Ville Langén: THYROID-STIMULATING HORMONE: REFERENCE RANGE AND RELATION TO CARDIOVASCULAR RISK

Ville Langén THYROID-STIMULATING HORMONE: REFERENCE RANGE AND RELATION TO CARDIOVASCULAR RISK University of Turku, Faculty of Medicine, Department of Internal Medicine, Doctoral Programme in Clinical Research Turku University Hospital, Heart Centre National Institute for Health and Welfare, Department of Public Health Solutions Annales Universitatis Turkuensis Painosalama Oy – Turku, Finland 2017 Thyroid dysfunctions, especially subclinical forms, are common and could be related to an elevated cardiovascular risk. Previous data on the associations of thyroid function with cardiovascular disease entities and their risk factors are conflicting and inconclusive, particularly in the area of subclinical hypoand hyperthyroidism and their clinical significance in different age groups. In addition, there has been a debate on where to set the upper limit of the thyroid-stimulating hormone (TSH) reference range, which is the cornerstone for defining the different thyroid dysfunctions. The aim of this study was to establish a new reference range for TSH and to assess the associations of TSH levels with blood pressure, lipid concentrations and cardiovascular diseases and mortality in a large, randomly selected, population-based sample of Finnish adults (N=8028). Based on our findings, we propose a new TSH reference range of 0.4–3.4 mU/L to be used for the Finnish population in laboratory units that utilise the Abbott Architect ci8200 platform. Every 1 mU/L higher concentration of TSH associated cross-sectionally with a 0.5 mmHg higher diastolic blood pressure in men but not in women. In addition, TSH values in the highest versus the lowest tertile of the reference range associated with prevalent hypertension. However, TSH did not associate longitudinally with higher blood pressure or incident hypertension over a follow-up period of 11 years. Every 1 mU/L higher level of TSH associated cross-sectionally with a 0.02 mmol/L higher concentration of low-density lipoprotein cholesterol (P=0.002). The results were essentially similar when total cholesterol, apolipoprotein B and triglyceride levels were the outcome variables. However, higher levels of TSH at baseline displayed no adverse associations with the lipid concentrations measured at the 11-year follow-up when individuals with a high-risk lipid profile at baseline were excluded from the analyses. TSH had a U-shaped association with total mortality. In addition, even subclinical form of hypothyroidism associated with the risk of sudden cardiac death. However, we could not link abnormal levels of TSH to cardiovascular disease, coronary heart disease, stroke, major adverse cardiac events or atrial fibrillation and can only speculate on the underlying mechanism of the mortality outcomes. To conclude, even subclinical hypothyroidism might be linked to an increased cardiovascular risk, but sufficiently powered randomised controlled trials are still needed to determine the cut-off levels of TSH that would indicate when different thyroid therapies should be initiated.