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

Abstract

Objective 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. Design and methods 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. Results 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. Conclusions 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.

Advances in Thyroid Function Tests: Precision Diagnostics and Clinical Implications

“…Integrating molecular diagnostics with imaging modalities improves the accuracy of diagnosing and characterizing thyroid problems. Ultrasound imaging is a critical component in the evaluation of thyroid nodules [ 17 ]. The use of molecular testing in conjunction with ultrasound findings facilitates a more precise risk assessment, enabling differentiation between benign and malignant nodules.…”

“…The use of molecular testing in conjunction with ultrasound findings facilitates a more precise risk assessment, enabling differentiation between benign and malignant nodules. The utilization of this comprehensive methodology assists healthcare professionals in making well-informed judgments about the necessity of additional diagnostic procedures or surgical intervention [ 17 ].…”

“…Identifying supplementary genetic markers and comprehending their functional implications can facilitate the development of more precise and individualized strategies for diagnosis and therapy. Investigating innovative indicators beyond conventional thyroid hormones represents a potentially fruitful direction [ 17 ]. Proteomic and metabolomic studies can reveal distinct signatures linked to thyroid dysfunction, offering supplementary information layers to facilitate a more thorough evaluation [ 28 ].…”