RESUMEN
BACKGROUND: In 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known. METHODS: Retrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis. RESULTS: In the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed. CONCLUSION: The Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening.
Asunto(s)
Hiperplasia Suprarrenal Congénita/epidemiología , Tamizaje Neonatal/normas , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/patología , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Países Bajos/epidemiología , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
CONTEXT: Percutaneous epiphysiodesis (PE) around the knee to reduce predicted excessive final height. Studies until now included small numbers of patients and short follow-up periods. OBJECTIVE AND DESIGN: This Dutch multicentre, long-term, retrospective, follow-up study aimed to assess adult height (AH), complications, knee function and patient satisfaction after PE. The primary hypothesis was that PE around the knee in constitutionally tall boys and girls is an effective treatment for reducing final height with low complication rates and a high level of patient satisfaction. PARTICIPANTS: 77 treated adolescents and 60 comparisons. INTERVENTION: Percutaneous epiphysiodesis. OUTCOME: AH, complications, knee function, satisfaction. RESULTS: In the PE-treated group, final height was 7.0 cm (±6.3 cm) lower than predicted in boys and 5.9 cm (±3.7 cm) lower than predicted in girls. Short-term complications in file search were seen in 5.1% (three infections, one temporary nerve injury), one requiring reoperation. Long-term complications in file search were seen in 2.6% (axis deformity 1.3%, prominent head of fibula 1.3%). No significant difference in knee function was found between treated cases and comparisons. Satisfaction was high in both the comparison and PE groups; most patients in the PE group recommended PE as the treatment for close relatives with tall stature. CONCLUSION: PE is safe and effective in children with predicted excessive AH. There was no difference in patient satisfaction between the PE and comparison group. Careful and detailed counselling is needed before embarking on treatment.
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Estatura/fisiología , Epífisis/cirugía , Trastornos del Crecimiento/cirugía , Terapia de Reemplazo de Hormonas/efectos adversos , Procedimientos Ortopédicos/métodos , Satisfacción del Paciente/estadística & datos numéricos , Adolescente , Niño , Epífisis/crecimiento & desarrollo , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/inducido químicamente , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background: Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA. Objective: To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment. Methods: BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age. Results: Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation. Conclusion: This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.
Asunto(s)
Agrecanos/genética , Enfermedades del Desarrollo Óseo/genética , Hormona Liberadora de Gonadotropina/análogos & derivados , Trastornos del Crecimiento/genética , Estatura , Niño , Preescolar , Femenino , Hormona Liberadora de Gonadotropina/uso terapéutico , Trastornos del Crecimiento/tratamiento farmacológico , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , MutaciónRESUMEN
CONTEXT: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m(2) per day (â¼ 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa are unknown. OBJECTIVE: This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m(2) per day (â¼ 0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m(2) per day. METHODS: This was a longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m(2)/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m(2)/d) with 2 years of GnRHa. RESULTS: At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m(2) per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile. CONCLUSIONS: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m(2) per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m(2) per day.
Asunto(s)
Composición Corporal/efectos de los fármacos , Estatura/efectos de los fármacos , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Leuprolida/uso terapéutico , Adiposidad/efectos de los fármacos , Adolescente , Presión Sanguínea/efectos de los fármacos , Niño , Femenino , Trastornos del Crecimiento/metabolismo , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Recién Nacido Pequeño para la Edad Gestacional , Leuprolida/administración & dosificación , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. METHODS: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr of GH treatment. Cognitive functioning was measured biennially by short forms of the WPPSI-R or WISC-R, depending on age. Total IQ (TIQ) score was estimated based on two subtest scores. RESULTS: During the randomized controlled trial, mean sd scores of all subtests and mean TIQ score remained similar compared to baseline in GH-treated children with PWS, whereas in untreated controls mean subtest sd scores and mean TIQ score decreased and became lower compared to baseline. This decline was significant for the Similarities (P = 0.04) and Vocabulary (P = 0.03) subtests. After 4 yr of GH treatment, mean sd scores on the Similarities and Block design subtests were significantly higher than at baseline (P = 0.01 and P = 0.03, respectively), and scores on Vocabulary and TIQ remained similar compared to baseline. At baseline, children with a maternal uniparental disomy had a significantly lower score on the Block design subtest (P = 0.01) but a larger increment on this subtest during 4 yr of GH treatment than children with a deletion. Lower baseline scores correlated significantly with higher increases in Similarities (P = 0.04) and Block design (P < 0.0001) sd scores. CONCLUSIONS: Our study shows that GH treatment prevents deterioration of certain cognitive skills in children with PWS on the short term and significantly improves abstract reasoning and visuospatial skills during 4 yr of GH treatment. Furthermore, children with a greater deficit had more benefit from GH treatment.
