[Pegvisomant--growth hormone receptor antagonist in the treatment of acromegaly].
BACKGROUND
Pegvisomant, growth hormone (GH) antagonist is a new perspective in the treatment of acromegaly. Pegvisomant interferes with GH action by competitive binding to receptor and blocking signal transduction. We present first experiences with treatment acromegaly with pegvisomant in Poland. Aim of the study was to assess pegvisomant efficacy in treatment patients with persistent acromegaly after transspheno-ideal surgery and unsatisfactory disease control with somatostatin analogue octreotide (OCTR).


METHODS
Material consisted of 10 patients (6 M, 4 F) aged 24-48 with active acromegaly, after neurosurgery, in which OCTR was ineffective in disease control. Patients with glucose metabolism disturbances were assigned to group receiving PEG. Controls were matched for age, sex, disease history, GH and IGF-1 levels. Patients received pegvisomant throughout 12 weeks, then combined therapy with PEG and OCTR-LAR was started for 8 weeks and then OCTR-LAR alone was given for next 8 weeks. Controls were medicated with OCTR-LAR 30 mg each 4 weeks during study. Clinical symptoms and IGF-1 level, fasting glucose and HbA(1c) was measured to assess treatment efficacy.


RESULTS
Pegvisomant reduced IGF-1 after first week of therapy from 1270+/-229 to 759+/-223 (40%, p<0.04). Prolonged therapy led to further IGF-1 decrease. After 12 weeks of treatment IGF-1 was significantly lower in comparison to initial as well as to controls (604 mg/l vs. 1270 and 1330, respectively, p<0.02). Combined therapy with PEG and OCTR-LAR was not superior to PEG alone. During treatment with pegvisomant improvement of glucose metabolism was seen, as well as decrease in insulin doses required. No adverse events was recorded.


CONCLUSIONS
Pegvisomant--GH receptor antagonist--effectively lowers IGF-1 concentration and improves disease control in patients with acromegaly after unsuccessful surgery and with octreotide unresponsiveness. Significantly improves glucose metabolism. Pegvisomant is indicated in patients with active acromegaly after standard treatment failure, especially in cases of coexistent diabetes mellitus.
Zgliczyński
Wojciech
W
Klinika Endokrynologii Centrum Medycznego Kształcenia Podyplomowego, Warszawa.
Zdunowski
Piotr
P
D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006727:Hormone Antagonists / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006727:Hormone Antagonists; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D015282:Octreotide; D011986:Receptors, Somatotropin; C517652:hemoglobin A1c protein, human; C406545:pegvisomant