Normal Values for the fT3/fT4 Ratio: Centile Charts (0-29 Years) and Their Application for the Differential Diagnosis of Children with Developmental Delay

Abstract

Primary congenital hypothyroidism is readily diagnosed based on elevated plasma TSH levels. In contrast, in the rare disorders of thyroid hormone resistance, TSH and often also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and has the same severe consequences for childhood development as congenital hypothyroidism. A total of 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free T3 to free T4 (fT3/fT4 ratio). The aim was to determine whether cases with genetically confirmed thyroid hormone resistance (MCT8, THRα, and SECSIBP2 defects) had an abnormal fT3/fT4 ratio. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend the use of the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be plotted on centile charts using our free online tool at http://www.thyroid-hormone-ratio.org that accepts various SI and non-SI units.