Macroadenomas and hormone secreting adenomas are not uncommon in patients with pituitary incidentalomas. Macroadenomas should be closely monitored for tumour enlargement. All patients should undergo biochemical assessment and ophthalmological examination, since endocrine dysfunction or visual field defects may be present at the time a pituitary incidentaloma is detected.

We evaluated the technical robustness of the new commercial TBII assay using human recombinant TSH-R, and describe its use for the clinician in the routine laboratory. The human recombinant TSH-R assay (DYNOtest TRAK human) was compared to a conventional TBII assay (TSH-REZAK). Specificity was adjusted at 99.1% for both assays by ROC plot analysis including 113 healthy individuals. Sensitivity in 115 patients with active Graves' Disease (GD) was 98.2% for the DYNOtest TRAK human compared to 68.4% for the TSH-REZAK (p<0.0001). Comparison of the ROC-calculated cut off confirmed the recommended cut-off for the DYNOtest TRAK human, since 11% inhibition of tracer equals 1 IU/L, which is recommended as the grey zone. At the recommended cut-off (2 IU/L, 22% inhibition), the sensitivity is still 93.9% with 100% specificity. The ROC plot-derived cut-off of the TSH-REZAK (4.4%, 2 to 10 U/L) is below the grey zone of 10-15 U/L. At the recommended cut off of 15 U/L, the sensitivity is 43.0% with a specificity of 100%. Both assays showed a good correlation (r = 0.82, p < 0.0001); however, assay comparison revealed a constant bias in favour of the DYNOtest TRAK human. Applying the ROC plot-derived cut-off of 11 % inhibition (1 IU/L) for the DYNOtest TRAK human, we found 15 of 50 patients with autoimmune thyroiditis (AIT) and 6 of 23 patients with goitre (all < 1.5 IU/L). These patients would have been missed using the recommended 2 IU/L. The difference in sensitivity between the DYNOtest TRAK human and the TSH-REZAK was highly significant in the GD group, but not in other groups, indicating that the DYNOtest TRAK human has a higher sensitivity for GD without compromising specificity. In summary, the proposed high sensitivity of the new TBII assay using human recombinant TSH-R could be confirmed with the commercial product. This method offers a clear advantage over conventional TBII assays to confirm or exclude the diagnosis of GD. The recommended cut-off is very stringent, and until we have more information on the clinical relevance of low-level TBII between 1 and 1.5 IU/L, those patients should be monitored for the development of autoimmune thyroid disease.

Aims/hypothesis In humans, the intranasal route allows insulin to reach the brain while maintaining peripheral euglycaemia. Our aims were to examine acute (unconditioned) effects of central insulin on normal-range blood glucose and hormones in men, and to find out whether the effects of intranasal insulin can be learnt via classical conditioning. Methods In a randomised controlled trial, 32 healthy normalweight men (mean age 24.2 [SEM 0.5], mean BMI 22.4 [0.3]) received a conditioned stimulus (CS) and six administrations of either soluble H-insulin 100 (20 U [0.2 ml]; group 1; n=16) or vehicle (0.2 ml; group 2; n=16) on day 1. The CS was the tarry smell of meta-cresol (used as a stabilising vehicle in many insulin preparations and placebos). On day 2, all participants received the CS and six administrations of placebo. Participants and experimenters were blinded to group assignment. Sixteen individuals were randomised to and analysed in each group. Participants were sequentially numbered for group allocation. The main outcome measures were blood glucose and insulin, expressed as cumulative difference-from-baseline changes.

Celiac disease is associated with endomysial antibodies (EmA), which have recently been reported to be directed to tissue transglutaminase (tTG). To demonstrate binding of antibodies to recombinant tTG, human tTG was cloned, expressed by in vitro transcription/translation and used to develop novel radioligand assays for combined and single detection of immunoglobulin A (IgA) and G (IgG)-specific antibodies. IgA and IgG-tTGA were found in 43 (95.6%) of 45 patients with newly-diagnosed celiac disease verified by biopsy. In addition, all 30 sera from patients with gastrointestinal symptoms and positive EmA were positive for IgA-tTGA, and all but one serum (96.7%) had antibodies of the IgG class. Receiver-operating characteristic analysis including 574 sera from healthy controls revealed a specificity of 99.5%. By means of these new assays, we identified all patients with endomysial antibodies and achieved, at equal specificity, an even improved sensitivity (95.6%) as compared to EmA (91.1%) detected by the standard immunofluorescence test. Here, we have provided direct evidence that recombinant tTG is a major target of antibodies in celiac disease. Our data suggest that tTGA measured by radioligand assay have the power to overcome the limitations of the EmA-test. This new strategy may considerably facilitate large-scale screening for silent and latent celiac disease.

Genome-wide association (GWA) studies identified novel gene variants that are associated with type 2 diabetes. However, results were not always consistent across different populations. Thus, the aims of this study were (i) to replicate findings from previous GWA studies in mainly Northern European populations using data from the German KORA 500 K diabetes project and (ii) to assess the impact of BMI on associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. The KORA 500 K diabetes project includes 433 cases with validated type 2 diabetes and 1 438 nondiabetic controls from two population-based KORA surveys. Genotyping was performed using the Affymetrix GeneChip Human Mapping 500 K Array Set. We investigated associations between SNPs and type 2 diabetes in 10 genes that have been reported to increase the risk of type 2 diabetes or were in complete or near-complete linkage disequilibrium with these variants. SNPs in the CDKAL1 gene showed the strongest association with type 2 diabetes [range of age and sex-adjusted odds ratios (OR): 1.30-1.39, p-values 0.0008-0.0004]. In addition, we found evidence for association of SNPs in the genes PPARG, IGF2BP2, HHEX, TCF7L2, and FTO with type 2 diabetes in the same directions as previously described (p<0.05), but not for WFS1, CDKN2A/B, KCNJ11, or EXT2. Adjustment for BMI slightly strengthened the link between CDKAL1 and type 2 diabetes, but had almost no impact on the other associations. We conclude that gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. These associations appear to be independent of BMI.