakdown products and markers of bone formation did not differ. Differences in histomorphometry were limited to a reduction in trabecular connectivity; bone volume and formation rate were similar to controls. These data confirm the importance of the GH/IGF axis in regulating bone size and body composition. The contribution of these peptides to the acquisition and maintenance of bone mineral is less certain since volumetric bone density was preserved despite low levels of IGF-I and IGFBP-3 associated with GH resistance.
Assuntos
Composição Corporal , Densidade Óssea , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/deficiência , Fator de Crescimento Insulin-Like I/deficiência , Receptores da Somatotropina/deficiência , Absorciometria de Fóton , Adulto , Aminoácidos/urina , Estatura , Criança , Estudos de Coortes , Equador , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Vértebras Lombares/diagnóstico por imagem , Masculino , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Receptores da Somatotropina/análiseRESUMO
Treatment of adults with gonadotropin releasing hormone analogs has resulted in rapid loss in bone mineral density (BMD). We measured lumbar and femoral neck BMD by dual-energy x-ray absorptiometry during 2 years of depot leuprolide therapy in 13 girls (mean age, 7.5 years; mean bone age, 10.9 years). At baseline, BMD was elevated for age and concordant with the advanced skeletal age. During therapy with gonadotropin releasing hormone analog, BMD values increased and BMD standard deviation scores for age and skeletal age did not change.
Assuntos
Densidade Óssea/efeitos dos fármacos , Puberdade Precoce/tratamento farmacológico , Absorciometria de Fóton/instrumentação , Absorciometria de Fóton/métodos , Absorciometria de Fóton/estatística & dados numéricos , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Preparações de Ação Retardada , Feminino , Humanos , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Estudos Longitudinais , Puberdade Precoce/fisiopatologia , Fatores de TempoRESUMO
Auxological and body composition changes were studied in three adolescent patients (2 female, 1 male) with growth hormone receptor deficiency (GHRD) given insulin-like growth factor I (IGF-I), 120 micrograms/kg s.c. twice daily, plus a monthly intramuscular injection of 7.5 mg of a luteinizing hormone-releasing hormone (LHRH) analogue. Preliminary results from the first 12 months of the study show that height velocity was increased compared with the pretreatment values. This increase was probably due to the IGF-I therapy, as the LHRH analogue would have suppressed gonadotrophins and gonadal steroid production. There was a reduction in percentage body fat, and increases in lean mass and the lean:fat ratio, whole body mineral content and body calcium content, even when expressed per kg body weight. There was also a trend towards increased bone mineral density of the whole skeleton, lumbar spine and femoral structures, as well as a maturation of facial features. These preliminary results indicate that concomitant therapy with IGF-I and an LHRH analogue is safe and efficacious in inducing growth without advancing bone age in patients with GHRD.
Assuntos
Composição Corporal/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Receptores da Somatotropina/deficiência , Adolescente , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Densidade Óssea/efeitos dos fármacos , Criança , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/uso terapêutico , Transtornos do Crescimento/terapia , Humanos , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/uso terapêutico , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
We report results from 2 years of therapy with the long-acting form of the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was previously reported in short-term trials to be efficacious in the treatment of central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years, who satisfied clinical criteria including GnRH-stimulated luteinizing hormone (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L), received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol (or testosterone), insulin-like growth factor I, and GnRH-stimulated gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals with bone age determinations. Pubertal progression ceased in all patients, and menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0 cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18 months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/- 0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH value was unchanged by therapy; mean basal and peak LH values for all follow-up GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively. Basal and peak follicle-stimulating hormone (FSH) values were suppressed from 4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable levels (< 1). Comparison with untreated control patients suggested that basal LH did not completely return to prepubertal levels, whereas FSH levels were suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at 24 months. Two girls were withdrawn from the study because of reactions at injection sites, with apparent sterile abscess formation in one patient. This study provides evidence that (1) long-term treatment with depot leuprolide is characterized by immediate and sustained laboratory and clinical suppression, (2) GnRH-stimulated LH and random FSH and estradiol concentrations are useful laboratory measures of efficacy, and (3) the progressive increase in predicted adult height is temporally associated with decreased serum levels of insulin-like growth factor I and striking deceleration of bone age advancement.
Assuntos
Leuprolida/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Criança , Pré-Escolar , Preparações de Ação Retardada , Avaliação de Medicamentos , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Crescimento/efeitos dos fármacos , Humanos , Injeções Intramusculares , Fator de Crescimento Insulin-Like I/análise , Leuprolida/administração & dosagem , Leuprolida/farmacologia , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/sangue , Puberdade Precoce/fisiopatologia , Resultado do TratamentoRESUMO
Thyroid ultrasound findings in 55 patients aged 6 days to 19 years were reviewed to assess the importance of this technique in evaluating childhood thyroid disorders. Findings were correlated with the available clinical, radionuclide, and pathologic data. In 25 patients with diffuse thyroid lesions (thyroiditis, Graves disease, euthyroid goiter, iodine-induced goiter, goitrous cretinism), ultrasound revealed only homogeneous thyroid enlargement or a nonspecific patchy echo pattern. In two infants with poorly visualized glands on radionuclide scans, ultrasound confirmed the presence of anatomically normal thyroid tissue. Twenty patients had at least one focal thyroid lesion seen by ultrasound, including nodules not detected by palpation in one child or by technetium scan in three. Thyroid malignancies were found in four of 13 patients with solitary thyroid nodules, occurring in two of four patients with echogenic nodules, two of five children with complex lesions, and none of four with echofree nodules. Thyroid ultrasound is a sensitive, noninvasive means of evaluating thyroid anatomy. Because it can detect thyroid tissue in the neck not seen on radionuclide scan in patients at all ages and can define the number and consistency of focal lesions, this technique offers definite advantages in assessing a variety of childhood thyroid disorders.