Journal of Medical Sciences and Health Care Research
Population-Specific Reference Intervals for Serum Free Triiodothyronine (fT3) in a Conflict-Affected Population: Indirect Method Study from Syria
Abstract
Zeina Malek, Nasser Thallaj, Adnan Alkhatib, Mohmoud Elias and Ghassan Shannan
Background: Reliable interpretation of serum free triiodothyronine (fT3) depends on reference intervals reflect the population served by the reporting laboratory. Most Syrian laboratories currently apply the manufacturer’s generic euthyroid range (2.0–4.4 pg/mL), derived from Western cohorts whose nutritional, environmental, and disease profiles differ substantially from those of a population endured fourteen years of armed conflict. No population-specific fT3 reference data have been reported for Syria.
To derive age- and sex-stratified fT3 reference intervals for the Syrian population using the indirect method, to quantify the discrepancy between locally derived and manufacturer-supplied limits, and to characterise the inter-analyte correlation structure among fT3, fT4, and TSH.
Methods: Retrospective extraction of 10,020 fT3 results from a single high-throughput clinical laboratory in Damascus (January 2020–December 2024) was performed. After applying exclusion criteria, 1,999 results were eligible. Reference intervals were derived by iterative mean ± 2 SD trimming across six age–sex subgroups. All measurements were performed on the Roche cobas e 411 using the Elecsys FT3 III assay (ECLIA). Paired thyroid panels (fT3, fT4, TSH; n = 1,197) were analysed using Pearson, Spearman, and partial correlation methods.
The derived adult fT3 reference interval was 1.49–5.38 pg/mL for females and 1.32–5.70 pg/mL for males substantially wider than the manufacturer’s range, with the lower limit displaced downward by 0.51–0.68 pg/mL and the upper limit shifted upward by 0.98–1.30 pg/mL. Serum fT3 declined with age (Spearman ρ = −0.226, p < 0.001; ANOVA F = 8.88, p < 0.001), while no clinically meaningful sex difference was observed (Cohen’s d = −0.008). Among 1,197 paired panels, the fT3–fT4 Spearman correlation was ρ = 0.353 and the fT3–TSH correlation was ρ = −0.336, attenuated to −0.246 after controlling for fT4. Application of the manufacturer’s generic range would misclassify approximately 7.8% of Syrian adults as having abnormal fT3 (3.6% false-low, 4.3% false-high).
Conclusions: The manufacturer’s generic fT3 reference range misclassifies a clinically significant proportion of Syrian adults at both the hypothyroid and hyperthyroid boundaries. Adoption of the locally derived, age-stratified reference intervals reported here is recommended for Syrian laboratories using the Roche.