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

Nina-Maria Wilpert1,2,3, Roma Thamm4, Michael Thamm4

  • 1NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, D-10117 Berlin, Germany.

International Journal of Molecular Sciences
|August 29, 2024
PubMed

Insights

Thyroid hormone resistance, unlike congenital hypothyroidism, often shows normal TSH levels. This study found the free T3/T4 ratio effectively screens for thyroid hormone resistance in children with developmental delays.

Area of Science:

  • Endocrinology
  • Genetics
  • Pediatrics

Background:

  • Primary congenital hypothyroidism is diagnosed by elevated thyroid-stimulating hormone (TSH).
  • Thyroid hormone resistance (THR) presents with normal TSH and thyroid hormone levels, posing diagnostic challenges.
  • THR, caused by defects in hormone metabolism, transport, or receptor activation, can impair child development.

Purpose of the Study:

  • To establish normal sex-specific percentiles for the free triiodothyronine (fT3) to free thyroxine (fT4) ratio (fT3/fT4).
  • To assess if the fT3/fT4 ratio can differentiate children with genetically confirmed THR (MCT8, THRα, SECISBP2 defects) from controls.
  • To evaluate the fT3/fT4 ratio as a screening tool for identifying THR syndromes in children with developmental delay.

Main Methods:

  • Generated normal values and sex-specific percentiles for the fT3/fT4 ratio using 23,522 data points from children and young adults.
  • Analyzed fT3/fT4 ratios in individuals with developmental delay and confirmed genetic defects in MCT8, THRα, and SECISBP2.
  • Compared patient fT3/fT4 ratios with those from normal controls and pathological controls, including children with severe cerebral palsy.

Main Results:

  • Demonstrated a clear separation of fT3/fT4 ratio values between patients with THR and control groups.
  • Established normative data and sex-specific percentiles for the fT3/fT4 ratio.
  • Identified the fT3/fT4 ratio as a sensitive indicator for thyroid hormone resistance.

Conclusions:

  • The fT3/fT4 ratio effectively distinguishes individuals with thyroid hormone resistance from normal and other pathological conditions.
  • Recommends the fT3/fT4 ratio as a practical screening parameter for identifying thyroid hormone resistance syndromes in children with developmental delay.
  • An online tool is available for plotting fT3/fT4 ratios on centile charts for clinical use.

Keywords:
MCT8 deficiencySECISBP2 mutationsSLC16A2 mutationsTHRA mutationsTSHfT3/fT4 ratioperipheral thyroid hormone resistancereference valuesthyroid hormone

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