Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly.
BACKGROUND
Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH.


OBJECTIVE
To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly.


METHODS
Case series. Setting Institutional referral center at a tertiary care hospital. Patients Nineteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy.


METHODS
Before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels.


RESULTS
d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I.


CONCLUSIONS
The GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.
Bianchi
Antonio
A
Division of Endocrinology, School of Medicine, Catholic University, Largo A. Gemelli, 8, 00168, Rome, Italy, abianchi69@yahoo.it.
Mazziotti
Gherardo
G
Tilaro
Laura
L
Cimino
Vincenzo
V
Veltri
Flora
F
Gaetani
Eleonora
E
Pecorini
Giovanni
G
Pontecorvi
Alfredo
A
Giustina
Andrea
A
De Marinis
Laura
L
D000172:Acromegaly / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005091:Exons / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*; D055815:Young Adult
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant