Objective: The type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T 3 ) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2. Design and methods: A case-control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms 'rs225014' odds ratio (OR) 'thr92ala' OR 'T92A' OR 'dio2 a/g'. Results: In the case-control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (nZ173) versus 12.0% (nZ62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03-1.94, PZ0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78-2.51)), Grarup (OR 1.09 (95% CI 0.92-1.29)), and Maia (OR 1.22 (95% CI 0.78-1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03-1.36, PZ0.02). Conclusions: Our results indicate that in a case-control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a metaanalysis including 11 033 individuals, and support a role for intracellular T 3 concentration in skeletal muscle on DM2 pathogenesis.

A single nucleotide polymorphism in Type 2 deodinase (Dio2) gene (A/G) in humans, in which a threonine (Thr) changes to alanine (Ala) at codon 92 (Thr92Ala), has been associated with a lower glucose disposal rate and higher insulin resistance in type 2 diabetes (DM2) patients. 1,2 Nevertheless, these findings were not replicated in larger studies. 3,4 Recently, Gumieniak et al reported that the Ala allele increases the risk for development of arterial hypertension. 5 Since insulin resistance can cause hypertension, we sought to extend our previous original observation and evaluate the association of the Thr92Ala polymorphism with hypertension. DM2 patients were submitted to a standard questionnaire, physical examination, and laboratory tests that included Thr92Ala genotyping, as previously described. 1 Blood pressure was measured twice in the sitting position after a 10-minute rest by means of a mercury sphygmomanometer (Korotkoff phases I and V). Hypertension was defined as blood pressure Ն140/90 mm Hg or antihypertensive drug treatment. Patients with elevated serum creatinine (Ͼ1.5 mg/dL [132.6 mmol/L]) or using insulin were excluded. DNA from 315 DM2 patients was analyzed (57% women; 68% white, mean age 59 years). The genotypes were in Hardy-Weinberg equilibrium and the frequency of Ala allele (0.41) was similar to that described by Gumieniak et al. 5 Confirming our previous observation, patients homozygous for the Ala allele present higher insulin resistance than those with These apparently conflicting findings might be partially explained by differences in the studied population. In Gumieniak's report, DM2 patients were excluded and subjects were younger than those in our sample. Another major difference refers to the definition of hypertension. We used the World Health Organization definition of hypertension, and all subjects were evaluated on their regular medications. In Gumieniak's report, 5 antihypertensive medications were suspended for 2 to 4 weeks, the cut-offs for hypertension were different from the usual, and severe forms of hypertension were excluded. In conclusion, the DIO2 Thr92Ala polymorphism is associated with lower insulin sensitivity, but it is not a major determinant of blood pressure levels or hypertension in DM2 patients. Source of FundingGrant support was provided by Conselho Nacional de Desenvolvimento Científico e Technológico (CNPq), Brazil. DisclosuresNone. Luís

Objective. It is generally accepted that higher doses of radioiodine (131I) improve cure rates in Graves' disease (GD). In this trial we sought to evaluate whether very high 131I doses increase the efficacy of treatment in severe GD. Design. Clinical trial with historical control. Patients with GD and a goiter ≥48 mL were eligible for the study. The patients in the contemporaneous intervention cohort were treated with 250 μCi of 131I/mL thyroid tissue, corrected by 24-RAIU values (Group 1; n = 15). A subgroup of patients with GD and a goiter ≥48 mL who were treated with 200 μCi of 131I/mL/24-RAIU in a previously published randomized controlled trial served as a historical control group (Group 2; n = 15). The primary outcome evaluated was the one-year cure rate. Results. There were no significant baseline differences regarding age, gender, body mass index, smoking status, pretreatment with methimazole, thyroid volume, or thyroid hormone levels of the two treatment groups. The cumulative 12-month cure rate for the patients in Group 1 was 66.6%, a figure similar to the 12-month cure rate observed in Group 2 (60.0%; P = 0.99). Conclusions. Our results suggest that increasing the 131I dose does not improve cure rates in severe GD. This trial is registered with ClinicalTrials.gov NCT01039818.

Background: Thyroid cancer associated with head and neck squamous cell carcinoma (HNSCC) is rare, and management of this condition remains a matter of debate. Objectives: To report an incidentally discovered metastatic papillary thyroid carcinoma in a patient who had surgical resection of a HNSCC. We will discuss the therapeutic approach to thyroid tumors found in this circumstance. Design: A case study and a review of the literature were performed. Results: A case of incidental follicular variant papillary thyroid carcinoma found during resection for a HNSCC was studied. A series of studies indicate that the prognosis is ultimately determined by the HNSCC stage. Conclusion: Management of thyroid cancers in patients with HNSCC should be based on balance between prognoses of both neoplasms.