Asunto(s)
Cognición/efectos de los fármacos , Hormona de Crecimiento Humana/farmacología , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Prader-Willi/tratamiento farmacológico , Adolescente , Niño , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Preescolar , Cognición/fisiología , Femenino , Humanos , Pruebas de Inteligencia , Estudios Longitudinales , Masculino , Síndrome de Prader-Willi/fisiopatología , Síndrome de Prader-Willi/psicología , Proyectos de Investigación , Factores de TiempoRESUMEN
AIM: A screening tool for psychosocial functioning of adolescents with diabetes is unavailable. We investigated whether one question using a Visual Analogue Scale that indicates a rating from the worst (0) to the best possible life (10) is related to standardized indices of psychosocial functioning and well-being in adolescents with diabetes mellitus type 1 (T1DM). METHOD: One hundred and fifty-one adolescents with T1DM and 122 healthy peers between 12 and 18 years of age were asked to rate their life on a scale, varying from 0 to 10. Behaviour problems and depressive symptoms were measured with the Youth Self-Report (YSR) and the Children's Depression Inventory (CDI). RESULTS: Adolescents with T1DM rated their life less positive in comparison with their healthy peers (F(1,269) = 14.01, p = 0.000). Adolescents with T1DM who rated their life with a 6 or lower reported more depressive symptoms and behaviour problems (F(2,131) = 24.19, p = 0.00) compared to those with higher scores (7 or up). CONCLUSION: One question the 'rate your life scale' identified most of the adolescents at risk of internalizing behaviour problems, especially depression. The results of this first step in exploring the validity of this question as a screening tool for psychological functioning are promising.
Asunto(s)
Trastornos de la Conducta Infantil/diagnóstico , Depresión/diagnóstico , Diabetes Mellitus Tipo 1/psicología , Tamizaje Masivo/métodos , Encuestas y Cuestionarios , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Calidad de Vida , Reproducibilidad de los Resultados , Medición de Riesgo , Autoevaluación (Psicología)RESUMEN
CONTEXT AND OBJECTIVE: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. DESIGN AND PARTICIPANTS: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo (Pl) or Ox in low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. RESULTS: Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- sd, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P < 0.001). CONCLUSIONS: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development.
Asunto(s)
Estatura/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Oxandrolona/administración & dosificación , Oxandrolona/efectos adversos , Síndrome de Turner/tratamiento farmacológico , Adolescente , Factores de Edad , Andrógenos/administración & dosificación , Andrógenos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Distribución de Chi-Cuadrado , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Países Bajos , Pubertad/efectos de los fármacos , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , Virilismo/inducido químicamenteRESUMEN
BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. SETTING: We conducted a multicenter prospective trial. DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.
Asunto(s)
Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Prader-Willi/tratamiento farmacológico , Tejido Adiposo/anatomía & histología , Peso al Nacer , Presión Sanguínea , Estatura , Peso Corporal , Densidad Ósea , Niño , Preescolar , Esquema de Medicación , Ayuno , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Estudios Prospectivos , SeguridadRESUMEN
BACKGROUND: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. OBJECTIVES: The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. DESIGN: We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GH-treated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated. RESULTS: Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. CONCLUSIONS: Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months.
