RESUMO
OBJECTIVES: Normal short stature (NSS), defined as height below the 5th percentile for age and sex norms that is not due to illness, hormonal deficiency, or part of a dysmorphic syndrome, has been thought to have a deleterious effect on psychosocial functioning based on observations of referred populations. Recent studies of nonreferred children with NSS, however, have demonstrated normal function. This study directly compared the psychosocial functioning of referred children with NSS, nonreferred children with NSS, and children with normal stature. STUDY DESIGN: Participants, 90 children (46 boys, 44 girls) between 6 and 12 years of age (mean, 9. 6 years), were administered intelligence and achievement tests. Parents and teachers assessed adaptive and problem behaviors. Family adaptability and cohesiveness were measured. RESULTS: Intelligence and achievement for referred and nonreferred children with NSS were average. Referred children with NSS were reported to have more externalizing behavior problems and poorer social skills than nonreferred children with NSS and children in the control group. Family adaptability and cohesiveness were comparable across groups. CONCLUSIONS: Children with NSS have normal psychosocial function, and results suggest that externalizing behavior problems, attention problems, and poor social skills in children referred to clinics for NSS are inappropriately attributed to short stature.
Assuntos
Estatura , Comportamento Infantil , Desenvolvimento Infantil , Logro , Adaptação Psicológica , Atenção , Estudos de Casos e Controles , Criança , Transtornos do Comportamento Infantil/psicologia , Família , Feminino , Humanos , Inteligência , Masculino , Encaminhamento e Consulta , Ajustamento SocialRESUMO
Langerhans cell histiocytosis may be seen with goiter and histiocytic infiltration of the thyroid. We report a 2 1/2-year-old boy who had goiter and primary hypothyroidism develop, later had pulmonary disease, and died of neurologic involvement. Autopsy lesions suggested a transitional dendritic cell precursor of the epidermal Langerhans cell. Of the reported cases of Langerhans cell histiocytosis with goiter in children and adolescents, 82% were male when the relative incidence of Langerhans cell histiocytosis is two males to one female.
Assuntos
Células Dendríticas , Bócio/complicações , Histiocitose de Células de Langerhans/complicações , Hipotireoidismo/complicações , Pré-Escolar , Evolução Fatal , Bócio/patologia , Histiocitose de Células de Langerhans/patologia , Humanos , Hipotireoidismo/patologia , Masculino , Glândula Tireoide/patologiaRESUMO
GH insensitivity due to GH receptor deficiency is a rare autosomal recessive condition, characterized by deletions or mutations of the GH receptor gene. Patients are refractory to both endogenous and exogenous GH, resulting in severe growth retardation. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) can bypass the defect in the GH receptor and potentially stimulate growth. We previously identified a genetically homogeneous group of patients in southern Ecuador, thus providing a patient base for a controlled clinical trial of rhIGF-I therapy. Seventeen prepubertal patients were entered in a randomized, double blind, placebo-controlled trial. Subjects received either a 12-month course of rhIGF-I (120 micrograms/kg, sc, daily) or 6 months of placebo followed by 6 months of rhIGF-I. Subjects receiving rhIGF-I showed a significant increase in growth rate, which was sustained over the 1-yr course of therapy (from 2.9 +/- 0.6 to 8.6 +/- 0.4 cm/yr). Incidents of hypoglycemia were equal in frequency in the placebo and rhIGF-I groups. One recipient of rhIGF-I developed papilledema, which resolved spontaneously. rhIGF-I therapy did not alter serum IGF-binding protein-3 concentrations. rhIGF-I treatment is effective in stimulating skeletal growth in GH receptor deficiency. Although the therapy proved to be safe, the potent metabolic actions of rhIGF-I and the persistently low levels of serum IGF carrier protein necessitate continued careful observation for side-effects.
Assuntos
Fator de Crescimento Insulin-Like I/uso terapêutico , Receptores da Somatotropina/deficiência , Adolescente , Estatura/efeitos dos fármacos , Proteínas de Transporte/sangue , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/efeitos adversos , Masculino , Estado Nutricional , Proteínas Recombinantes , Somatomedinas/metabolismoRESUMO
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
Cardiac function was measured in 16 prepubertal Ecuadorean patients with growth hormone receptor deficiency given insulin-like growth factor I (IGF-I) during part of a clinical trial. The IGF-I was given subcutaneously twice daily at a dose of 40 micrograms/kg on days 1 and 2, 80 micrograms/kg on days 3 and 4, and 120 micrograms/kg thereafter. Heart rate was determined at baseline (pretreatment) and on days 1-7 by repeated palpation of the radial artery and at baseline and on days 2, 4 and 7 by continuous portable Holter monitoring. Heart rate measured by both methods rose progressively with increasing doses of IGF-I. The mean palpated pulse exceeded baseline on each treatment day and was significantly higher on day 5 than day 4 and significantly higher on day 3 than day 2. The mean Holter heart rate was significantly higher on day 4 than on day 2 and significantly higher on day 2 than at baseline. Non-significant glucose and electrolyte changes did not appear to be associated with the cardiac events.
