The treatment with growth hormone receptor antagonist in acromegaly: effect on vascular structure and function in patients resistant to somatostatin analogues.
BACKGROUND
Acromegaly is known to be associated to vascular damage characterized by an increase of vascular wall thickness and an impairment of vascular function.


OBJECTIVE
The aim of this study was to evaluate the effect of medical treatment with the GH receptor antagonist pegvisomant on vascular structure and function in acromegalic patients resistant to somatostatin analogues.


METHODS
Ten patients (4 males and 6 females, 28-58 yr) and 20 sex-, age-, and body mass index-matched healthy controls entered the study. All patients were treated for 18 months with pegvisomant at doses ranging from 10 to 40 mg/day.


METHODS
Primary outcome measures were measurement of carotid arteries intima-media thickness (IMT), and brachial arteries flow mediated dilation (FMD); secondary outcome measures were blood pressure, blood glucose and lipids levels.


RESULTS
Carotid arteries maximal IMT was significantly higher in patients than in controls at baseline (1.18±0.59 vs 0.69±0.13, p=0.001) and slightly, but not significantly, decreased after treatment (0.97±0.17). Brachial arteries FMD was significantly lower in patients than controls at baseline (7.5±2.5 vs 13.1±1.4, p<0.001) and significantly increased after treatment (8.8±3.7, p=0.016). Systolic (SBP) and diastolic (DBP) blood pressure values, serum glucose and insulin levels and homeostasis model assessment (HOMA) index were higher, whereas HDL-cholesterol levels were lower in patients than controls at baseline. After treatment, SBP and DBP, as well as serum glucose and insulin levels and HOMA index significantly decreased whereas no significant change was found in serum lipid profile.


CONCLUSIONS
The results of the current study suggested that long-term treatment with pegvisomant induced a slight reduction of carotid arteries wall thickness and a significant improvement of brachial arteries vascular function in patients with acromegaly resistant to somatostatin analogues.
De Martino
M C
MC
Departments of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, via S. Pansini 5, Naples, Italy.
Auriemma
R S
RS
Brevetti
G
G
Vitale
G
G
Schiano
V
V
Galdiero
M
M
Grasso
L
L
Lombardi
G
G
Colao
A
A
Pivonello
R
R
D000172:Acromegaly / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000328:Adult; D001808:Blood Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D001916:Brachial Artery / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D002318:Cardiovascular Diseases / Q000209:etiology; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D013004:Somatostatin / Q000031:analogs & derivatives*; D014463:Ultrasonography
D006727:Hormone Antagonists; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; C406545:pegvisomant