Thyroid Hormone Receptor Beta Gene Mutation (P453A) in a Family Producing Resistance to Thyroid Hormone

Background: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome characterized by decreased responsiveness of target tissues to thyroid hormone. Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH). Methods: The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as having multinodular toxic goiter which was treated with antithyroid drugs and partial thyroidectomy. Her younger son had attention deficit hyperactivity disorder and primary encopresis, but normal intellectual quotient. Both had elevated serum iodothyronine levels with nonsuppressed thyrotropin. Results: A mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of RTH. Conclusion: Mutational analysis of the TR beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing.