Resistance to
thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to
thyroid hormone (TH). Its characteristics are a high level of TH and inappropriate lack of TSH suppression. RTH is mainly categorized as generalized RTH (GRTH), pituitary RTH (PRTH), and peripheral tissue RTH (PTRTH). Untreated subjects with GRTH usually achieve a normal metabolic state. We describe a 21-year-old Japanese woman with GRTH and coincidental
chronic thyroiditis. Physical examination revealed palpable
goiter,
congenital alopecia on top of the head, and short stature. She showed elevated levels of free
triiodothyronine (FT3) and free
thyroxine (FT4), and an inappropriately normal level of TSH.
Anti-thyroglobulin and anti-
thyroid peroxidase antibodies were positive. A TRH stimulation test showed a normal TSH response. The patient received the standardized diagnostic protocol, administration of incremental doses of
liothyronine (L-T3). The peak TSH level after the TRH stimulation test gradually decreased. The patient showed low sensitivity to TH in terms of bone metabolism,
protein catabolism, lipid metabolism, and urine
magnesium metabolism. Sequence analysis of the TR beta gene was performed with informed consent, and this revealed a novel heterozygous mutation at
codon 347 resulting in a GGG (
glycine) to GCG (
alanine) substitution (G347A). The patient was diagnosed as having GRTH with
chronic thyroiditis, and carrying a novel mutation, G347A, of the TR beta gene.