Resistance to thyroid hormone (RTH) is a rare genetic disease caused by reduced tissue sensitivity to thyroid hormone. The hallmark of RTH is elevated serum levels of thyroid hormone with unsuppressed thyrotropin (TSH). The most common form of RTH results from minor defects in the ligand-binding domain of the TRb gene, resulting in impaired T3-induced transcriptional activity. This study aimed to characterize clinical and genetic features of THD suspected cases in our clinic. Eighteen patients were evaluated with THD who were admitted to our clinic with different complaints or abnormal thyroid function tests. Clinical features, biochemical and hormonal values of all cases were recorded. 7-10. Exons of THRβ gene were scanned by the Sanger sequencing method. The mean age of patients (7 males and 11 females) was 7.61 (4 days17 years and 5 months). There was at least one symptom of all patients, except 2 cases. Malnutrition and palpitation were the most common findings (8/189/18). The most frequent manifestation is not goiter incompatible with the literature (3/18). The most symptoms were 7 cases with frequent defecation, 6 cases with excessive sweating, 4 cases with short structure and 4 cases with trembling. The body mass index was <−2 S.D. in 4 cases. Neuromotor or mental retardation in 4 cases, attention and learning deficit in 2 cases, and psychosis in 1 case were the other symptoms. Thyroid autoantibodies were positive in 3 cases. In the screening of the last 4 exons of the THR1 gene, mutations were detected in 12 cases, for M313V in 3, E324K in 3, P453T in 2, R438P in one, and Phe234 silent mutations in 2 patients. Phe245 synonym mutation was present one case. THD is a dominant negative inherited disease with no phenotypic- genotype correlation. Misdiagnosis due to clinical variability is reason the wrong treatment. The clinical and genetic characteristics of pediatric18 cases were examined in this study.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology