Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene

Haruo Mizuno, Keisuke Kanda, Yukari Sugiyama, Hiroki Imamine, Tetsuya Ito, Ineko Kato, Hajime Togari, Tomohiro Kamoda, Kazumichi Onigata

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.

Original languageEnglish
Pages (from-to)318-323
Number of pages6
JournalHormone Research
Volume71
Issue number6
DOIs
Publication statusPublished - 01-06-2009
Externally publishedYes

Fingerprint

Thyrotropin Receptors
Mutation
Genes
Thyroid Hormones
Hormone Replacement Therapy
Hypothyroidism
Intelligence
Thyroxine
Thyroid Gland
Reference Values
Newborn Infant
Phenotype
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Mizuno, H., Kanda, K., Sugiyama, Y., Imamine, H., Ito, T., Kato, I., ... Onigata, K. (2009). Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene. Hormone Research, 71(6), 318-323. https://doi.org/10.1159/000223415
Mizuno, Haruo ; Kanda, Keisuke ; Sugiyama, Yukari ; Imamine, Hiroki ; Ito, Tetsuya ; Kato, Ineko ; Togari, Hajime ; Kamoda, Tomohiro ; Onigata, Kazumichi. / Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene. In: Hormone Research. 2009 ; Vol. 71, No. 6. pp. 318-323.
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abstract = "Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.",
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Mizuno, H, Kanda, K, Sugiyama, Y, Imamine, H, Ito, T, Kato, I, Togari, H, Kamoda, T & Onigata, K 2009, 'Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene', Hormone Research, vol. 71, no. 6, pp. 318-323. https://doi.org/10.1159/000223415

Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene. / Mizuno, Haruo; Kanda, Keisuke; Sugiyama, Yukari; Imamine, Hiroki; Ito, Tetsuya; Kato, Ineko; Togari, Hajime; Kamoda, Tomohiro; Onigata, Kazumichi.

In: Hormone Research, Vol. 71, No. 6, 01.06.2009, p. 318-323.

Research output: Contribution to journalArticle

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T1 - Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene

AU - Mizuno, Haruo

AU - Kanda, Keisuke

AU - Sugiyama, Yukari

AU - Imamine, Hiroki

AU - Ito, Tetsuya

AU - Kato, Ineko

AU - Togari, Hajime

AU - Kamoda, Tomohiro

AU - Onigata, Kazumichi

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N2 - Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.

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