title: A family of RTHβ with p.R316C mutation presenting occasional syndrome of inappropriate secretion of TSH.
abstract: The syndrome of inappropriate secretion of thyrotropin (SITSH) is a hallmark of resistance to thyroid hormone (RTH) due to mutations in the β isoform of the thyroid hormone receptor (TRβ). Here, we report on a family of RTH due to a TRβ mutation (RTHβ) and presenting occasional SITSH. The proband was a 16 year-old girl with a goiter, detected at a school physical examination. She was initially diagnosed as having euthyroid Hashimoto thyroiditis because her thyroid function was normal with a positive anti-thyroglobulin antibody. Follow-up examinations resulted in mild SITSH on some occasions and euthyroid on the other occasions. A magnetic resonance imaging (MRI) revealed a normal pituitary gland. Because her mother also had mild SITSH, genetic analysis was performed and revealed a heterozygous point mutation in TRβ (p.R316C). Previously, the p.R316C had only been found in severe RTH cases with homozygous mutations or with an ectopic thyroid. Her mother with a heterozygous mutation showed variable RTH phenotype on T3 suppression testing. In conclusion, the prevalence of RTHβ might be underestimated and occasional SITSH could also suggest RTHβ. TRβ gene mutation is not always correlated with the RTH phenotype.
authors.affiliation: Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ueda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tagami
authors.forename: Tamiko
authors.initials: T
authors.lastname: Tamanaha
authors.forename: Maiko
authors.initials: M
authors.lastname: Kakita
authors.forename: Kanako
authors.initials: K
authors.lastname: Tanase-Nakao
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nanba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Usui
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
mesh_terms: D000293:Adolescent; D005260:Female; D006042:Goiter / Q000235:genetics*; D006801:Humans; D009154:Mutation; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: D037042:Thyroid Hormone Receptors beta; D013972:Thyrotropin