A novel thyroid hormone receptor-beta mutation, not anticipated to occur in resistance to thyroid hormone, causes variable phenotypes

B. Catargi, M. Monsaingeon, V. Bex-Bachellerie, N. Ronci-Chaix, H. Trouette, A. Margotat, A. Tabarin, P. Beck-Peccoz

Research output: Contribution to journalArticlepeer-review


Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-β (TRβ) gene. We report here for the first time in vivo the mutation R429W (CCG→TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T3 -binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the propositus and his grandmother had an authentic hyperthyroidism with high FT4 plasma level in the presence of inappropriate TSH. On the other hand, spontaneous variations of clinical features and -interestingly - of plasma FT4 concentrations with time in the propositus, and the phenotype observed in his mother who never complained with thyrotoxic symptoms, confirmed the in vitro binding and functional predictions. The most intriguing is the clinical course of the grandmother as she first presented with predominant pituitary RTH and a diffuse goiter and finally with a toxic multinodular goiter with normal T3 and T4 plasma concentrations and suppressed TSH. In conclusion, we report a novel mutation in the gene encoding the thyroid hormone receptor responsible for predominant pituitary RTH already described in vitro but not in vivo. The fluctuant phenotype of the propositus suggests that other factors modulate the degree of tissue resistance that is under genetic control. Toxic multinodular goiter, possibly due to chronic TSH stimulation during RTH, in addition to the phenotype variability, increases the difficulty to diagnose this thyroid disorder.

Original languageEnglish
Pages (from-to)137-142
Number of pages6
JournalHormone Research
Issue number3-4
Publication statusPublished - 2002


  • Hyperthyroidism
  • Resistance to thyroid hormone
  • Thyroid
  • Thyroid hormone receptor-beta

ASJC Scopus subject areas

  • Endocrinology


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