RESUMEN
OBJECTIVE: To evaluate the effect of growth hormone treatment on final height, phosphate metabolism, bone markers, and bone mineral density in children with X-linked hypophosphatemic rickets. STUDY DESIGN: Six patients (aged 7.8 +/- 1.8 years; height z score, -3.4 +/- 0.5) received conventional treatment (1,25-dihydroxyvitamin D(3) plus phosphate salts) combined with growth hormone (0.6-0.9 IU/kg per week, subcutaneously) (group A); 6 patients (aged 7.9 +/- 2.5 years; height z score, -2.1 +/- 0.6, P <.01 with respect to group A) received only conventional treatment (group B). RESULTS: Final height z score significantly improved in group A (-2.4 +/- 0.5, P <.03 with respect to the value at entry), whereas it did not change in group B (-2.8 +/- 0.5, P = NS). At final height, degree of body disproportion was similar between the groups (group A, 1.3 +/- 0.2; group B, 1.2 +/- 0.1; P = NS). Phosphate retention, bone markers, and radial bone mineral density increased only in group A. No adverse effects were observed. CONCLUSIONS: In poorly growing patients with X-linked hypophosphatemic rickets, growth hormone therapy combined with conventional treatment improves final height, phosphate retention, and radial bone mineral density, but it does not influence degree of body disproportion.
Asunto(s)
Estatura/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Hormona del Crecimiento/uso terapéutico , Hipofosfatemia Familiar/tratamiento farmacológico , Fosfatos/metabolismo , Adolescente , Biomarcadores/análisis , Calcitriol/administración & dosificación , Niño , Femenino , Hormona del Crecimiento/administración & dosificación , Humanos , Hipofosfatemia Familiar/fisiopatología , Masculino , Fosfatos/administración & dosificación , Proteínas Recombinantes/administración & dosificaciónRESUMEN
Four young male subjects (age range, 17 4/12 to 25 5/12 years), previously treated with human growth hormone for non-growth hormone-dependent short stature, showed reduced testicular volume and hypergonadotropic hypogonadism. They also showed impaired spermatogenesis and altered testicular texture as determined by ultrasonography. No clinical or laboratory finding showed disease associated with testicular dysfunction. An unfavorable gonadal outcome could occur in boys without growth hormone deficiency treated with human growth hormone.
Asunto(s)
Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/efectos adversos , Hipogonadismo/inducido químicamente , Testículo/efectos de los fármacos , Testículo/patología , Adolescente , Adulto , Atrofia , Niño , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Hipogonadismo/sangre , Hipogonadismo/diagnóstico por imagen , Hormona Luteinizante/sangre , Masculino , Testículo/diagnóstico por imagen , Testosterona/sangre , UltrasonografíaRESUMEN
OBJECTIVE: To evaluate the effects of treatment with recombinant human growth hormone (rhGH) on growth, mineral metabolism, and bone density in children with renal hypophosphatemic rickets (RHR). DESIGN: Long-term rhGH treatment combined with conventional therapy with 1,25-dihydroxyvitamin D3 plus inorganic phosphate salts. SETTING: Endocrine unit, department of pediatrics, university hospital. SUBJECTS: Twelve patients (5 boys; age range 4.6 to 12.5 years, median 7.0 years) were subdivided into two groups of six patients on the basis of the median of height z score (-2.41) and the median bone age/statural age (BA/SA) ratio (1.23). Group A included patients with a severe degree of short stature (height z score -3.4 +/- 0.5) (mean +/- SD) and altered BA/SA ratio (1.26 +/- 0.08); group B included patients with a lesser degree of short stature (height z score -2.1 +/- 0.6, p < 0.001 vs group A) and more normal BA/SA ratio (1.04 +/- 0.15, p < 0.01 vs group A). INTERVENTION: Group A received rhGH treatment (0.6 IU/kg per week subcutaneously) combined with conventional therapy; group B received conventional therapy alone. MEASUREMENTS: Height, growth velocity, predicted adult height, serum values of calcium, phosphate, bone alkaline phosphatase isoenzyme, osteocalcin, propeptides of type I and type III procollagen, intact parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and urinary calcium/urinary creatinine ratio and tubular maximum for phosphate reabsorption normalized to the glomerular filtration rate (TmP/GFR), as well as radial bone density, were measured at baseline and for 3 years. RESULTS: Height z score, growth velocity z score, predicted adult height, serum values of phosphate, bone alkaline phosphatase isoenzyme, osteocalcin, propeptides of type I and type III procollagen, intact parathyroid hormone 1,25-dihydroxyvitamin D, and TmP/GFR, as well as radial bone density, improved significantly only in group A. Serum calcium and 25-hydroxyvitamin D, and urinary calcium/urinary creatinine ratio did not change in either group. CONCLUSIONS: Long-term rhGH administration may benefit growth, phosphate retention, and bone density in patients with RHR, without evidence of side effects.