title: Is there a relationship between fatigue perception and the serum levels of thyrotropin and free thyroxine in euthyroid subjects?
abstract: 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 (FT(4)) 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 FT(4) (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 FT(4) 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 FT(4) 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).
  
  
  CONCLUSIONS
  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 FT(4) 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.
authors.affiliation: Department of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. ac.ven@aig.umcn.nl
authors.forename: Annenienke C
authors.initials: AC
authors.lastname: van de Ven
authors.forename: Romana T
authors.initials: RT
authors.lastname: Netea-Maier
authors.forename: Femmie
authors.initials: F
authors.lastname: de Vegt
authors.forename: H Alec
authors.initials: HA
authors.lastname: Ross
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Ad R
authors.initials: AR
authors.lastname: Hermus
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D005221:Fatigue / Q000209:etiology*; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010465:Perception; D011795:Surveys and Questionnaires; D013959:Thyroid Diseases / Q000150:complications*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
chemical_list: D001323:Autoantibodies; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine