Asunto(s)
Abdomen Agudo/etiología , Cuerpos Extraños/complicaciones , Cuerpos Extraños/cirugía , Fístula Intestinal/etiología , Perforación Intestinal/etiología , Intestino Delgado , Imanes/efectos adversos , Abdomen Agudo/diagnóstico por imagen , Abdomen Agudo/cirugía , Anastomosis Quirúrgica/métodos , Niño , Deglución , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Estudios de Seguimiento , Cuerpos Extraños/diagnóstico por imagen , Humanos , Fístula Intestinal/cirugía , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/cirugía , Laparotomía/métodos , Masculino , Radiografía , Resultado del TratamientoRESUMEN
Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is highly expressed in the anterior pituitary gland, and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass. Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling.
Asunto(s)
Hipotiroidismo Congénito/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Inmunoglobulinas/genética , Proteínas de la Membrana/genética , Mutación , Enfermedades Testiculares/genética , Adolescente , Adulto , Anciano , Animales , Secuencia de Bases , Niño , Preescolar , Exoma , Compuestos Ferrosos , Humanos , Lactante , Masculino , Metalocenos , Ratones , Persona de Mediana Edad , Hipófisis/metabolismo , Hipófisis/patología , Prolactina/sangre , Receptores de Hormona Liberadora de Tirotropina/biosíntesis , Análisis de Secuencia de ADN , Síndrome , Testículo/anatomía & histología , Testículo/patología , Tirotropina/sangre , Triyodotironina/análisis , Adulto JovenRESUMEN
OBJECTIVE: To validate the SICK scoring system's ability to differentiate between individuals with higher and lower probabilities of death METHOD: We performed a one year two-centre prospective evaluation of all children aged between one month and 12 years referred to the Paediatric team at St Stephens Hospital in Delhi and admitted to the Paediatric Department at West Middlesex University Hospital in London. We calculated SICK scores at presentation and correlated them with subsequent in-hospital mortality. We used discrimination by areas under receiver operating characteristic (ROC) curves to measure performance. RESULTS: We prospectively evaluated 3895 children in Delhi and 1473 children in London. The areas under the ROC curves were 84.8% in Delhi, 81.0% in London and 84.1% (95% CI 77.4-90.8%) for combined data. Hosmer-Lemeshow goodness of fit for the combined data was good (Hosmer-Lemeshow Chi-square=2.13 (p=0.345). CONCLUSIONS: We propose the SICK score as a useful triage tool at initial presentation and highlight its particular suitability for resource poor settings.
