RESUMEN
BACKGROUND: Few children with obesity who are referred for weight management end up enroled in treatment. Factors enabling enrolment are poorly understood. Our purpose was to explore reasons for and facilitators of enrolment in paediatric weight management from the parental perspective. METHODS: Semi-structured interviews were conducted with parents of 10- to 17-year-olds who were referred to one of four Canadian weight management clinics and enroled in treatment. Interviews were audio-recorded and transcribed verbatim. Manifest/inductive content analysis was used to analyse the data, which included the frequency with which parents referred to reasons for and facilitators of enrolment. RESULTS: In total, 65 parents were interviewed. Most had a child with a BMI ≥95th percentile (n = 59; 91%), were mothers (n = 55; 85%) and had completed some post-secondary education (n = 43; 66%). Reasons for enrolment were related to concerns about the child, recommended care and expected benefits. Most common reasons included weight concern, weight loss expectation, lifestyle improvement, health concern and need for external support. Facilitators concerned the referral initiator, treatment motivation and barrier control. Most common facilitators included the absence of major barriers, parental control over the decision to enrol, referring physicians stressing the need for specialized care and parents' ability to overcome enrolment challenges. CONCLUSIONS: Healthcare providers might optimize enrolment in paediatric weight management by being proactive in referring families, discussing the advantages of the recommended care to meet treatment expectations and providing support to overcome enrolment barriers.
Asunto(s)
Padres/psicología , Obesidad Infantil/psicología , Derivación y Consulta , Programas de Reducción de Peso , Adolescente , Adulto , Actitud Frente a la Salud , Canadá/epidemiología , Niño , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Selección de Paciente , Obesidad Infantil/prevención & controlRESUMEN
The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
Asunto(s)
Metabolismo Energético/fisiología , Ghrelina/farmacología , Ghrelina/fisiología , Crecimiento y Desarrollo/fisiología , Receptores de Ghrelina/fisiología , Acilación , Adolescente , Adulto , Animales , Peso al Nacer/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Ayuno/metabolismo , Femenino , Feto/metabolismo , Mucosa Gástrica/metabolismo , Ghrelina/metabolismo , Hormona del Crecimiento/metabolismo , Crecimiento y Desarrollo/efectos de los fármacos , Crecimiento y Desarrollo/genética , Humanos , Recién Nacido , Lactancia/efectos de los fármacos , Ratones , Mutación Missense , Páncreas/metabolismo , Síndrome de Prader-Willi/tratamiento farmacológico , Síndrome de Prader-Willi/metabolismo , Embarazo/metabolismo , Ratas , Receptores de Ghrelina/genéticaRESUMEN
Triple A syndrome (AAAS, OMIM#231550) is an autosomal recessive condition characterized by adrenal insufficiency, achalasia, alacrima, neurodegeneration and autonomic dysfunction. Mutations in the AAAS gene on chromosome 12q13 have been reported in several subjects with AAAS. Over the last 5 years, we have evaluated six subjects with the clinical diagnosis of AAAS. Three subjects had mutations in the AAAS gene-- including one novel mutation (IVS8+1 G>A)-- and a broad spectrum of clinical presentations. However, three subjects with classic AAAS did not have mutations in the AAAS gene on both alleles. This finding supports the notion of genetic heterogeneity for this disorder, although other genetic mechanisms cannot be excluded.
Asunto(s)
Insuficiencia Suprarrenal/genética , Acalasia del Esófago/genética , Heterogeneidad Genética , Enfermedades del Aparato Lagrimal/genética , Proteínas , Adolescente , Adulto , Secuencia de Bases , Niño , Preescolar , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 13 , Femenino , Genes Recesivos , Humanos , Masculino , Mutación , National Institutes of Health (U.S.) , Proteínas del Tejido Nervioso , Proteínas de Complejo Poro Nuclear , Fenotipo , Síndrome , Estados UnidosRESUMEN
Exogenous administration of ghrelin increases caloric intake and stimulates growth hormone (GH) secretion, two effects that are mediated through binding of ghrelin to the GH secretagogue receptor (GHS-R). In addition, ghrelin is thought to inhibit adipogenesis by GHS-R-independent mechanisms. In adults, ghrelin is mainly produced by the stomach. In contrast, in the fetal and early postnatal period, ghrelin gene expression is abundant in the pancreas but not in the stomach. While knockout animal studies demonstrate that ghrelin is not required for perinatal development under normal nutritional conditions, the characteristics of ghrelin metabolism during fetal development suggest that ghrelin could contribute to the programming of mechanisms involved in energy balance, such as beta-cell maturation, orexigenic pathways and adipogenesis. In humans, ghrelin concentrations progressively decrease during childhood and adolescence, as well as with advancing puberty. In adolescents, similar to adults, ghrelin concentrations are inversely related to body mass index and to circulating insulin. One notable exception is the presence of elevated ghrelin concentrations in subjects with Prader-Willi syndrome, raising the possibility that ghrelin could be part of the etiology of excess food intake in this condition. These data raise a number of fascinating questions on the potential physiologic role of this hormone during growth and development.
