ESPE Abstracts

Thyroid hormone resistance (RTH) is a rare autosomal dominant genetic syndrome with a diminished response to circulating thyroid hormonesin target tissues. It has an incidence of 1:40,000-50,000, and equal sex distribution. Here we report a child with RTH, due to a mutation in THR β gene. 7 years and 5-month-old boy was referred due to thyroid hormone derangement. He was well until 3 years when he developed afebrile seizures and was on Na valproate. He was undergone brain imaging and electro encephalography which were normal. He was born to non-consanguineous parents at 33 weeks of POA with a birth weight of 2.32 kg. He had an uncomplicated post natal period. At presentation, he had no thyrotoxic symptoms, no hyperactivity or learning difficulty. On examination his weight was 20.5 kg (10^th-25^th centile), height was 121 cm(25^th-50^th centile). There was no dysmorphism or exophthalmos. He had no goitre, however he had tachycardia and hand tremors. Other system examination is unremarkable.

He was started on oral propranolol. We did family screening, and interestingly mother and one of the siblings had deranged thyroid functions. Mother was found to have a painful goitre which was recent onset, had tachycardia and no other thyrotoxic features. She was referred to adult endocrinology unit where she was started on carbimazole. The elder brother who had high T4 with unsuppressed TSH had no thyrotoxic symptoms and signs.

Genetic studies revealed that he is heterozygous for a pathogenic variant (Tyr321Cys, Y321C) in the THR β gene confirming the diagnosis of RTH. Both mother and elder sibling were also affected with the same genetic mutation. Despite this specific biochemical presentation, the resulting clinical phenotype is extremely variable. RTH should be suspected in both adults and children with elevated thyroid hormones and unsuppressed TSH. Familial occurrence of RTH has been documented in approximately 75% of cases, and 20% of the patients are de novo cases. RTH presents a unique challenge and it is mandatory to recognize it early since its diagnostic procedures, management and follow-up, differ from other forms of thyroid dysfunction.