Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)

Background: The aim of this study was to investigate seasonality in the initial presentation of type 1 diabetes mellitus (T1DM) among Dutch children. Methods: Observational, nationwide study in the Netherlands. Using the national registry for both healthcare reimbursement and pharmaceutical care, data of all Dutch children (aged 0-14 years) with a diagnosis of T1DM in the period 2009-2011 were obtained. Results: During the study period (2009-2011) an average annual number of 2.909.537 children aged 0-14 lived in the Netherlands and 676 children were diagnosed with T1DM per year, translating into an annual incidence rate (IR) of T1DM of 23.2 per hundred thousand children (ptc). The annual IR differed significantly (p = 0.03) between seasons: 6.4 ptc in winter, 4.9 ptc in spring, 5.4 ptc in summer and 6.6 ptc in autumn. This pattern was present within both boys and girls Conclusions: Among Dutch children aged 0-14 years, there is seasonality in the of T1DM with a peak incidence in autumn and winter

Long-term effects of growth hormone (GH) treatment on body composition and bone mineral density in short children born small-for-gestational-age:six-year follow-up of a randomized controlled GH trial

Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce. Objective To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children. Design Longitudinal 6-year GH study with a randomized controlled part for 3 years. Results At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMAD(LS) SDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDSheight) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMAD(LS) SDS. LBM SDSheight remained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDSheight rapidly normalized to values comparable with zero. Conclusion During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDSheight remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls

Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year H

Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation

Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transporter, the gene of which is located on the X chromosome. We tested whether mutations in MCT8 cause severe psychomotor retardation and high serum triiodothyronine (T3) concentrations in five unrelated young boys. The coding sequence of MCT8 was analysed by PCR and direct sequencing of its six exons. In two patients, gene deletions of 2·4 kb and 24 kb were recorded and in three patients missense mutations Ala150Val, Arg171 stop, and Leu397Pro were identified. We suggest that this novel syndrome of X-linked psychomotor retardation is due to a defect in T3 entry into neurons through MCT8, resulting in impaired T3 action and metabolism

Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine

Context: T-3 action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T-3 uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T-3 levels. Objective: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T-3. Design: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T-3 uptake, 2) T-3 metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry. Results: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8. Conclusion: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T-3 levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T-3 in central neurons

Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome.

Item does not contain fulltextContext and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo (Pl) or Ox in low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. Results: Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- sd, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P < 0.001). Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development.01 maart 201