Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene.
OBJECTIVE
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.
Mizuno
Haruo
H
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hamizuno@med.nagoya-cu.ac.jp
Kanda
Keisuke
K
Sugiyama
Yukari
Y
Imamine
Hiroki
H
Ito
Tetsuya
T
Kato
Ineko
I
Togari
Hajime
H
Kamoda
Tomohiro
T
Onigata
Kazumichi
K
D000293:Adolescent; D019943:Amino Acid Substitution; D044466:Asian People; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006720:Homozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000235:genetics*; D007564:Japan; D008297:Male; D020125:Mutation, Missense; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood / Q000627:therapeutic use; D013974:Thyroxine / Q000627:therapeutic use*
D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013974:Thyroxine