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Densidad Ósea/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Prader-Willi/tratamiento farmacológico , Absorciometría de Fotón , Niño , Femenino , Hormona de Crecimiento Humana/farmacología , Humanos , Vértebras Lumbares/metabolismo , Masculino , Síndrome de Prader-Willi/metabolismo , Síndrome de Prader-Willi/fisiopatología , Pubertad , Resultado del TratamientoRESUMEN
AIMS: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone (GH) profiles and fasting insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels after 3 months of GnRHa treatment with those at baseline. METHODS: After measurement of baseline overnight profiles and IGF-I and IGFBP-3 levels, 14 short pubertal SGA boys received leuprorelide acetate depots of 3.75 mg subcutaneously, every 4 weeks. RESULTS: At baseline, mean GH levels were comparable with those of controls, whereas IGF-I and IGFBP-3 standard deviation scores (SDS) were significantly lower than zero SDS. After 3 months of GnRHa treatment, all boys showed clinical arrest of puberty. The area under the curve above zero, mean and maximum LH and FSH had significantly decreased to prepubertal levels. Peak LH during the GnRH agonist test, however, indicated insufficient pubertal suppression in 43% of boys. Overnight GH profile characteristics and IGF-I and IGFBP-3 levels did not significantly change. CONCLUSIONS: Puberty was sufficiently suppressed by GnRHa treatment, as shown by the prepubertal LH and FSH profiles. After 3 months of GnRHa treatment, overnight GH profile characteristics had not significantly changed, reflecting that GH levels are comparable for prepubertal and early pubertal boys.
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Hormona Folículo Estimulante/metabolismo , Hormona de Crecimiento Humana/metabolismo , Leuprolida/uso terapéutico , Hormona Luteinizante/metabolismo , Estatura , Niño , Trastornos del Crecimiento/tratamiento farmacológico , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Pubertad Precoz/tratamiento farmacológicoRESUMEN
OBJECTIVE: Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of autoimmune regulator (AIRE) gene mutations facilitates timely and precise diagnosis. DESIGN: AIRE mutation detection was performed in a cohort of 11 patients. Two did not meet clinical APS-1 criteria and several started with atypical presentation. METHODS: Sequencing and TaqMan genotyping were used to identify AIRE mutations. Complete AIRE deletion was confirmed and framed by real-time PCR, long-range amplification and analysis of the microsatellite markers. RESULTS: Seven different mutations were detected, three were novel: c.892G>A in exon 8, silent mutation c.462A>T in exon 3 most likely affecting splicing, and a complete deletion of a single AIRE allele ((?_68)_(1567-14_?)del). Novel (chronic otitis) and rare (systemic juvenile rheumatoid arthritis, autoimmune bronchiolitis, epilepsy) clinical presentations were observed. CONCLUSIONS: AIRE mutation detection was valuable in the diagnostics of APS-1 in patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations.
Asunto(s)
Eliminación de Gen , Pruebas Genéticas , Poliendocrinopatías Autoinmunes/genética , Factores de Transcripción/genética , Adolescente , Adulto , Niño , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Heterocigoto , Humanos , Masculino , Repeticiones de Microsatélite , Fenotipo , Mutación Puntual , Poliendocrinopatías Autoinmunes/diagnóstico , Regiones Promotoras Genéticas/genética , Proteína AIRERESUMEN
OBJECTIVE: To evaluate the effect of end-stage pediatric liver disease and liver transplantation on growth and final height. PATIENTS AND METHODS: We evaluated growth at 2 years (n = 101) and 5 years (n = 63) after pediatric liver transplantation (LTx). Twenty-three children reached final height. Height was expressed as a standard deviation score of the target height (zTH score) of each patient. RESULTS: At the first 2 years after LTx, the zTH score was significantly increased from -1.7 to -1.3 SD (P < 0.05). Growth at 2 or 5 years after LTx, expressed as DeltazTH score, was positively correlated with pretransplant growth retardation (P < 0.05). In comparison with patients with noncholestatic primary liver disease, patients with cholestatic primary liver disease were more severely growth retarded before LTx (zTH score -2.0 vs -1.2 SD, P < 0.05) and had better growth in the first 2 years after LTx (DeltazTH score +0.6 vs -0.1 SD, P < 0.05). Twelve of the 23 patients had a final height below -1.3 SD of their target height. CONCLUSIONS: Growth retardation is common in children before LTx, particularly in children with an underlying cholestatic disease. After LTx, catch-up growth was partial and was prominent only in cholestatic children who had been severely growth retarded before LTx. After LTx during childhood, approximately 50% of patients reach a final height lower than -1.3 SD of their genetic potential.
