Background: Subclinical hypothyroidism is associated with a number of cardiovascular risk factors such as hypertension, hypercholesterolemia, and diastolic dysfunction, but only limited data exist on long-term outcome of levothyroxine substitution therapy.
Objectives: To examine effects of levothyroxine substitution treatment on mortality in patients with subclinical hypothyroidism.
Study design: Historical cohort study.
Methods: Patients >18 years consulting their general practitioner from 20002009 in Copenhagen, Denmark, who underwent thyroid blood tests, were identified by individual-level linkage of nationwide registries. Only patients with subclinical hypothyroidism at baseline were included (defined as elevated TSH with normal free T4). History of thyroid disease, related medication or treatment with lithium, amiodarone, and glucocorticoids were excluded. Levothyroxine treatment was only considered if initiated within 6 months from baseline. Incidence rate ratios (IRR) of all-cause mortality were analyzed using Poisson regression models.
Results: The total cohort comprised 628 953 patients of whom 12 212 (1.9%) had subclinical hypothyroidism (mean age 55.2 (S.D. ±18.8) years; 79.8% female). Within the first 6 months, 2452 patients (20.1%) were prescribed with levothyroxine. The remaining 9760 patients (79.9%) either initiated levothyroxine therapy later than 6 months after their initial blood test or otherwise did not receive any substitution treatment at all. During a mean follow-up time of 5.0 (S.D. ±2.6) years 1566 patients died. Overall mortality rate was 26/1000 person-years (py) and 21/1000 (py) among untreated and levothyroxine treated respectively. No benefit on all-cause mortality was found in patients substituted with levothyroxine (IRR 1.02 (95% CI: 0.881.17)).
Conclusion: In patients with subclinical hypothyroidism substitution with levothyroxine is not associated with lower all-cause mortality.