Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese

Keisuke Kanda, Haruo Mizuno, Yukari Sugiyama, Hiroki Imamine, Hajime Togari, Kazumichi Onigata

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Loss-of-function mutations in the thyrotropin receptor (TSHR) gene were described as a syndrome characterized by thyroid hyposensivity to biologically active TSH, ranging from euthyroid to severe hypothyroidism. In Japanese, a common mutation in the TSHR gene is R450H, which demonstrated moderately impaired receptor function. We studied six subjects of Japanese origin whose major abnormality was persistent hyperthyrotropinemia by genetic sequence analysis of the TSHR gene. Three subjects were homozygous for the R450H mutation, whereas the three remaining subjects were single heterozygous. Homozygous subjects displayed mild hypothyroidism confirmed by moderately elevated basal TSH levels and excessive TSH response to TRH administration. Heterozygous subjects also demonstrated fully or partially compensated hypothyroidism, but less severe than that of homozygous subjects. More frequent involvement of the R450H mutation in the TSHR gene in Japanese was identified. In addition, a good correlation between phenotype and genotype was demonstrated in respect to biochemical analysis and drug dosage. Our observations showed clinical significance of heterozygosity associated with compensated hypothyroidism in spite of only mildly impaired receptor function.

Original languageEnglish
Pages (from-to)383-388
Number of pages6
JournalEndocrine
Volume30
Issue number3
DOIs
Publication statusPublished - 12-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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