Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family

Aksoy D., Gurlek A., Ringkananont U., Weiss R., Refetoff S.

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol.28, no.4, pp.379-383, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 4
  • Publication Date: 2005
  • Doi Number: 10.1007/bf03347207
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.379-383
  • Hacettepe University Affiliated: Yes


The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T-3)-binding domain of the TR beta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T-3 to 17% of that of the normal TR beta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T-4 and T-3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TR beta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered. (c) 2005, Editrice Kurtis.