Asunto(s)
Trastornos del Crecimiento/fisiopatología , Crecimiento y Desarrollo/fisiología , Hormonas Peptídicas/fisiología , Síndrome de Prader-Willi/fisiopatología , Animales , Ghrelina , HumanosRESUMEN
UNLABELLED: Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a source of potentially toxic free radicals. Steroidogenesis is markedly inhibited by H(2)O(2) in vitro. OBJECTIVE: to study the effects of selenium deficiency on GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed using targeted tumorigenesis. METHODS: AN4Rppc7 cells were grown for 7 days in serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by Northern blot. RESULTS: selenium deficiency caused a 99% There was a 51%, progesterone, corticosterone and aldosterone production, respectively (p<0.05 by ANOVA). StAR mRNA was not affected by selenium. CONCLUSIONS: selenium deficiency causes a marked decrease in GPx activity. Decreased steroid hormone production occurs for selenium concentrations equal or lower than 5 nM. The absence of changes in StAR mRNA content suggests that selenium deficiency does not affect cholesterol access to the mitochondria.
Asunto(s)
Corteza Suprarrenal/fisiología , Transformación Celular Neoplásica , Glutatión Peroxidasa/metabolismo , Fosfoproteínas/metabolismo , Selenio/farmacología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Corteza Suprarrenal/citología , Corteza Suprarrenal/efectos de los fármacos , Aldosterona/biosíntesis , Animales , Línea Celular , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Corticosterona/biosíntesis , Humanos , Peróxido de Hidrógeno/metabolismo , Ratones , Ratones Transgénicos , Fosfoproteínas/genética , Progesterona/biosíntesis , Regiones Promotoras Genéticas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Selenio/deficiencia , Transcripción Genética , Glutatión Peroxidasa GPX1RESUMEN
OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/etiología , Diabetes Mellitus Tipo 1/complicaciones , Proteínas de Unión al GTP/inmunología , Inmunoglobulina A/sangre , Fibras Musculares Esqueléticas/inmunología , Transglutaminasas/inmunología , Adolescente , Biopsia , Colombia Británica/epidemiología , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/metabolismo , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Hospitales Pediátricos , Humanos , Masculino , Tamizaje Masivo/métodos , Prevalencia , Estudios Prospectivos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Pruebas Serológicas/métodosRESUMEN
OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis (JDM). We investigated the prevalence of lipodystrophy and the extent of metabolic abnormalities related to lipoatrophic diabetes mellitus in patients with JDM. METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy and associated lipoatrophic diabetes mellitus. All patients underwent clinical assessment, laboratory investigations, and metabolic studies (oral glucose tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients with JDM and metabolic abnormalities known to be associated with lipodystrophy in another 8 patients. The 20 patients with JDM were categorized as follows: Group 1 (Patients 1-4) consisted of patients with lipodystrophy and either diabetes mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2 (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies; Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy, and 50% present with hypertriglyceridemia and insulin resistance. Screening for metabolic abnormalities in JDM should be included in routine followup because of the effect of lipodystrophy on longterm prognosis.