Assuntos
Frequência Cardíaca/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Receptores da Somatotropina/deficiência , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Masculino , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
Profound growth failure despite elevated GH levels in GH receptor deficiency (GHRD) results from reduced insulin-like growth factor-I (IGF-I) synthesis. Recent reports of improved growth velocity in children with GHRD during IGF-I therapy indicate growth-promoting potential in humans. We evaluated the pharmacokinetics and metabolic/hormonal effects of recombinant human IGF-I (40 micrograms/kg every 12 h) given sc for 7 days to six adults with GHRD. Hypoglycemia (< 2.5 mmol/L) did not occur, and mean 2 h postprandial insulin levels were reduced. Urinary calcium increased 2-fold (P < 0.01), and serum calcium was unchanged. The mean integrated 24-h GH level was suppressed (6.5 +/- 2.1 to 1 +/- 0.2 micrograms/L), as were the number of peaks, area under the curve, and clonidine-stimulated GH release (all P < 0.05). The mean pretreatment IGF-I level (36 +/- 2 micrograms/L) was 19% of the Ecuadorian control value (190 +/- 15 micrograms/L), it achieved a peak (253 +/- 11 micrograms/L) between 2-6 h after IGF-I injection, and at 12 h it was 137 +/- 8 micrograms/L. There were no significant changes in the half-life (8.2 +/- 1.5 to 9.7 +/- 1.9 h) or metabolic clearance (0.35 +/- 0.1 to 0.24 +/- 0.05 mL/kg.min) between days 1 and 7; however, distribution volume increased (183 +/- 10 to 266 +/- 36 mL/kg; P < 0.03). Baseline IGF-II levels were 47% of the control value and decreased during IGF-I therapy (273 +/- 10 to 178 +/- 9 micrograms/L; P < 0.01), correlating inversely with IGF-I levels (r = -0.3; P < 0.001). Although IGF-binding protein-3 (IGFBP-3) levels were not significantly influenced, baseline IGFBP-2 levels (153% of the control) increased 45% (P < 0.01). We conclude that IGF-I (40 micrograms/kg every 12 h) given sc to adults with GHRD is safe; achieves normal levels of IGF-I; reduces insulin, IGF-II, and GH levels; and increases IGFBP-2 concentrations and urinary excretion of calcium.
Assuntos
Hormônio do Crescimento/deficiência , Fator de Crescimento Insulin-Like I/farmacologia , Receptores da Somatotropina/fisiologia , Adulto , Glicemia/metabolismo , Cálcio/sangue , Cálcio/urina , Proteínas de Transporte/sangue , Clonidina , Equador , Feminino , Hormônio do Crescimento/metabolismo , Meia-Vida , Humanos , Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I/farmacocinética , Fator de Crescimento Insulin-Like I/uso terapêutico , Fator de Crescimento Insulin-Like II/metabolismo , Cinética , Masculino , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , SíndromeRESUMO
We have identified 56 patients with GH receptor deficiency (Laron syndrome) from two provinces in southern Ecuador, one group of 26 (Loja province) with a 4:1 female predominance and 30 patients from neighboring El Oro province with a normal sex ratio. There were no significant differences between the Loja and El Oro populations in stature (-5.3 to -11.5 standard deviation score), other auxologic measures, or in biochemical measures. GH binding protein, the circulating extracellular domain of the GH receptor, was measured by ligand immunofunction assay and found to be comparably low in children and adults. Levels of insulin-like growth factor (IGF)-I and -II and the GH-dependent IGF binding protein-3 (measured by RIA) were significantly greater, and GH and IGF binding protein-2 levels significantly lower in adults than children. Levels of IGF-I (adults) and IGF binding protein-3 (children and adults) correlated inversely with statural deviation from normal (P < 0.01). School performance was at an exceptionally high level, 41 out of 47 who had attended school being in the top 3 in classes of 15-50 persons.
Assuntos
Hormônio do Crescimento/deficiência , Fenótipo , Receptores da Somatotropina/fisiologia , Adolescente , Adulto , Idoso , Proteínas de Transporte/sangue , Criança , Pré-Escolar , Equador , Feminino , Hormônio do Crescimento/sangue , Humanos , Lactente , Recém-Nascido , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Approximately 60 cases of GHRD (Laron syndrome) were reported before 1990 and half of these were from Israel. We have described 47 additional patients from an inbred population of South Ecuador and have emphasized certain clinical features including: markedly advanced osseous maturation for height age; normal body proportions in childhood but child-like proportions in adults; much greater deviation of stature than head size, giving an appearance of large cranium and small facies; underweight in childhood despite the appearance of obesity and true obesity in adulthood; blue scleras; and limited elbow extension. The Ecuadorean patients differed markedly and most importantly from the other large concentration, in Israel, by being of normal or superior intelligence, suggesting a unique linkage in the Ecuadorean population. The Ecuadorean population also differed in that those patients coming from Loja province had a markedly skewed sex ratio (19 females: 2 males), while those from El Oro province had a normal sex distribution (14 females: 12 males). The phenotypic similarity between the El Oro and Loja patients indicates that this abnormal sex distribution is not a direct result of the GHRD.