Endocrine. 2026 Jun 19;91(1):210. doi: 10.1007/s12020-026-04680-x.
ABSTRACT
BACKGROUND: Thyroid hormone resistance β (RTHβ) is a rare genetic disorder characterized by reduced tissue responsiveness to thyroid hormones. This study aimed to describe the clinical, biochemical, and genetic characteristics of pediatric patients diagnosed with RTHβ.
METHODS: Children diagnosed with RTHβ were retrospectively included in the study. Clinical, biochemical, hormonal, and genetic characteristics of the patients were analyzed RESULTS: A total of 13 patients were included. The mean age at diagnosis was 8.89 ± 4.80 years. The diagnosis was established based on abnormal thyroid function tests in 53.8% of patients, family screening in 23.1%, investigation of short stature in 7.7%, and elevated TSH detected during newborn screening in 15.4%. Thyroid ultrasonography revealed no abnormalities in 77% of patients. Attention-deficit/hyperactivity disorder (ADHD) was present in 23.1% of patients, learning disabilities in 30.8%, tachycardia in 38.5%, and hypertension in 15.4%. One patient (7.7%) was receiving levothyroxine (LT4) therapy due to a prior misdiagnosis of hypothyroidism. Molecular genetic analysis identified 10 different heterozygous missense variants in the THRB gene, classified as likely pathogenic or pathogenic, one of which was novel.
CONCLUSIONS: The combination of elevated free T3 (fT3) and free T4 (fT4) levels with normal or elevated TSH should raise suspicion for RTHβ. The condition is usually asymptomatic and does not require treatment; however, misdiagnosis as hypo- or hyperthyroidism may lead to unnecessary interventions. Approximately 25-30% of patients present with ADHD and/or learning difficulties. Therefore, multidisciplinary evaluation including child psychiatry and early recognition of neurodevelopmental disorders may improve long-term outcomes.
PMID:42319533 | DOI:10.1007/s12020-026-04680-x