Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance.
OBJECTIVE
The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and performance in patients with acromegaly.


METHODS
Seventeen patients (nine women, eight men, 27-61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, and hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/d, increasing by 5 mg/d every 6 wk on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/d.


RESULTS
After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular mass index (LVMi) was significantly decreased without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of left ventricle hypertrophy decreased from 50% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction as well as early to late (atrial) peak velocity ratio (E/A) were significantly increased, whereas isovolumic relaxation time was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular ejection fraction. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in one (8%) patient after 18 months of treatment.


CONCLUSIONS
Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.
Pivonello
Rosario
R
Department of Molecular and Clinical Endocrinology, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy. rpivone@tin.it
Galderisi
Maurizio
M
Auriemma
Renata S
RS
De Martino
Maria Cristina
MC
Galdiero
Mariano
M
Ciccarelli
Antonio
A
D'Errico
Arcangelo
A
Kourides
Ione
I
Burman
Pia
P
Lombardi
Gaetano
G
Colao
Annamaria
A
D000172:Acromegaly / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D003971:Diastole / Q000187:drug effects; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant