title: Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients.
abstract: OBJECTIVE
  The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but also self-reported stress. We tested the hypothesis whether advancing age is associated with less exposure to stress, resulting in a lower immunological response, and less severe Graves' hyperthyroidism.
  
  
  METHODS
  Cross-sectional multicenter study.
  
  
  METHODS
  Two hundred and sixty-three consecutive untreated patients with a first episode of Graves' hyperthyroidism were included. The severity of Graves' hyperthyroidism was evaluated biochemically (freeT(4)-index and freeT(3)-index, thyrotropin-binding inhibitory immunoglobulin (TBII)) and clinically by the hyperthyroid symptom scale score (HSS score). Stress exposure was quantitated by three questionnaires.
  
  
  RESULTS
  Advancing age was associated with less severe Graves' hyperthyroidism, both biochemically by lower serum freeT(3)-index and freeT(4)-index (P<0.01), lower serum TBII (P=0.05), and clinically by lower HSS scores (P=0.04) and smaller goiter size (P<0.01). FreeT(3)-index and freeT(4)-index were directly associated with HSS scores (P<0.01). Stress scores were associated with HSS scores (P<0.01) but not with biochemical severity of Graves' hyperthyroidism. Advancing age was associated with lower scores for stress exposure. Multivariate regression analysis showed that HSS score was independently related to the tendency to report negative feelings (P<0.01) but not to other stress scores and also not to age.
  
  
  CONCLUSIONS
  Advancing age is associated with less exposure to stress, lower serum TBII and less severe clinical and biochemical Graves' hyperthyroidism. Because no direct relationship exists between stress exposure and TBII or freeT(3)-index and freeT(4)-index, we reject our hypothesis that less stress is causally related to biochemically less severe Graves' hyperthyroidism in old age. HSS score is primarily determined by negative feelings and not by age.
authors.affiliation: Department of Endocrinology and Metabolism, F5-161, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. x.g.vos@amc.nl
authors.forename: Xander G
authors.initials: XG
authors.lastname: Vos
authors.forename: Natalie
authors.initials: N
authors.lastname: Smit
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Jos F
authors.initials: JF
authors.lastname: Brosschot
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006111:Graves Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D013315:Stress, Psychological / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D011795:Surveys and Questionnaires; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: D014284:Triiodothyronine; D013974:Thyroxine