Serum FT3/FT4 ratio may indicate the degree of T3 compensation in congenital hypothyroidism

Background Clinical guidelines for hypothyroidism recommend measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels as diagnostic and treatment efficacy indicators. However, they do not recommend measuring serum free triiodothyronine (FT3) levels because serum FT3 levels often remain within the normal range. However, serum TSH and FT4 levels alone make diagnosis and treatment decision-making difficult in conditions such as central hypothyroidism, suggesting the need for an additional indicator distinct from serum TSH levels. We investigated whether the serum FT3/FT4 ratio could be an indicator of congenital hypothyroidism (CH) severity, instead of serum TSH level. Methods Thirty-seven newborns were diagnosed with CH (severe group (n = 13): serum TSH ≥ 30 mIU/L; moderate group (n = 24): serum TSH ≥ 5 to < 30 mIU/L). All infants in the severe group received thyroid hormone (TH) replacement therapy vs 13 infants in the moderate group (moderate group with CH). Serum TSH, FT4, FT3, and FT3/FT4 ratios were compared between each group and the two control groups of different ages at diagnosis and 2 months after treatment. Results The serum FT3/FT4 ratio was elevated before treatment compared with the control group, reflecting CH severity. Two months after TH replacement, the serum FT3/FT4 ratio decreased significantly: severe group: at diagnosis, 0.48 vs 2 months, 0.27, p =<0.0001; moderate group with TH: 0.38 vs 2 months, 0.26, p < 0.0001. No change was observed in infants without TH replacement. Discussion A high serum FT3/FT4 ratio in CH could reflect the degree of systemic T3 compensation and is an indicator of CH severity. This ratio may also be applicable in conditions in which serum TSH levels are not useful for diagnosis or when assessing treatment outcomes. Conclusion A high serum FT3/FT4 ratio may be an indicator of hypothyroidism severity.