1 Citation (Scopus)

Abstract

Background: Pituitary resistance to thyroid hormone (PRTH) is often seen in congenital hypothyroidism (CH), presenting as elevated thyrotropin (TSH) values despite (high-)normal thyroid hormone (TH) values achieved by levothyroxine treatment. In this study, we describe a girl with CH who was referred because of difficulties interpreting thyroid function tests. She was thought to have PRTH associated with CH, but genetic studies discovered a pathogenic variant in THRB, causing resistance to TH (RTH-β). Methods: Clinical, genetic, and biochemical data of the proband's family were collected. Results: The 3-year-old girl was diagnosed with CH due to a homozygous pathogenic c.470del p.(Asn157Thrfs*3) SLC5A5 variant in the neonatal period. She needed a notably high levothyroxine dose to normalize TSH, leading to high free thyroxine levels. There were no signs of hyperthyroidism. Sequencing identified a heterozygous pathogenic c.947G>A p.(Arg316His) THRB variant. Conclusions: To our knowledge, this is the first report of concomitant SLC5A5 and THRB variants causing CH and RTH-β.

Original languageEnglish
Pages (from-to)1757-1762
Number of pages6
JournalThyroid
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Child, Preschool
  • Congenital Hypothyroidism/drug therapy
  • Consanguinity
  • Female
  • Humans
  • Pedigree
  • Symporters
  • Thyroid Hormone Receptors beta/genetics
  • Thyroid Hormone Resistance Syndrome/genetics
  • Thyroxine/therapeutic use
  • Turkey

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