Introduction
Thyroid hormones are produced in response of the thyroid gland to thyroid stimulating hormone (TSH) secreted from anterior pituitary gland. Circulating thyroid hormones in forms of T4 and T3 enter cells by diffusion and, in some tissues, such as the thyroid and brain, by active transport [1]. T3 is the active form of thyroid hormones which will also be available to cells from local conversion of T4 into T3 in side cells them self. This locally produced T3 can leave the cell and binds to T3 receptors in other tissues. In humans, approximately 80 percent of extrathyroidal T3 produced from T4 is produced intracellularly [2,3]. Intracellular T3 binds to nuclear receptor called Thyroid Receptor (TR). T3-TR complexes then bind to regulatory regions contained in the genes that are responsive to thyroid hormone and exerts its action [4].
There are two TRs, alpha (THRa) and beta (THRb) [4,5]. THRa is mainly found in bones, intestine nervous system and heart while THRb is found mainly in retina, ear, heart, nervous system and it’s the main regulator of the negative feedback on pituitary thyroid axis [6].
Most patients diagnosed with RTH are found to have mutations in THRb with variant mutations had been described. However, recently some patients are found to have mutations in THRa [6]. Clinical manifestation depends on the receptor affected and the magnitude of the resistance. There is no specific treatment for RTH and multiple modalities of treatment have been found in reviewing the literature.
In this article we are reporting case of RTH, confirmed with genetic testing and found to have sequence variant mutation that is not well described due to absence of genetic conclusive evidence.