Asunto(s)
Dermatomiositis/epidemiología , Dermatomiositis/metabolismo , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/metabolismo , Lipodistrofia/epidemiología , Lipodistrofia/metabolismo , Adolescente , Autoanticuerpos/sangre , Glucemia , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperinsulinismo/epidemiología , Hiperinsulinismo/metabolismo , Insulina/sangre , Insulina/inmunología , Resistencia a la Insulina , Masculino , Prevalencia , Triglicéridos/sangreRESUMEN
Compared with euthyroid controls, patients with congenital hypothyroidism (CH) who are receiving L-T(4) treatment show elevated serum TSH relative to serum T(4) concentrations and increased T(4)/T(3) ratio. These abnormalities could be the consequence of impaired activity of the selenoenzymes deiodinases on which patients with CH rely to convert the ingested L-T(4) into active T(3). Eighteen patients (0.5-15.4 yr), diagnosed with CH in infancy, received selenomethionine (SeM, 20-60 microg selenium/day) for 3 months. The study took place in Belgium, a country where selenium intake is borderline. Compared with the values observed in age- and sex-matched euthyroid controls, patients with CH had decreased selenium, thyroglobulin and T(3) concentrations and increased TSH, reverse T(3), and T(4) concentrations and T(4)/T(3) ratio at baseline. Selenium supplementation caused a 74% increase in plasma selenium values but did not affect the activity of the selenoenzyme glutathione peroxidase used as a marker of selenium status. SeM abolished the TSH difference observed between CH patients and euthyroid controls at baseline and caused a significant decrease in thyroglobulin values. Thyroid hormone concentrations were not affected by SeM. In conclusion, our data suggest that selenium is not a limiting factor for peripheral T(4)-to-T(3) conversion in CH patients. In contrast, we find indirect evidence that SeM improves thyroid hormones feedback at the hypothalamo-pituitary level and decreases stimulation of the residual thyroid tissue, possibly suggesting greater intracellular T(4)-to-T(3) conversion.
Asunto(s)
Hipotiroidismo Congénito , Selenio/uso terapéutico , Tiroglobulina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Adolescente , Niño , Preescolar , Suplementos Dietéticos , Glutatión Peroxidasa/sangre , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/tratamiento farmacológico , Lactante , Selenio/sangre , Selenio/deficiencia , Selenometionina/administración & dosificación , Selenometionina/uso terapéutico , Tiroxina/uso terapéutico , Triyodotironina Inversa/sangreRESUMEN
OBJECTIVE: We determined whether the existing reference values for the diagnosis of micropenis are appropriate for optimal care of neonates in a multiethnic environment like Vancouver. METHODS: The stretched penile length and width were measured in 105 full-term newborn males of Caucasian (n = 40), Chinese (n = 40) and East-Indian origin (n = 25). RESULTS: Mean length -2.5 SD was used for the definition of micropenis and was 2.6, 2.5 and 2.3 cm for Caucasian, East-Indian and Chinese babies, respectively (p < 0.05). This is close to the widely accepted recommendation that a penile length of 2.4- 2.5 cm be considered as the lowest limit for the definition of micropenis. CONCLUSION: Mean penile length and diameter are slightly but significantly smaller in newborns of Chinese origin compared to newborns of Caucasian and East-Indian origins.
Asunto(s)
Pueblo Asiatico , Pene/anomalías , Terminología como Asunto , Población Blanca , Canadá , China/etnología , Anomalías Congénitas/diagnóstico , Humanos , Indonesia/etnología , Recién Nacido , MasculinoRESUMEN
OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.
Asunto(s)
Anticuerpos , Enfermedad Celíaca/epidemiología , Inmunoglobulina A/inmunología , Fibras Musculares Esqueléticas/inmunología , Transglutaminasas/inmunología , Síndrome de Turner/complicaciones , Adolescente , Adulto , Colombia Británica/epidemiología , Enfermedad Celíaca/etiología , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/metabolismo , Niño , Preescolar , Femenino , Humanos , Prevalencia , Estudios Prospectivos , Síndrome de Turner/epidemiología , Síndrome de Turner/inmunología , Síndrome de Turner/metabolismoRESUMEN
This study evaluated the perception of stature, acceptance of therapy, and psychosocial functioning in relation to age at onset and time on treatment during 2 yr of GH therapy in 31 girls with Turner's syndrome grouped by age (group A: 3.7-5.8 yr, n = 9; group B: 7.2-11.8 yr, n = 13; group C: 12.5-16.4 yr, n = 9). The growth response after 2 yr was significant in the 3 groups when calculated in terms of growth norms for untreated Turner girls (mean increase in height SD score: +1.2, +1.5, and +1.1, respectively). The effect was less marked in terms of growth norms for normal girls, particularly in group B (+0.5 SD score). Height was perceived as a problem by most patients, except in the youngest girls at the start of treatment (group A) and in the majority of the adolescents after 2 yr of GH therapy (group C), without evidence of relation to growth response during therapy. The GH injections were fairly well accepted by all patients, except those younger than 6 yr. In all patients, expected adult height was unrealistic and became more realistic with age, whereas no consistent changes were observed in relation to growth response to GH therapy. The Child Behavior Checklist revealed elevated mean scores at the behavioral subscales of attention problems (group A and B), social problems, withdrawal, and anxiety-depression (most obviously in group B). No significant changes were seen during GH therapy. In group C, an elevated mean social problem score at the Youth Self Report and a low mean social self-esteem score at the Self-Esteem Inventory were observed before therapy and showed a significant improvement during 2 yr of GH treatment. These results, however, might be biased due to an increase in social desirability during therapy. We conclude that the perception of height, acceptance of GH therapy, and psychosocial functioning in girls with Turner's syndrome show important differences between age groups, with only slight changes observed during GH therapy.
