The syndrome of resistance to thyroid hormone (RTH) is caused by decreased tissue responsiveness to thyroid hormone. With the exception, inheritance of RTH is autosomal dominant. The receptors are encoded by two genes (THRA and THRB), each of which undergoes alternate splicing to generate receptor subtypes (TRa1, TRβ1, and TRβ2), with differing tissue distributions.Here we describe a child with novel heterozygous mutations for THRB. Nine-months-old boy presented with hyperthryoxinemia with inappropriately increased TSH levels. He had been treated with l-thyroxine under the diagnosis of congenital hypothyroidism before visiting our clinics. Goiter, growth retardation, delayed bone age, and tachycardia were absent. Alpha-subunit of thyroid hormone receptor was not elevated and TSH-secreting tumor was not found in brain MRI. TSH reponse to TRH test was exaggerated. Serum sex hormone binding globulin level was normal. Thyroid ultrasonography found no abnormality. Under the suspicion of RTH, targeted exome sequencing identified novel heterozygous mutations in THRB (c.993T>G). The mutation was not found in parents. L-thyroxine was given to patients to maintain TSH levels < 5 mIu/mL. Further studies are required to obtain long-term data on RTH.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology