Abstract
Autoimmune thyroiditis resulting in hypothyroidism is a gradual destructive process. It is postulated that in the early stages of disease, thyroid-stimulating hormone (TSH) concentrations may be within the reference range. Equally, in early stages of disease processes resulting in hyperthyroidism, the concentration of TSH could decrease, but remain within the reference range. In this longitudinal population-based study, 15106 participants were followed up after 11 years to assess their risk of developing thyroid dysfunction based on their baseline TSH concentration.
Baseline thyroid disease was excluded by self-reporting and exclusion of TSH results either outside the reference range or with a matched low free thyroxine (T4) concentration. Baseline and follow-up TSH was measured by the Delfia hTSH Ultra and Abbott Architect ci8200, respectively. Thyroid disease at follow-up was established by self-reporting, the presence of biochemical hypothyroidism or hyperthyroidism, or evidence of being prescribed levothyroxine or thionamides as per the Norwegian prescription database.
The risk of hypothyroidism increased with increasing baseline TSH concentration. In women, the odds ratio for development of future hypothyroidism was 2.3 (95% CI 1.5–3.3) with a baseline TSH of 1.5–1.9 mU/L, 8.4 (95% CI 5.7–12.3) with a baseline TSH of 2.5–2.9 mU/L and 43.4 (95% CI 27.8–67.7) with a baseline TSH of 4.0–4.5 mU/L compared with women with a baseline TSH of 0.5–1.4 mU/L. In men, the association was similar, but at a given TSH, the risk was lower. The risk of hyperthyroidism was higher in women with a baseline TSH of 0.2–0.49 mU/L (odds ratio 2.9) compared with women with a baseline TSH ≥0.5 mU/L.
Limitations of the study include the probable inclusion of subclinical and iatrogenic hypothyroid patients in the hypothyroidism outcome group. In view of biological variation, using an average baseline TSH concentration and also including thyroid autoantibodies may alter risk prediction.
In summary, a TSH concentration within accepted normal reference limits is associated with a risk of developing future hypothyroidism and possibly hyperthyroidism.