Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited.
OBJECTIVE
The prevalence of gsp mutations in GH-secreting pituitary adenomas was thought to differ geographically or racially, given its exceptionally lower incidence among Japanese patients (4.4-9.3%) compared to other regions (30-50%). However, this notion is now being challenged after a recent paper reported a 53.3% incidence among Japanese with acromegaly. We have since re-evaluated the prevalence of gsp mutations on a larger scale.


METHODS
One hundred Japanese acromegaly patients with surgically confirmed GH-secreting pituitary adenomas were enrolled.


METHODS
mRNAs from primary cultured adenomas were used for reverse transcriptase-polymerase chain reaction and direct sequencing of the Gsalpha subunit. Patient data were reviewed from medical charts.


RESULTS
There were 53 gsp mutations (53%), consisting of 42 Arg201Cys, one Arg201His, one Arg201Ser, 8 Gln227Leu, and one Gln227Arg mutation. Age at operation, sex ratio, basal serum GH and IGF-I levels were no different with or without the mutations. In contrast, patients responded differently to most dynamic tests with statistical significance: serum GH levels in gsp-positive patients had blunted response to GHRH, were well suppressed by bromocriptine, and had higher rates of paradoxical response to TRH. Notably, paradoxical response to LHRH was observed exclusively in gsp-negative patients. Octreotide suppressed GH levels strongly regardless of gsp status. These clinical characteristics are similar to those of Caucasian patients.


CONCLUSIONS
We conclude that the prevalence of gsp mutations in Japanese acromegaly patients is comparable to those of other reports from various regions. Therefore, Japanese patients do not stand as an example for geographical or racial difference in the prevalence of gsp mutations in GH-secreting pituitary adenomas.
Yasufuku-Takano
Junko
J
Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, Faculty of Medicine, Bunkyo-ku, Tokyo 113-8655, Japan.
Takano
Koji
K
Morita
Koji
K
Takakura
Kintomo
K
Teramoto
Akira
A
Fujita
Toshiro
T
D000172:Acromegaly / Q000208:ethnology / Q000378:metabolism; D000236:Adenoma / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D044466:Asian People; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007564:Japan; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D015995:Prevalence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D019205:GTP-Binding Protein alpha Subunits, Gs