SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T(4) concentration.

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IMPORTANCE Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis.OBJECTIVE To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. DESIGN, SETTING, AND PARTICIPANTSA double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017.INTERVENTIONS Levothyroxine treatment (n = 46) commencing at 25 μg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. RESULTS Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, −0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. CONCLUSIONS AND RELEVANCEIn this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction.

SCH predicted lower EPC count, which improved with T(4) treatment, independent of other CV risk factors, providing additional evidence that T(4) replacement may improve CV risk in SCH.

BackgroundCardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health.Methods/DesignThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes.ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH.Setting: Patients will be recruited from five hospitals in the North East of England.Participants: One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease.Intervention: Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo.Randomisation: Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/− 7) days of AMI.Blinding: Assignment to either the LT4 or placebo arm will be double-blinded.Outcomes: The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology.DiscussionThere is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes.Trial registrationISRCTN number: ISRCTN52505169. Date of registration: 09/01/2015

Objective: Sub-clinical hypothyroidism (SCH) is a common disorder. People with this condition may have symptoms which could affect their perception of health. Therefore, the perceived health status of people with SCH was assessed and compared with population-matched norms. Design: A prospective cross-sectional survey. Methods: Seventy-one adults with SCH, age range 18-64 years were studied. Perceived health status was measured by the Short Form-36 (SF-36) version 2 questionaire, which has been validated in a UK population setting. The SF-36 has eight scales measuring physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Their SF-36 scores were compared with UK normative data after matching for age and sex and are reported as z-scores. Results: Scores of all eight SF-36 scales were significantly lower in people with SCH compared with the normative population. A negative score (compared with zero of the normative population) indicates worse health status. The most significantly impaired aspects of health status were vitality and role limitations due to physical problems (role physical scale) with z-scores (95% confidence intervals) of 21.01 (2 0.74 to 2 1.29) and 20.73 (20.43 to 2 1.04) respectively. Thyroid autoimmunity did not influence the results. Conclusion: Perceived health status is significantly impaired in people with SCH when compared with UK normative population scores. This needs to be taken into consideration by clinicians when managing patients with this disease.European Journal of Endocrinology 152 713-717

Summary Objective B lymphocyte activating factor (BAFF), a member of the tumour necrosis factor superfamily, is essential for B cell activation, differentiation and survival. Elevated circulating BAFF levels have been found in patients with several autoimmune conditions, including Graves’ disease. In addition, BAFF gene variants have been associated with Graves’ disease in a Taiwanese cohort, and with several other autoimmune conditions in non‐Taiwanese populations. Design and methods We performed a case‐control association study to investigate two BAFF polymorphisms (rs9514828 and rs4000607) in a UK cohort of 444 patients with Graves’ disease. Genotype frequencies were compared to those from 447 local controls and more than 5000 healthy controls from the Wellcome Trust case‐control consortium (WTCCC2). Results There was a significant difference in the frequency of the AA genotype at rs4000607 between the Graves’ disease cohort and both the local controls (P = 0.045) and the WTCCC2 controls (P = 4.56 × 10−6). Furthermore, the frequency of the A allele was found to be increased in the Graves’ disease group compared to WTCCC2 controls (P = 0.02, OR 1.20 (95% CI 1.03‐1.41). No association was observed at the rs9514828 locus. Conclusion Dysfunction of the humoral immune system is an obligatory pathophysiological component of Graves’ disease, hence BAFF is an excellent functional candidate gene. We have demonstrated, for the first time, a significant association of the BAFF polymorphism rs4000607 with Graves’ disease in a UK cohort. Further work to elucidate the role of BAFF in the pathogenesis of Graves’ disease is now warranted.

Hypothyroidism affects millions of individuals in the UK and is currently a prevalent diagnosis in more than 1 in 10 individuals aged above 70 years. As the population ages this number is likely to increase. The clinical and economic effects of current management strategies for hypothyroidism, particularly in the older population, need to be evaluated.