The FT3:FT4 ratio is not a standalone diagnostic biomarker and must be assessed alongside TSH, FT3, FT4, thyroid antibodies, glucose regulation biomarkers, and clinical presentation. An increasing ratio may be associated with emerging hypothyroidism
The reasons for an elevated FT3:FT4 ratio must be explored further to determine the clinical implications.
An increasing ratio of Free T3 to Free T4 can be associated with emerging hypothyroidism and should be assessed along with other thyroid and cardiometabolic biomarkers.
Please see the research post on FT3:FT4 https://www.optimaldx.com/research-blog/thyroid-biomarkers-free-t3-to-free-t4-ratio
Assessing FT3:FT4 may help differentiate emerging hypothyroidism from a hypothalamic-pituitary-thyroid axis response to stress. The FT3:FT4 can be higher in hypothyroidism than in stress adaptation. Evaluation of data from the Baltimore Longitudinal Study of Aging suggested that TSH of 5.2 mIU/L with an FT4 of 0.86 ng/dL (11.07 pmol/L) and FT3:FT4 ratio of 3.15 was likely associated with hypothyroidism. However, a TSH of 5.5 with a higher FT4 of 1.01 ng/dL (13 pmol/L) and a lower FT3:FT4 ratio of 2.77 or below was more likely associated with an adaptive stress response characterized by reduced deiodination of T4 to T3 (Abbey 2022).
Assessing the ratio can also help identify the cause of thyrotoxicosis when evaluating Graves’ disease versus subacute thyroiditis. In one study of 548 newly diagnosed thyrotoxicosis patients, those diagnosed with Graves’ had a significantly higher FT3:FT4 of 4.62 compared to subacute thyroiditis (2.73) or toxic adenoma/multinodular goiter (2.67). Researchers suggest a cutoff above 4.4 for differentiating Graves’ disease. Calculations were completed with FT3 in pg/mL and FT4 in ng/dL (Sriphrapradang 2016).
References
Abbey, Enoch J et al. “Free Thyroxine Distinguishes Subclinical Hypothyroidism From Other Aging-Related Changes in Those With Isolated Elevated Thyrotropin.” Frontiers in endocrinology vol. 13 858332. 4 Mar. 2022, doi:10.3389/fendo.2022.858332
Sriphrapradang C, Bhasipol A. Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine. Ann Med Surg (Lond). 2016 Aug 8;10:69-72. doi: 10.1016/j.amsu.2016.07.024. eCollection 2016 Sep.