Resistance to Thyroid Hormone Due to a Novel Thyroid Hormone Receptor Mutant in a Patient with Hypothyroidism Secondary to Lingual Thyroid and Functional Characterization of the Mutant Receptor

Abstract

This is the first reported case of a R316C TR mutation. The characteristics of the R316C mutant differed from those of the R316H mutant. Our findings suggest that R316C causes reduced association with and impaired release of NCoR, resulting in RTH predominantly at the pituitary level, and that slightly elevated serum TSH level with high dose of levothyroxine might be optimum for normal growth.

Coexistence of resistance to thyroid hormone and ectopic thyroid: ten-year follow-up

“…The coexistence of RTH and ectopic thyroid is extremely rare and is difficult to distinguish, three cases have been reported (12)(13)(14). Here we describe an unusual patient with RTH and ectopic thyroid.…”

“…LT-4 supplementation was necessary to the RTH patients with hypothyroidism (18)(19)(20). While other patients with RTH rarely require treatment, treatment is clearly necessary in the patient due to the high concentrations of TSH, which may cause further expansion of the lingual thyroid tissue (21).…”

A family of RTHβ with p.R316C mutation presenting occasional syndrome of inappropriate secretion of TSH

“…1A and 1B). The molecular characteristics of p.R316C were compared with a common mutant, p.R316H, using in vitro studies by Nakajima et al [7]. The binding of p.R316C to T3 was significantly decreased to 38% that of the wild type.…”

“…Nakajima Y et al [7] reported a case of RTHβ due to a novel sporadic mutation, the arginine to cysteine in the codon 316 of TRβ gene (p.R316C), in 2010. The patient was a newborn with a heterozygous p.R316C mutation.…”

Growth and Development in a Child With Resistance to Thyroid Hormone and Ectopic Thyroid Gland

“…5 Key features are high serum-free T4 in the presence of nonsuppressed TSH and without the typical symptoms and metabolic consequences of thyroid hormone excess. 6 The combination of RTH and CH has rarely been reported, 7,8 but persistent elevation of TSH during CH treatment is well recognized. Where noncompliance has been excluded, it is generally attributed to altered thyrotroph set point.…”