Asunto(s)
Envejecimiento , Estatura , Hormona de Crecimiento Humana/uso terapéutico , Aceptación de la Atención de Salud , Percepción , Síndrome de Turner/psicología , Adolescente , Conducta , Niño , Preescolar , Femenino , Humanos , Inteligencia , Autoimagen , Encuestas y Cuestionarios , Síndrome de Turner/tratamiento farmacológicoRESUMEN
We studied glucagon-induced growth hormone secretion in 9 patients with apnea of infancy and in 55 siblings of children who had died of sudden infant death syndrome, who were included as a comparison group. We observed a 33% decrease in growth hormone secretion in patients with apnea of infancy. However, linear growth remained normal. This finding could be related to either repeated episodes of hypoxia or to abnormal maturation of the autonomous nervous system.
Asunto(s)
Apnea/metabolismo , Glucagón/farmacología , Hormona de Crecimiento Humana/metabolismo , Muerte Súbita del Lactante , Apnea/fisiopatología , Glucemia , Femenino , Edad Gestacional , Humanos , Hidrocortisona/sangre , Lactante , Insulina/sangre , Modelos Lineales , Masculino , Núcleo FamiliarRESUMEN
Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.
Asunto(s)
Compuestos de Anilina/farmacología , Inhibidores Enzimáticos/farmacología , Intestinos/enzimología , Intestinos/microbiología , Yoduro Peroxidasa/antagonistas & inhibidores , Tiouracilo/análogos & derivados , Tiroxina/sangre , Triyodotironina/sangre , Animales , Antibacterianos/farmacología , Peso Corporal , Masculino , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley , Tiouracilo/farmacología , Glándula Tiroides/anatomía & histologíaRESUMEN
We performed glucagon stimulation tests in 59 normally growing siblings of children who died from sudden infant death syndrome. These investigations were performed to exclude a possible metabolic disorder (found in 4 siblings) as an underlying cause of sudden infant death syndrome. The remaining 55 siblings (32 boys and 23 girls) provide control data for this age range. Testing was performed at 0800 h after a 15-h fast. The median age was 98 days (range, 13-349 days). Plasma glucose and serum cortisol, insulin, and GH were determined before and 30, 60, 90, 120, 150, and 180 min after im injection of 0.1 mg/kg glucagon. No side-effects were observed during the procedure. Asymptomatic hypoglycemia was noted in 11% of the infants at least once between 120-180 min. Basal and peak GH concentrations were greater than 10 micrograms/L in 31% and 80% of the infants, respectively. There was a significant negative correlation between age and basal GH concentration [Spearman's rank correlation coefficient (rs) = -0.37; P < 0.01]. There was a significant correlation between age and glucagon-stimulated cortisol at 120, 150, and 180 min (rs) = 0.41; P < 0.005), but not between age and changes in glucose levels. There was no significant correlation between age and basal cortisol or peak GH concentrations and no difference between boys and girls for any of the variables studied. In conclusion, the glucagon stimulation test is well tolerated in very young subjects. The peak GH response to glucagon injection is independent of age between 0.5-12 months. The age-related increase in the glucagon-stimulated cortisol response despite a similar decrease in glucose suggests the existence of a postnatal maturation in the response of the pituitary-adrenal axis to stress.
Asunto(s)
Glucemia/metabolismo , Fármacos Gastrointestinales/farmacología , Glucagón/farmacología , Hormona del Crecimiento/metabolismo , Hidrocortisona/metabolismo , Insulina/metabolismo , Envejecimiento/fisiología , Glucemia/efectos de los fármacos , Ayuno , Femenino , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Lactante , Insulina/sangre , Secreción de Insulina , Cinética , Masculino , Valores de Referencia , Análisis de Regresión , Caracteres Sexuales , Factores de TiempoRESUMEN
Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944-->T944, Ala241-->Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760-->G760, Ileu180-->Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone.
