Response to Fitzgerald et al. re: “Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status”

Dear Editor:

We thank Fitzgerald et al. ¹ for their letter and their interest in the commissioned review. ² We appreciate the authors' efforts in presenting alternative views on the use of thyrotropin (TSH) and free thyroxine (fT4) in the assessment of thyroid status in peripheral tissues. Specifically, Fitzgerald et al. propose that fT4 may be “the best single indicator of thyroid status of peripheral tissues” ¹ and provide supporting statements on the superior correlation of fT4 with clinical outcomes. They also challenge the assumption of a log–linear relationship between TSH and fT4, highlight that TSH is susceptible to change in nonthyroidal conditions, and that individual thyroid set points may be lacking.

The mandate of our writing group was to focus on the current state of practice regarding the use of TSH and fT4 in diagnosis and monitoring of thyroid disease, not to make recommendations for future thyroid testing. To the best of our knowledge, current clinical practice is still to use TSH as an initial test (Table 1), independent of combination with fT4 determination.

Thyroid research is an area of great activity and evolving evidence may offer an opportunity to reconsider existing convention, that is, based on the research cited by Fitzgerald et al. ¹ Nonetheless, any change in the clinical practice of laboratory testing for thyroid hormone status (TSH, thyroxine [T4], triiodothyronine [T3]) requires a thoughtful and systematic assessment of the evidence base and its impact on the clinical decision limits for the diagnosis, treatment, and prognosis of thyroid and related disorders. Given that fT4 assays are not well standardized and are prone to analytical interference, it would be unwise to rely on laboratory fT4 results and common fT4 cutoffs alone as the basis for clinical decisions. ³

The hypothalamus and anterior pituitary are the most sensitive tissues to changes in peripheral thyroid hormone status; hence, alterations in TSH represent the earliest biochemical manifestations of peripheral thyroid hormone dysfunction. Clinical practice supports a log–linear relationship between TSH and fT4 for the individual patient; considerations on non-log–linear relationships are also appropriate for large-scale population data. ⁴ Finally, we emphasize the judicious use of both TSH and fT4 where appropriate. Thyroid tests should be ordered by physicians experienced in interpreting results in the context of an individual patient's clinical care. Thyroid status should not be determined by biochemical parameters alone as the patient's history and clinical factors should also be considered. Hence, we do not support the notion that fT4 is single best indicator of thyroid status but advocates the appropriate consideration of both biochemical parameters, including TSH, as well as clinical assessment before therapeutic decisions are made.