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J Clin Endocrinol Metab. 2012 Jan;97(1):93-9. doi: 10.1210/jc.2011-1724. Epub 2011 Nov 2.

Serum TSH within the reference range as a predictor of future hypothyroidism and hyperthyroidism: 11-year follow-up of the HUNT Study in Norway.

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  • 1Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Postboks 8905 MTFS, N-7491 Trondheim, Norway.



Serum TSH in the upper part of the reference range may sometimes be a response to autoimmune thyroiditis in early stage and may therefore predict future hypothyroidism. Conversely, relatively low serum TSH could predict future hyperthyroidism.


The objective of the study was to assess TSH within the reference range and subsequent risk of hypothyroidism and hyperthyroidism.


This was a prospective population-based study with linkage to the Norwegian Prescription Database.


A total of 10,083 women and 5,023 men without previous thyroid disease who had a baseline TSH of 0.20-4.5 mU/liter and who participated at a follow-up examination 11 yr later.


Predicted probabilities of developing hypothyroidism or hyperthyroidism during follow-up, by categories of baseline TSH, were estimated.


During 11 yr of follow-up, 3.5% of women and 1.3% of men developed hypothyroidism, and 1.1% of women and 0.6% of men developed hyperthyroidism. In both sexes, the baseline TSH was positively associated with the risk of subsequent hypothyroidism. The risk increased gradually from TSH of 0.50-1.4 mU/liter [women, 1.1%, 95% confidence interval (CI) 0.8-1.4; men, 0.3%, 95% CI 0.1-0.6] to a TSH of 4.0-4.5 mU/liter (women, 31.5%, 95% CI 24.6-39.3; men, 14.7%, 95% CI 7.7-26.2). The risk of hyperthyroidism was higher in women with a baseline TSH of 0.20-0.49 mU/liter (3.9%, 95% CI 1.8-8.4) than in women with a TSH of 0.50-0.99 mU/liter (1.4%, 95% CI 0.9-2.1) or higher (∼1.0%).


TSH within the reference range is positively and strongly associated with the risk of future hypothyroidism. TSH at the lower limit of the reference range may be associated with an increased risk of hyperthyroidism.

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