Asunto(s)
Estatura/fisiología , Trastornos del Crecimiento/epidemiología , Crecimiento/fisiología , Trasplante de Hígado , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Terapia de Inmunosupresión , Lactante , Recién Nacido , Hepatopatías/cirugía , Hepatopatías/terapia , Masculino , Factores de TiempoRESUMEN
UNLABELLED: Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce. OBJECTIVE: To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children. DESIGN: Longitudinal 6-year GH study with a randomized controlled part for 3 years. RESULTS: At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMAD(LS) SDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDS(height)) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMAD(LS) SDS. LBM SDS(height) remained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDS(height) rapidly normalized to values comparable with zero. CONCLUSION: During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDS(height )remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls.
Asunto(s)
Composición Corporal/efectos de los fármacos , Estatura/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Recién Nacido Pequeño para la Edad Gestacional , Absorciometría de Fotón , Niño , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Vértebras Lumbares , Masculino , TiempoRESUMEN
CONTEXT: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. OBJECTIVE: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses. PATIENTS: Thirty-six prepubertal short SGA children were the subjects of this study. INTERVENTION: Subjects received 1 (group A) or 2 (group B) mg GH/m(2).d. MAIN OUTCOME MEASURES: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured. RESULTS: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P < 0.009). In group B, maximum GH levels increased from 43.9-161 mU/liter (P < 0.0002), and in group A, from 57.2-104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A. CONCLUSION: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.
Asunto(s)
Estatura/fisiología , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/sangre , Recién Nacido Pequeño para la Edad Gestacional , Factor I del Crecimiento Similar a la Insulina/metabolismo , Área Bajo la Curva , Niño , Femenino , Crecimiento/efectos de los fármacos , Crecimiento/fisiología , Humanos , Recién Nacido , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , MasculinoRESUMEN
UNLABELLED: In this study, the results of percutaneous epiphysiodesis as a surgical method to decrease final height is described in 15 boys with a predicted final height of more than 205 cm. A total of 17 boys with a height prediction between 195 and 209 cm without treatment were included as controls. The study period was from 1995-2002 and patients were followed for a mean period of 3.9 years (range 2.3-6.5 years) after surgery; controls were followed for 8.3 years (range 2.0-12.1 years). Final height in the treated boys was 203.6 cm (range 195.5-214.5 cm) compared to the predicted height of 210.6 cm (range 205.7-222.7 cm). The reduction in final height versus the predicted height was 7 cm and ranged between 1.2 and 13.8 cm. Final height in the control boys was 199.9 cm (range 191.3-206.7 cm). No significant side-effects of epiphysiodesis were observed. Besides final height reduction, epiphysiodesis resulted in normalisation of body proportions, expressed as the subischial leg length/sitting height ratio. This ratio in the operated patients at final height was 0.96 (range 0.90-1.01) and in the controls 0.94 (range 0.88-1.03). CONCLUSION: Epiphysiodesis can be advised as a method to decrease final height in boys with predicted tall stature. An additional advantage of this method is a normalisation of body proportions.