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Research Article: Clinical manifestations of resistance to thyroid hormone beta (RTH?) syndrome in children – multicenter case series

Date Published: 2026-10-15

Abstract:
Resistance to thyroid hormone (TH) ? (RTH?) is a rare genetic disorder caused by mutations in the TH receptor ? gene ( THRB ) and characterized by elevated TH levels with non-suppressed thyroid-stimulating hormone (TSH) and variable clinical presentation. The aim of the study was to characterize the clinical and biochemical features of children with RTH?, correlate them with genetic findings and therapeutic management, to raise clinicians’ awareness of the specific characteristics of the condition. This retrospective multicenter case series included 15 children with genetically confirmed THRB variants. Clinical, laboratory, imaging, and treatment data were analyzed retrospectively. All the patients demonstrated elevated free thyroxine and free triiodothyronine concentrations with detectable, non-suppressed TSH serum level. Common findings included tachycardia (73%), neurodevelopmental disturbances (60%), and a lean phenotype (BMI <10th percentile, 53%). Misdiagnosis of primary hyperthyroidism occurred in 20% of cases. Most patients did not require pharmacological treatment or were managed with beta-blockers alone for symptomatic tachycardia control. Pediatric RTH? shows consistent biochemical features but marked clinical heterogeneity. Awareness is essential to ensure accurate diagnosis and avoid unnecessary therapy.

Introduction:
Resistance to thyroid hormone (TH) ? (RTH?) is a rare genetic disorder caused by mutations in the TH receptor ? gene ( THRB ) and characterized by elevated TH levels with non-suppressed thyroid-stimulating hormone (TSH) and variable clinical presentation. The aim of the study was to characterize the clinical and biochemical features of children with RTH?, correlate them with genetic findings and therapeutic management, to raise clinicians’ awareness of the specific characteristics of the condition.

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