Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.

Data-driven techniques have recently drawn significant interest in the predictive modeling of subcutaneous (s.c.) glucose concentration in type 1 diabetes. In this study, the s.c. glucose prediction is treated as a multivariate regression problem, which is addressed using support vector regression (SVR). The proposed method is based on variables concerning: (i) the s.c. glucose profile, (ii) the plasma insulin concentration, (iii) the appearance of meal-derived glucose in the systemic circulation, and (iv) the energy expenditure during physical activities. Six cases corresponding to different combinations of the aforementioned variables are used to investigate the influence of the input on the daily glucose prediction. The proposed method is evaluated using a dataset of 27 patients in free-living conditions. 10-fold cross validation is applied to each dataset individually to both optimize and test the SVR model. In the case where all the input variables are considered, the average prediction errors are 5.21, 6.03, 7.14 and 7.62 mg/dl for 15, 30, 60 and 120 min prediction horizons, respectively. The results clearly indicate that the availability of multivariable data and their effective combination can significantly increase the accuracy of both short-term and long-term predictions.

Objectives The relationship between thyroid dysfunction and mortality in elderly subjects is still undefined. In this population study we tested the hypothesis that in older subjects, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with increased mortality independent of potential confounders. Design Longitudinal study Setting Community-based Participants Total of 951 subjects aged 65 years and older Measurements Plasma thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations and demographic features were evaluated in participants of the Aging in the Chianti Area (InCHIANTI) study, aged 65 years or older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results A total of 819 participants were euthyroid, 83 had Subclinical hyperthyroidism (SHyper), and 29 had Subclinical hypothyroidism (SHypo). Overt Hypo- and Hyperthyroidism were found in 5 and 15 subjects, respectively. During a median of six-years of follow-up, N 210 deaths occurred (22.1 %) of which 98 (46.6%) due to cardiovascular causes. Kaplan–Meier analysis revealed higher overall mortality for SHyper (P<0.04) as compared to euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (Hazard Ratio[HR]:1.65; 95% Confidence Interval [CI]: 1.02–2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, TSH was found to be predictive of a reduced risk of all-cause mortality (HR: 0.76; 95% CI, 0.57–0.99) Conclusion SHyper is an independent risk factor for all-cause mortality in the older population. Low-normal circulating TSH should be carefully monitored in euthyroid elderly individuals.

Objectives Thyroid dysfunction in the elderly is associated with adverse clinical outcomes, with mortality being associated with low TSH. However, it is still unknown whether variability of thyroid function test within the reference range is associated with mortality in older adults. We studied the association between plasma levels of TSH, free T3 (FT3), and free T4 (FT4), and all-cause mortality in older adults who had all three hormones within the normal range. Design Longitudinal study Setting Community-based Participants Total of 815 euthyroid participants of the InCHIANTI study, aged 65 years or older Measurements All subjects had TSH, FT3, and FT4 within the reference range at baseline. Plasma TSH, FT3 and FT4 were predictors and 9-year all-cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between quartiles of TSH, FT3, and FT4 and all-cause mortality over 9 years of follow-up. Results During the follow-up (mean persons-years 8643.74 [min-max, 35.36-16985.00]), 181 deaths occurred (22.2%). Participants with TSH in the lower quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (Hazard Ratio: 2.22; 95% Confidence Interval: 1.19–4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 were associated with mortality. Conclusions In euthyroid elderly subjects, normal-low TSH represents an independent risk factor for all-cause mortality.

No abstract

BackgroundFewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown.MethodsRandomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed.ResultsBaseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers.ConclusionsV exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013

No abstract

Background: Angiosarcoma (AS) of the thyroid is a rare and aggressive tumor. Its incidence is higher in iodine-deficient areas but cases unrelated to endemic goiter have been reported.Case Presentation: We describe a case of a 63-year-old Italian man living in a non-iodine-deficient area, with no previous diagnosis of thyroid disease with a history of radiation exposure. The patient—an interventional cardiologist who had worked for 15 years in an angiographic room- came to the clinical observation because of the rapid onset of dyspnea and dysphonia. Computed tomography (CT) showed a 13-cm inhomogeneous neck mass, originating from the left thyroid lobe which caused displacement and stenosis of the trachea. The patient underwent diagnostic fine-needle aspiration that was followed by total thyroidectomy and lymphadenectomy of central and left lateral cervical nodes. The final pathological diagnosis was epithelioid angiosarcoma (EAS), high grade. The preoperative staging by CT of the head, neck, abdomen, chest and pelvis was negative. At pathological staging, the tumor was angionvasive but it was limited to the thyroid; no lymphnode metastases were detected. Chemotherapy with Epirubicin and Ifosfamide was administered for 4 cycles and, then, it was discontinued due to significant bone marrow toxicity.Conclusion: One year after diagnosis, the CT of neck, abdomen, chest, and pelvis were negative. At 2 years after diagnosis, the FDG-PET was negative with no evidence of the disease at CT Due to the known association between the occurrence of angiosarcoma after radiation therapy it is tempting to speculate that in this patient the presence of thyroid EAS may be linked to radiation exposure.The patient is still alive at 62 months after diagnosis. He is on a follow-up program by a 6-month /1-year neck, chest, abdomen, and pelvis CT evaluation with no signs of metastases.