Intraindividual variation is smaller than the interindividual variation in serum TSH, free T(4), and free T(3) concentrations. This suggests that each individual may have a genetically determined thyroid function set-point. A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 284 monozygotic (MZ), 286 dizygotic same-sex (DZ), and 120 opposite-sex (OS) twin pairs were investigated. A classical twin study was performed. After adjustment for age, sex, and other covariates, the intraclass correlations of serum TSH, free T(4), and free T(3) were calculated. To elucidate the relative importance of hereditary and environmental factors on the variation of these hormone levels, quantitative genetic modeling was used. The intraclass correlations were consistently higher for MZ twin pairs than for DZ twin pairs. Regression analysis suggested that iodine intake played a small but significant role for the concentration of serum TSH and free T(4), whereas cigarette smoking was without influence. In quantitative genetic modeling, the heritability (with 95% confidence intervals) accounted for 64% (57-70%) of the variation in serum TSH concentration and 65% (58-71%) and 64% (57-70%), for the concentrations of free T(4) and free T(3), respectively. Genetic factors play a substantial role in controlling the pituitary-thyroid axis, indicating that each individual has a genetically determined thyroid function set-point. Whether this is of importance when treating individuals in whom pituitary-thyroid function has been disrupted by, e.g. hypo- or hyperthyroidism, remains to be clarified.

Objective: In euthyroid individuals, autoantibodies to thyroid peroxidase (TPOab) and thyroglobulin (Tgab) are regarded as early markers of thyroid autoimmunity. Family and twin studies suggest that development of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is under genetic influence. We aimed to estimate the relative importance of genetic and environmental effects for the presence of thyroid autoantibodies in euthyroid subjects. Methods: A representative sample of healthy twin pairs was identified through the Danish Twin Registry; 1372 individuals, divided into 283 monozygotic (MZ), 285 dizygotic same sex (DZ), and 118 opposite sex twin pairs were investigated. Serum TPOab and serum Tgab were measured. Probandwise concordance and intraclass correlations were calculated, and quantitative genetic modelling was performed. Results: Probandwise concordance and intraclass correlations were consistently higher for MZ than for DZ twin pairs indicating genetic influence. Genetic components (with 95% confidence intervals) accounted for 73% (46-89%) of the liability of being thyroid antibody positive. Adjusting for covariates (age, TSH and others), the estimate for genetic influence on serum TPOab concentrations was 61% (49-70%) in males and 72% (64 -79%) in females. For serum Tgab concentrations, the estimates were 39% (24-51%) and 75% (66-81%) respectively. Conclusions: Early markers of thyroid autoimmunity appear to be under strong genetic influence. The analyses suggest that it is the same set of genes that operate in males and females. However, complex mechanisms such as dominance and/or epistasis may be involved. European Journal of Endocrinology 154 29-38

OBJECTIVETo evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODSTwenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes and normal kidney function were randomly allocated to 12 weeks of double-blind liraglutide (titrated to a maximum dose of 1.8 mg) or placebo treatment (1:1) injected subcutaneously once daily as add on to ongoing antidiabetic treatment. Dose-corrected plasma trough liraglutide concentration was evaluated at the final trial visit as the primary outcome measure using a linear mixed model. RESULTSTwenty patients with ESRD (1:1 for liraglutide vs. placebo) and 20 control subjects (1:1) completed the study period. Dose-corrected plasma trough liraglutide concentration at the final visit was increased by 49% (95% CI 6-109, P = 0.02) in the group with ESRD compared with the control group. Initial and temporary nausea and vomiting occurred more frequently among liraglutide-treated patients with ESRD compared with control subjects (P < 0.04). Glycemic control tended to improve during the study period in both liraglutide-treated groups as assessed by daily blood glucose measurements (P < 0.01), and dose of baseline insulin was reduced in parallel (P < 0.04). Body weight was reduced in both liraglutide-treated groups (22.4 6 0.8 kg [mean 6 SE] in the group with ESRD, P = 0.22; 22.9 6 1.0 kg in the control group, P = 0.03). CONCLUSIONSPlasma liraglutide concentrations increased during treatment in patients with type 2 diabetes and ESRD, who experienced more gastrointestinal side effects. Reduced treatment doses and prolonged titration period may be advisable.