Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

Mikiko Okazaki-Hada,Takumi Kudo,Akira Miyauchi,Takashi Akamizu,Mitsushige Nishikawa,Shuji Fukata,Mako Hisakado,Mitsuru Ito,Eijun Nishihara

doi:10.1530/eje-21-0584

Abstract

Resistance to thyroid hormone beta (RTHβ) is an inherited syndrome caused by mutations in the thyroid hormone receptor β (THRB) gene. Patients with RTHβ typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHβ patients and further to explore their association with THRB gene mutations. We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHβ patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHβ patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHβ. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. The frequency of AITD in male RTHβ patients was significantly higher compared to unaffected relatives. More than 20% of RTHβ patients temporarily showed laboratory findings atypical of RTHβ during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Highlights

Resistance to thyroid hormone beta (RTHβ) is an inherited condition, which was first described by Refetoff et al [1]
Mutations in the thyroid hormone receptor β (THRB) gene have been identified in the majority of patients with RTHβ, with more than 4000 patients belonging to over 600 families [2]
We found that RTHβ patients, especially men, showed a higher frequency of autoimmune thyroid disease (AITD)

Summary

Introduction

Resistance to thyroid hormone beta (RTHβ) is an inherited condition, which was first described by Refetoff et al [1]. Most studies involving a large number of patients with RTHβ originate from North America and Europe [3, 4, 5]. No studies involving a large series of patients with RTHβ have been conducted in Asian countries including Japan. Barkoff et al reported that 23.3% of patients with RTHβ had a comorbid autoimmune thyroid disease (AITD). They described that individuals with RTHβ have an increased likelihood of developing AITD [6].

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Discussion

Conclusion