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Hormona del Crecimiento/uso terapéutico , Crecimiento/efectos de los fármacos , Hipofosfatemia Familiar/tratamiento farmacológico , Minerales/metabolismo , Huesos/metabolismo , Calcitriol/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Femenino , Hormona del Crecimiento/efectos adversos , Humanos , Hipofosfatemia Familiar/metabolismo , Modelos Lineales , Masculino , Fosfatos/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The effects of growth hormone (GH) deficiency and recombinant human GH replacement (0.6 IU/kg per week) on bone and mineral metabolism in 26 GH-deficient children were studied for 12 months. Before therapy, all children had significantly reduced serum levels of osteocalcin, carboxyl-terminal propeptide of procollagen type I, and 1,25-dihydroxyvitamin D, whereas serum ionized calcium, phosphate, intact parathyroid hormone, calcitonin, and 25-hydroxyvitamin D concentrations were in the normal range. All children had significant reduction of bone density for their chronologic, statural, and bone ages. During therapy with recombinant human GH, a decrease of serum ionized calcium levels and increases of phosphate, osteocalcin, carboxyl-terminal propeptide of procollagen type I, and intact serum levels of parathyroid hormone were found. A significant increase of serum levels of 1,25-dihydroxyvitamin D was found at 12 months. The urinary phosphate/urinary creatinine ratio decreased, whereas values for nephrogenous cyclic adenosine monophosphate and the ratio of the maximum rate of renal tubular reabsorption of phosphate to the glomerular filtration rate increased. Bone density significantly improved at 12 months, with a complete recovery in 12 children (46.2%). Significant relationships were found among growth velocity, bone density, maximum tubular reabsorption/glomerular filtration rate ratio, and serum levels of carboxyl-terminal propeptide of type I procollagen. The changes in serum levels of this propeptide during the first week of recombinant human GH treatment were positively related to growth velocity at 6 and 12 months and to bone density at 12 months of treatment, whereas the changes in osteocalcin levels were not. We conclude that recombinant human GH treatment caused significant modifications of mineral metabolism and significantly increased bone density, and that measurement of serum levels of the propeptide during the first week of recombinant human GH administration may be a useful tool in predicting improved growth velocity and bone density during long-term recombinant human GH replacement.
Asunto(s)
Huesos/metabolismo , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/metabolismo , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Minerales/metabolismo , Densidad Ósea/efectos de los fármacos , Calcitriol/sangre , Calcio/sangre , Calcio/orina , Niño , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Crecimiento/efectos de los fármacos , Trastornos del Crecimiento/sangre , Trastornos del Crecimiento/orina , Humanos , Masculino , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Fosfatos/sangre , Fosfatos/orina , Procolágeno/sangre , Proteínas Recombinantes , Factores de TiempoRESUMEN
Because insulin-dependent diabetes mellitus is associated with altered electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years) and found lower serum values for total and ionized calcium, magnesium, intact PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects. All patients were given magnesium orally (6 mg/kg daily of elemental magnesium) for up to 60 days. During treatment, serum magnesium, total and ionized calcium, intact PTH, calcitriol, and osteocalcin concentrations significantly increased, reaching control values. After a 3-day low-calcium diet, the patients had a significantly reduced delta-increment of PTH and calcitriol in comparison with values obtained during hypomagnesemia. After magnesium repletion, the delta-increments of both PTH and calcitriol, in response to the low-calcium diet, were not significantly different from control values. These data suggest that magnesium deficiency plays a pivotal role in altering mineral homeostasis in insulin-dependent diabetes mellitus.