Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the Thyroid Events Amsterdam (THEA) score

Arch Intern Med. 2008 Aug 11;168(15):1657-63. doi: 10.1001/archinte.168.15.1657.


Background: Genetic and environmental factors are involved in the pathogenesis of autoimmune thyroid disease (AITD). Family members of patients with AITD are at increased risk for AITD, but not all will develop overt hypothyroidism or hyperthyroidism. Our goal was to develop a simple predictive score that has broad applicability and is easily calculated at presentation for progression to overt hypothyroidism or hyperthyroidism within 5 years in female relatives of patients with AITD.

Methods: We conducted a prospective observational cohort study of 790 healthy first- or second-degree female relatives of patients with documented Graves or Hashimoto disease in The Netherlands. Baseline assessment included measurement of serum thyrotropin (TSH), free thyroxine (FT(4)), and thyroid peroxidase (TPO) antibody levels as well as evaluation for the presence and levels of Yersinia enterocolitica antibodies. We also gathered data on family background, smoking habits, use of estrogen medication, pregnancy, and exposure to high levels of iodine. In follow-up, thyroid function was investigated annually for 5 years. As main outcome measures, termed events, we looked for overt hypothyroidism (TSH levels >5.7 mIU/L and FT(4) levels <0.72 ng/dL) or overt hyperthyroidism (TSH levels <0.4 mIU/L and FT(4) levels >1.56 ng/dL).

Results: The cumulative event rate was 7.5% over 5 years. The mean annual event rate was 1.5%. There were 38 hypothyroid and 13 hyperthyroid events. Independent risk factors for events were baseline findings for TSH and TPO antibodies in a level-dependent relationship (for TSH the risk already starts to increase at values >2.0 mIU/L) and family background (with the greatest risk attached to subjects having 2 relatives with Hashimoto disease). A numerical score, the Thyroid Events Amsterdam (THEA) score, was designed to predict events by weighting these 3 risk factors proportionately to their relative risks (maximum score, 21): low (0-7), medium (8-10), high (11-15), and very high (16-21). These THEA scores were associated with observed event rates of 2.7%, 14.6%, 27.1%, and 76.9%, respectively.

Conclusions: An accurate simple predictive score was developed to estimate the 5-year risk of overt hypothyroidism or hyperthyroidism in female relatives of patients with AITD. However, in view of the small number of observed events, independent validation of the THEA score is called for.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / blood
  • Disease Progression
  • Family
  • Female
  • Graves Disease / genetics*
  • Hashimoto Disease / genetics*
  • Humans
  • Hyperthyroidism / genetics*
  • Hypothyroidism / genetics*
  • Iodide Peroxidase / immunology
  • Logistic Models
  • Netherlands
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Thyrotropin / blood
  • Thyroxine / blood
  • Yersinia enterocolitica / immunology


  • Antibodies
  • Thyrotropin
  • Iodide Peroxidase
  • Thyroxine