For patients taking thyroxine replacement guidelines generally recommend aiming for a target TSH within the laboratory reference range. The evidence for this guidance is generally based on an extrapolation of data from patients with endogenous subclinical thyroid disease. We aimed to examine the safety of having a TSH which was either suppressed (≤0.03 mU/l), low (0.040.4 mU/l), normal (0.44.0 mU/l) or raised (>4.0 mU/l) in a population-based cohort of patients all of whom were treated with thyroxine.
We used a population-based thyroid register (TEARS) linked to outcomes data from hospitalisation records, death certification data and other datasets between 1993 and 2001. The endpoints of cardiovascular disease, dysrhythmias and fractures were assessed. Patients were categorised, using a time weighted mean of all TSH recordings.
There were a total of 16 426 patients on thyroxine replacement (86% female, mean age 60 years) with a total follow-up of 74 586 years. Cardiovascular disease, dysrhythmias and fractures were increased in patients with a high TSH (adjusted hazards ratio 1.95 (1.732.21), 1.80 (1.332.44) and 1.83 (1.412.37) respectively), and patients with a suppressed TSH (1.37 (1.171.6), 1.6 (1.12.33) and 2.02 (1.552.62) respectively), when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes (HR: 1.1 (0.991.123), 1.13 (0.881.47) and 1.13 (0.921.39) respectively.
People on long-term thyroxine with a high or suppressed TSH are at increased risk of cardiovascular disease, dysrhythmias and fractures. People with a low but not suppressed TSH did not have an increased risk of these outcomes in this study. It may be safe for patients treated with thyroxine to have a low but not suppressed serum TSH concentration.