The incidence of Type 1 (insulin-dependent) diabetes mellitus was prospectively evaluated in Catalonia, Spain in patients up to 30 years of age during the period 1987-1990. The population at risk (0-29 years) consisted of 2,690,394 inhabitants (total population of Catalonia 5,978,638). All the cases were independently identified from four sources: endocrinologists, sales of blood glucose monitors and insulin pen injectors, diabetes societies and diabetic summer camps. The degree of ascertainment was 90.1%. The overall observed incidence rate was 10.7 per 100,000 per year, being 11.5 per 100,000 per year in the 0-14 age group. The incidence in males (12.0 per 100,000 per year) was higher than in females (9.3 per 100,000 per year), with a male/female ratio of 1.36/l. The sex differences were only present in cases over 14 years of age. Age specific incidence rates per 100,000 per year were 4.4 (confidence interval 95%: 3.2-5.7) in the age group 0-4, 9.9 (8.5-11.4) in 5-9, 17.5 (15.7-19.4) in 10-14, 11.4 (9.9-13.0) in 15-19, 11.3 (9.7-13.0) in 20-24 and 8.5 (7.2-9.9) in 25-29. There was a seasonal onset pattern, with the highest incidence in winter (December-February). We conclude that the incidence of Type 1 diabetes observed in Catalonia during the period 1987-1990 is higher than that recently reported in other Mediterranean countries. This study offers the first standardized data on Type 1 diabetes incidence in Catalonia, including cases up to 30 years, and contributes to the knowledge of the epidemiology of diabetes in South Europe.

In short SGA patients, the d3/fl-GHR genotypes do not seem to influence prepubertal or pubertal insulin sensitivity indexes or their changes over 2 yr of GH therapy (66 mug/kg.d).

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Background: GH release after stimuli classifies short children as severe idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for gestational age (AGA) or small for gestational age (SGA). GH release after stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS). Aim: To compare height gain induced by GH therapy (31.8 ± 3.5 µg/kg/day, 7.7 ± 1.6 years) started at prepubertal age and stopped at near adult-height age. Methods: A retrospective longitudinal multicenter study including184 short patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was evaluated throughout GH therapy and at adult-height age. Results: Height-SDS gain at adult-height age was similar among severe IIGHD (1.8 ± 0.8 SDS), mild IIGHD (1.6 ± 0.6 SDS), DGHR (1.7 ± 0.7 SDS) and NGHR (1.6 ± 0.7 SDS), or among IIGHD (1.7 ± 0.7 SDS), ISS (1.7 ± 0.6 SDS) and SGA (1.6 ± 0.8 SD). Conclusion: GH-release stimuli are of little help for deciding on GH therapy in the clinical management of prepubertal children with IIGHD, ISS or SGA.

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Purpose Thyroid dyshormonogenesis is a heterogeneous group of hereditary diseases produced by a total/partial blockage of the biochemical processes of thyroid-hormone synthesis and secretion. PAX8 is essential for thyroid morphogenesis and thyroid hormone synthesis. We aimed to identify PAX8 variants in patients with thyroid dyshormonogenesis and to analyze them with in-vitro functional studies. Patients and Methods Patients: Nine pediatric patients from the Catalan-screening program of Congenital Hypothyroidism, with a eutopic thyroid gland. Scintigraphies showed absent, low or normal uptake. Only one patient had a hypoplastic gland. In reevaluation, perchlorate discharge test was negative or compatible with partial iodine-organization deficit. After evaluation, eight patients showed permanent mild or severe hypothyroidism. Methods: Massive-sequencing techniques were used to detect variants in congenital hypothyroidism-related genes. In-vitro functional studies were based on transactivating activity of mutant PAX8 on a TG-gene promoter and analyzed by a dual-luciferase assays. Results We identified 7 heterozygous PAX8 exonic variants and 1 homozygous PAX8 splicing variant in 9 patients with variable phenotypes of thyroid dyshormonogenesis. Five were novel and five variants showed a statistically significant impaired transcriptional activity of TG promoter: 51-78% versus the wild type. Conclusions Nine patients presented PAX8 candidate variants. All presented eutopic thyroid gland and seven had deleterious variants. Phenotype of affected patients varies considerably, even within the same family; but, all, except the homozygous patient, presented normal eutopic thyroid gland and thyroid dyshormonogenesis. PAX8 functional studies have shown that six PAX8 variants are deleterious. Our studies have proven their effectiveness in evaluating these variants.