Initial evaluation of thyroid dysfunction - Are simultaneous TSH and fT4 tests necessary?

PLoS One. 2018 Apr 30;13(4):e0196631. doi: 10.1371/journal.pone.0196631. eCollection 2018.


Objective: Guidelines for thyroid function evaluation recommend testing TSH first, then assessing fT4 only if TSH is out of the reference range (two-step), but many clinicians initially request both TSH and fT4 (one-step). Given limitations of previous studies, we aimed to compare the two-step with the one-step approach in an unselected community-dwelling study population, and develop a prediction score based on clinical parameters that could identify at-risk patients for thyroid dysfunction.

Design: Cross-sectional analysis of the population-based Busselton Health Study.

Methods: We compared the two-step with the one-step approach, focusing on cases that would be missed by the two-step approach, i.e. those with normal TSH, but out-of-range fT4. We used likelihood ratio tests to identify demographic and clinical parameters associated with thyroid dysfunction and developed a clinical prediction score by using a beta-coefficient based scoring method.

Results: Following the two-step approach, 93.0% of all 4471 participants had normal TSH and would not need further testing. The two-step approach would have missed 3.8% of all participants (169 of 4471) with a normal TSH, but a fT4 outside the reference range. In 85% (144 of 169) of these cases, fT4 fell within 2 pmol/l of fT4 reference range limits, consistent with healthy outliers. The clinical prediction score that performed best excluded only 22.5% of participants from TSH testing.

Conclusion: The two-step approach may avoid measuring fT4 in as many as 93% of individuals with a very small risk of missing thyroid dysfunction. Our findings do not support the simultaneous initial measurement of both TSH and fT4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hyperthyroidism / blood
  • Hypothyroidism / blood
  • Likelihood Functions
  • Male
  • Middle Aged
  • Reference Values
  • Retrospective Studies
  • Sensitivity and Specificity
  • Thyroid Diseases / blood*
  • Thyroid Diseases / diagnosis*
  • Thyrotropin / blood*
  • Thyroxine / blood*
  • Western Australia
  • Young Adult


  • Thyrotropin
  • Thyroxine

Grant support

The 1994/1995 Busselton Health Survey was funded by the Health Promotion Foundation of Western Australia. The current work was supported by grants from the Swiss National Science Foundation (SNSF 320030-150025 and 320030_172676 to Prof. N. Rodondi, P3SMP3-155318 and PZ00P3-167826 to Dr. T.-H. Collet). One commercial company (Diagnostic Stago) provided support in the form of salaries to Dr. P. Feddema, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is detailed in the ‘author contributions’ section.