Endocrine Abstracts

JOINT1866

Introduction: The clinical manifestations of resistance to thyroid hormone-β (RTH-β) can sometimes be confused with either hyperthyroidism or hypothyroidism, leading to challenges in diagnosis and treatment. In this study, we aimed to evaluate the diagnosis, treatment processes, and long-term follow-up outcomes of children with RTH-β.

Methods: A retrospective study was conducted including pediatric patients with pathogenic variants in the THRB gene and that followed up in our department for at least 6 months between 2006-2024. The physical examination, laboratory, and imaging findings at the initial presentation and the final outpatient visit were compared.

Results: Ten patients were included in the study with a median age of 4.7(min-max: 1.2-17.2) years. Weight, height, and body mass index (BMI) measurements at the first presentation were -0.4[(-2.3) – 1.5], -0.7[(-2.3) – 1.0], and 0.0[(-2.8) – 2.6] SDS, respectively. Initial evaluation showed goiter in 50%, attention deficit hyperactivity disorder and speech delay in 40%, tachycardia in 20%, and short stature in 20% of the patients. The initial TSH, freeT4, and freeT3 levels were 3.1(1.4-11.9) mIU/l, 2.3(1.3-4) ng/dl, and 7.6(4.6-9.8) ng/dl, respectively. The median time to diagnosis was 6 months. TSH receptor stimulating autoantibodies were measured in six patients. The thyroid gland volume was 1.7[(-2.5) – 6.2] SDS on the ultrasonography, and did not change significantly during the follow-up(P = 0.345). A total of five patients (50%) received treatment (three with methimazole, one with L-thyroxine, one with propranolol). TRIAC was added to the treatment in two patients. The median follow-up duration was 3.6 years, and the median age at the last visit was 11.6 years [bone age/calendar age ratio: 0.9(0.7-1.0)]. At the final evaluation, weight showed a significant increase(P = 0.028); but height and BMI were similar to the initial measurements (P = 0.203 and 0.445). At the last visit, only one patient was under LT4 treatment, and another one was receiving propranolol. Laboratory results on the last control were were similar to the initial pretreatment values; TSH 2.2 (1.1-3.8) mIU/l, freeT4 2.5 (1.4-3.6) ng/dl, and freeT3 7.0 (4.2-12.6) ng/dl (P >0.05). The serum sex hormone binding globulin level was elevated in five patients (50%).

Conclusions: Pediatric RTH-β patients were mostly misdiagnosed as hyperthyroidism leading to treatment with anti-thyroid drugs, and most individuals became treatment-free in the long-term follow-up. Also, we demonstrated that thyroid function tests and thyroid gland volume did not change with age, and growth of the children was not affected in RTH-β.

Keywords: Thyroid hormone receptor-beta, thyroid hormone metabolism disorders, Refetoff syndrome .