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OBJECTIVES To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS The average annual incidence for Scotland was 23.9/100 000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100 000/year for age 0–4 years, 24.4/100 000/year for age 5–9 years, and 31.9/100 000/year for age 10–14 years. CONCLUSIONS The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics’ register provides a base for monitoring and research.

Item does not contain fulltext 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.

A 10-year-old boy presented with a 1-day history of recurrent vomiting and intermittent lower abdominal pain. Examination revealed lower abdominal tenderness. Inflammatory markers were normal with a negative urine dipstick. The initial working diagnosis was gastroenteritis and supportive treatment was started. However, the child's pain worsened and he developed rebound tenderness and guarding. Abdominal ultrasound findings were suggestive of appendicitis. Anteroposterior and lateral abdominal radiographs revealed a radio-opaque, ‘beaded’ foreign body (figure 1). Figure 1 Anteroposterior abdominal radiograph showing a central, radio-opaque, …

Background Congenital central hypothyroidism occurs either as isolated thyroid-stimulating hormone (TSH) deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the thyrotropin-releasing hormone receptor gene ( TRHR ) or the TSHb subunit gene ( TSHB ) are the only known causes of isolated TSH deficiency. Methods Using whole exome and candidate gene sequencing, we have studied 11 unrelated families with males exhibiting isolated TSH deficiency, testicular enlargement, and variably low serum prolactin levels. Findings We have identified eight distinct mutations and two whole gene deletions disrupting the X-linked immunoglobulin superfamily member 1 gene ( IGSF1 ) in affected males. IGSF1 encodes a pituitary-enriched plasma membrane glycoprotein; disease-associated mutations block trafficking of IGSF1 from the endoplasmic reticulum to the membrane, consistent with loss-of-protein function. Adult male IGSF1 null mice exhibit central hypothyroidism with decreased pituitary TSH content and circulating T3 levels; TSH secretion in response to TRH is blunted and pituitary TRHR mRNA levels are decreased, suggesting that impaired TRH signalling may provide the basis for hypothyroidism. Interpretation Our observations delineate a novel X-linked syndrome in which loss-of-function mutations in IGSF1 cause central hypothyroidism, testicular enlargement, and variable prolactin deficiency, and identify a previously unsuspected role for IGSF1 in hypothalamic-pituitary control of thyroid and testicular function. Variable biochemical penetrance in these families highlights the importance of genetic ascertainment in this syndrome, so that asymptomatic affected individuals can benefit from early initiation of thyroxine treatment. Funding Wellcome Trust and National Institute for Health Research Biomedical Research Centre.

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.