Multiple genetic factors in the heterogeneity of thyroid hormone resistance

Roy E. Weiss, Claudio Marcocci, Gabriella Bruno-Bossio, Samuel Refetoff

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T3-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TRβ mutations have been reported. We compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T3-binding domain of TRβ; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TRβ mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T4 and T3, and rT3 levels were significantly higher in Group A vs Groups B and C. However, with the exception of T3, the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR beta mutations.

Original languageEnglish (US)
Pages (from-to)257-259
Number of pages3
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - Jan 1993
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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