1.The role of free triiodothyronine to free thyroxine ratio in the differential diagnosis of thyrotoxicosis: A cross-sectional study
Menon Saieehwaran ; Sy Liang Yong ; Vijiya Mala Velayutham ; Jason Tan Seng Hong ; Avni Patel ; Zienna Zufida binti Zainol Rashid ; Hanisah Abdul Hamid ; Salbiah binti Mohd Isa ; Li Vern Lim
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):11-
Introduction:
Accurate diagnosis of thyrotoxicosis, a condition resulting from excessive thyroid hormone activity, is essential for
appropriate management. However, access to diagnostic tools such as thyrotropin receptor antibody (TRAb) assays
and thyroid ultrasonography remains limited in resource-constrained settings, highlighting the need for cost-effective
alternatives. Recent studies suggest that the free triiodothyronine to free thyroxine (FT3/FT4) ratio may serve as a potential
biomarker for differentiating the causes of thyrotoxicosis.
Methodology:
This cross-sectional study evaluated the FT3/FT4 ratio in newly diagnosed thyrotoxicosis patients aged ≥18 years recruited
from Hospital Tengku Ampuan Rahimah, Hospital Banting, Klinik Kesihatan Pelabuhan Klang, and Klinik Kesihatan
Pandamaran between February and December 2025. All participants underwent thyroid function testing (FT3, FT4, and
TSH) and autoantibody assessment (TRAb and anti-thyroid peroxidase [anti-TPO]). Diagnostic performance of the FT3/FT4
ratio for Graves’ disease was assessed using receiver operating characteristic (ROC) curve analysis.
Results:
Fifty-eight patients were included, of whom 58.6% were diagnosed with Graves’ disease. Patients with Graves’ disease had
significantly higher FT3 levels (median 16.8 pmol/L; IQR 10.9–25.7) compared to those with non-Graves’ thyrotoxicosis
(median 8.3 pmol/L; IQR 5.3–13.5; p <0.001), with similar trends observed for FT4 levels (p <0.001). However, the FT3/
FT4 ratio did not differ significantly between groups (p >0.05), with an overall ROC AUC of 0.572, indicating poor
discriminatory ability. Subgroup analysis based on FT4 levels improved performance; at FT4 <30 pmol/L, the FT3/FT4
ratio demonstrated 75.0% sensitivity, 91.7% specificity, and 87.5% diagnostic accuracy at a cutoff of 0.3445 (AUC = 0.813;
95% CI: 0.570–1.000; p = 0.069). No significant association was observed between the FT3/FT4 ratio and TRAb or anti-TPO.
Conclusion
The FT3/FT4 ratio has limited overall diagnostic utility but may provide adjunctive value in selected biochemical
contexts, particularly in settings with limited access to immunological testing.
Diagnosis, Differential
;
Thyroxine
;
Triiodothyronine
;
Thyrotoxicosis
;
Cross-Sectional Studies


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