Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.
OBJECTIVE
Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress.


METHODS
Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol).


RESULTS
LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively).


CONCLUSIONS
FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.
Shechter
M
M
The Heart Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel. shechtes@netvision.net.il
Ginsberg
S
S
Scheinowitz
M
M
Feinberg
M S
MS
Laron
Z
Z
D000328:Adult; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D025401:Echocardiography, Stress; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000172:deficiency*; D046150:Laron Syndrome / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D011986:Receptors, Somatotropin / Q000172:deficiency / Q000235:genetics; D012039:Regional Blood Flow; D014664:Vasodilation
D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone