A rare mutation of thyroid hormone receptor beta gene in thyroid hormone resistance syndrome

Abstract

Summary

Resistance to thyroid hormone (RTH) is a rare hereditary syndrome with impaired sensitivity to thyroid hormones (TH) and reduced intracellular action of triiodothyronine (T3) caused by genetic variants of TH receptor beta ( TRB) or alpha ( TRA). RTH type beta (RTHβ) due to dominant negative variants in the TRB gene usually occurs with persistent elevation of circulating free TH, non-suppressed serum TSH levels responding to a thyrotropin-releasing hormone (TRH) test, an absence of typical symptoms of hyperthyroidism and goiter. Here, we present a rare variant in the TRB gene reported for the first time in an Italian patient with generalized RTHβ syndrome. The patient showed elevated TH, with non-suppressed TSH levels and underwent thyroid surgery two different times for multinodular goiter. The genetic test showed a heterozygous mutation in exon 9 of the TRB gene resulting in the replacement of threonine (ACG) with methionine (ATG) at codon 310 (p.M310T). RTHβ syndrome should be considered in patients with elevated TH, non-suppressed TSH levels and goiter.

Learning points

• Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary syndrome with impaired tissue responsiveness to thyroid hormones (TH).

• Diagnosis of RTH is usually based on the clinical finding of discrepant thyroid function tests and confirmed by a genetic test.

• RTH is a rare condition that must be considered for the management of patients with goiter, elevation of TH and non-suppressed serum TSH levels in order to avoid unnecessary treatments.