Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. Iodine nutrition is a key determinant of thyroid disease risk; however, other factors, such as ageing, smoking status, genetic susceptibility, ethnicity, endocrine disruptors and the advent of novel therapeutics, including immune checkpoint inhibitors, also influence thyroid disease epidemiology. In the developed world, the prevalence of undiagnosed thyroid disease is likely falling owing to widespread thyroid function testing and relatively low thresholds for treatment initiation. However, continued vigilance against iodine deficiency remains essential in developed countries, particularly in Europe. In this report, we review the global incidence and prevalence of hyperthyroidism and hypothyroidism, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data. We also highlight the pressing need for detailed epidemiological surveys of thyroid dysfunction and iodine status in developing countries.

IMPORTANCE Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm. OBJECTIVE To define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52 298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine. MAIN OUTCOMES AND MEASURES The median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy. RESULTS Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had increased odds of developing a suppressed thyrotropin level, whereas individuals with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus, hypertension, and raised lipid levels) did not. CONCLUSIONS AND RELEVANCE We observed a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism and a substantial risk of developing a suppressed thyrotropin level following therapy. Large-scale prospective studies are required to assess the risk-benefit ratio of current practice.

The management of primary hypothyroidism with levothyroxine (L-T4) is simple, effective and safe, and most patients report improved well-being on initiation of treatment. However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction. The management of such individuals has been the subject of controversy and of considerable public interest. The American Thyroid Association (ATA) and the European Thyroid Association (ETA) have recently published guidelines on the diagnosis and management of hypothyroidism. These guidelines have been based on extensive reviews of the medical literature and include sections on the role of combination therapy with L-T4 and liothyronine (L-T3) in individuals who are persistently dissatisfied with L-T4 therapy. This position statement by the British Thyroid Association (BTA) summarises the key points in these guidelines and makes recommendations on the management of primary hypothyroidism based on the current literature, review of the published positions of the ETA and ATA, and in line with best principles of good medical practice. The statement is endorsed by the Association of Clinical Biochemistry, (ACB), British Thyroid Foundation, (BTF), Royal College of Physicians (RCP) and Society for Endocrinology (SFE).

Summary Background:  Patients with diabetes mellitus are at an increased risk of thyroid disease. The frequency of thyroid dysfunction in diabetic patients is higher than that of the general population and up to a third of patients with type‐1 diabetes (T1DM) ultimately develop thyroid dysfunction. Unrecognised thyroid dysfunction may impair metabolic control and add to cardiovascular disease risk in diabetic patients. Aims:  Our aims were to review the current literature on the association between thyroid dysfunction and diabetes mellitus, to highlight relevant clinical implications, and to examine present thyroid disease screening strategies in routine diabetes care. Results:  The pleiotropic effects of thyroid hormones on various metabolic processes are now better understood. Uncontrolled hyperthyroidism in diabetic patients may trigger hyperglycaemic emergencies while recurrent hypoglycaemic episodes have been reported in diabetic patients with hypothyroidism. Furthermore, thyroid dysfunction may amplify cardiovascular disease risk in diabetic patients through inter‐relationships with dyslipidaemia, insulin resistance and vascular endothelial dysfunction. However, the significance of subclinical degrees of thyroid dysfunction remains to be clarified. While these developments have implications for diabetic patients a consensus is yet to be reached on optimal thyroid screening strategies in diabetes management. Conclusions:  The increased frequency of thyroid dysfunction in diabetic patients and its likely deleterious effects on cardiovascular and metabolic function calls for a systematic approach to thyroid disease screening in diabetes. Routine annual thyroid testing should be targeted at diabetic patients at risk of thyroid dysfunction such as patients with T1DM, positive thyroid autoantibodies or high‐normal TSH concentrations.

Background: Although the detrimental effects of severe iodine deficiency are well recognised, the benefits of correcting mild-to-moderate iodine deficiency are uncertain. Objectives: We undertook a systematic review of the impact of iodine supplementation in populations with mildto-moderate iodine deficiency. Methods: We searched Medline and the Cochrane library for relevant articles published between January 1966 and April 2013, which investigated the effect of iodine supplementation on maternal and newborn thyroid function, infant neurodevelopment and cognitive performance in school-age children. The quality of studies was graded and eligible trials were evaluated in the meta-analysis. Results: Nine randomised controlled trials (RCTs) and eight observational studies met the inclusion criteria. Controlled trials on infant neurodevelopment were lacking; gestational iodine supplementation reduced maternal thyroid volume and serum thyroglobulin and in some studies prevented a rise in serum thyroid-stimulating hormone. None of the intervention trials recorded an excess frequency of thyroid dysfunction in contrast to observational studies. A pooled analysis of two RCTs which measured cognitive function in school-age children showed modest benefits of iodine supplementation on perceptual reasoning (standardised mean difference (SMD) 0.55; 95% CI 0.05, 1.04; PZ0.03) and global cognitive index (SMD 0.27; 95% CI 0.10, 0.44; PZ0.002) with significant heterogeneity between studies. Conclusion: Iodine supplementation improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children, even in marginally iodine-deficient areas. Further large prospective controlled studies are urgently required to clarify these findings and quantify the risk/benefits of iodine supplementation in regions previously believed to be iodine sufficient such as the UK.

The majority of levothyroxine-treated women have early gestational TSH levels above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of thyroid hormone replacement in early pregnancy.

BACKGROUND: Graves' disease is routinely treated with antithyroid drugs (ATD), radioactive-iodine (RAI), or surgery but it is uncertain whether the choice of initial therapy influences long-term outcomes. We evaluated cardiovascular morbidity and mortality according to the modality and effectiveness of primary therapy in Graves' disease. METHODS: The study was conducted through linked datasets within the All-Wales Secure Anonymised Information Linkage (SAIL) Databank. Graves' disease patients were identified from a regional TSH-receptor-antibody test register, (n=4,189, female 82%, 1998-2013) and matched by age and sex to a control population in SAIL (n=16,756). Patients were grouped by treatment within one-year of diagnosis as: (1) ATD (n=3587), (2) RAI with resolved hyperthyroidism (RAI-Group-A, n=250), and (3) RAI with unresolved hyperthyroidism (RAI-Group-B, n=182). One-year landmark Kaplan-Meier and Cox regression models were used to analyse the association of treatment with all-cause mortality and major adverse cardiovascular events (MACE, myocardial infarction, heart failure, ischaemic stroke, or death). The relationship between FT4 concentration and outcomes was analysed using restricted cubicspline regression models. FINDINGS: Overall, patients had increased mortality compared to controls (HR 1•23, 95%CI 1•06, 1•42). Compared to ATD-treated patients, mortality was reduced in RAI-Group-A (HR 0•50, 95%CI 0•29, 0•85) but not RAI-Group-B (HR 1•51, 95%CI 0•96, 2•37). Persistently low-TSH at 1-year was associated with increased mortality independent of treatment modality (HR 1•55, 95%CI 1•08-2•24). Spline-regressions demonstrated a positive non-linear relationship between 1-year-FT4 and outcomes.

These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.