Is There a Relationship Between Fatigue Perception and the Serum Levels of Thyrotropin and Free Thyroxine in Euthyroid Subjects?

Background: Thyrotoxicosis and hypothyroidism are associated with fatigue. Here we studied euthyroid subjects to determine if there was a relationship between serum thyrotropin (TSH), free thyroxine (FT4) and thyroperoxidase antibodies and fatigue. Methods: A total of 5897 participants of the Nijmegen Biomedical Study received a questionnaire and serum TSH (normal range 0.4-4.0 mIU/L) and FT4 (normal range 8-22 pmol/L) were measured. Fatigue was evaluated by the RAND-36 and the shortened fatigue questionnaire (SFQ). Results: Euthyroid subjects with a serum TSH level of 0.4-1.0 mIU/L had a lower RAND-36 vitality score (65.2 vs. 66.8; regression coefficient (RC) -1.6 [95% confidence interval (CI) -2.6 to -0.5]; p=0.005) and a higher SFQ score (11.7 vs. 11.0; RC 0.6 [CI 0.2-1.0]; p=0.004) than those with a TSH of 1.0-2.0 mIU/L. Those with a serum FT4 of 18.5-22 pmol/L reported fatigue more often (52.5% vs. 33.3%; relative risk (RR) 1.4 [CI 1.0-1.9]; p=0.03), had a lower RAND-36 vitality score (61.7 vs. 66.6; RC -4.4 [CI -8.1 to -0.6]; p=0.02) and a higher SFQ score (13.2 vs. 11.0; RC 1.9 [CI 0.4-3.3]; p=0.01) than subjects with a FT4 level of 11.5-15 pmol/L. In comparison to euthyroid subjects without known thyroid disease, euthyroid subjects with previously known thyroid disease reported fatigue more often (52.3% vs. 34.0%; RR 1.3 [CI 1.0-1.5]; p=0.025), had a lower RAND-36 vitality score (61.4 vs. 66.3; RC -2.9 [CI -5.3 to -0.6]; p=0.015) and a higher SFQ score (13.7 vs. 11.1; RC 1.4 [CI 0.5-2.3]; p=0.002). Conclusion: In euthyroid individuals without a history of thyroid disease, there is a modest relationship between thyroid function and fatigue with subjects having an apparently higher production of T-4 experiencing more fatigue. Subjects with a history of thyroid disease, but with normal TSH and FT4 concentrations, experience more fatigue than the general population. The reasons for this are unclear, but subtle abnormalities in the dynamics of thyroid hormone secretion should be considered.