Asunto(s)
Seudohipoaldosteronismo/genética , Receptores de Mineralocorticoides/genética , Adolescente , Secuencia de Bases , Southern Blotting , Preescolar , ADN Complementario/química , Femenino , Humanos , Lactante , Masculino , Mutación Puntual , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
In the rat, selenium deficiency causes a near-complete loss of the selenoenzyme type I 5'-deiodinase (5'D-I), resulting in a marked decrease in hepatic T4 to T3 conversion. In adult rats, serum T4 concentrations are consistently increased, whereas serum T3 and rT3 concentrations are unaffected or slightly decreased and increased, respectively. In rat fetuses near term, serum T4 and rT3 concentrations are not affected by selenium deficiency. We have now studied the effect of selenium deficiency on thyroid function in the neonatal rat. Weanling female rats were fed either a selenium-supplemented or a selenium-deficient diet for 4 weeks before mating and then throughout gestation and lactation. Neonatal rats were killed at 7, 14, 21, and 28 days. Selenium deficiency was confirmed by a more than 89% decrease in liver 5'D-I activity in mothers and pups. Selenium deficiency resulted in significant increases in serum T4 concentrations in 3- and 4-week-old pups. In contrast, selenium deficiency led to a striking increase in serum rT3 concentrations. The normal postnatal serum T3 surge was not affected by selenium deficiency at any age. In 2- and 4-week-old selenium-deficient pups obtained from a second litter from the same mothers, liver 5'D-I activity was markedly decreased, but thyroid 5'D-I activity was not affected. The increased serum rT3 and, less so, T4 concentrations observed in selenium-deficient pups were associated with a significant decrease in brain 5'D-II activity in 14- and 28-day-old pups and in brown adipose tissue 5'D-II activity in 14-day-old pups. In conclusion, the present study demonstrates that the increase in serum T4 concentrations consistently observed in selenium-deficient adult rats occurs only after the second week of life. The normal physiological postnatal 12-fold increase in serum T3 concentrations observed in selenium-deficient pups despite the marked decreases in liver 5'D-I and brain and brown adipose tissue 5'D-II activities suggests that T4 to T3 conversion by peripheral tissues may not be a major source of T3 in the neonate. In contrast, the thyroid gland, whose 5'D-I activity is not affected by selenium deficiency, is probably the principal source of circulating T3 in the neonate. Finally, the early and marked increase in serum rT3 concentrations observed in selenium-deficient pups suggests that liver 5'D-I is important in rT3 deiodination.
Asunto(s)
Animales Recién Nacidos/sangre , Yoduro Peroxidasa/metabolismo , Tiroxina/metabolismo , Triyodotironina/sangre , Triyodotironina/metabolismo , Tejido Adiposo Pardo/enzimología , Animales , Encéfalo/enzimología , Femenino , Hígado/enzimología , Concentración Osmolar , Ratas , Ratas Sprague-Dawley , Glándula Tiroides/enzimología , Tirotropina/sangre , Tiroxina/sangreRESUMEN
In adult male rats, selenium deficiency results in a near complete loss in the selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral deiodination of thyroxine (T4) and increased serum T4 concentrations. Serum 3,5,3'-triiodothyronine concentrations are normal or slightly decreased, and serum 3,3',5'-triiodothyronine concentrations are normal or slightly increased in selenium-deficient rats. We now report the effects of selenium deficiency on maternal and fetal thyroid hormone economy and on placental 5-deiodinase activity in the rat. Weanling female rats were fed either a selenium-deficient or selenium-supplemented diet for 4 wk before mating and then throughout gestation. Rats were killed at 21 d of gestation. Selenium deficiency was confirmed by a 95 and 94% decrease in glutathione peroxidase and a 84 and 56% decrease in liver type I outer ring 5' deiodinase activity in the mother and the fetus, respectively. In contrast to the increase in circulating T4 observed in selenium-deficient male and nonpregnant female adult rats, serum T4 was not affected by selenium deficiency in pregnant rats, but there was a 3-fold increase in serum 3,3',5'-triiodothyronine concentrations associated with a 70% decrease in maternal brain type II outer ring 5' deiodinase activity. Maternal serum 3,5,3'-triiodothyronine concentrations were decreased by 21%. Placental 5-deiodinase activity was unaffected by selenium deficiency. In the fetus, serum T4, 3,3',5'-triiodothyronine, and TSH concentrations were not affected by selenium deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)