Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency

OBJECTIVE To investigate the role of IGF-1 on intima-media thickness (IMT) at common carotid arteries by Doppler ultrasonography. SUBJECTS Thirty-nine patients (17 women, 22 men, aged 25-70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF-1 levels, and 39 sex-, age- and body mass index (BMI)-matched healthy controls. RESULTS Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0.88 +/- 0.26 vs. 0.69 +/- 0.14 mm, P < 0.001), and systolic and diastolic peak velocity (P < 0.001) compared to controls. Eight patients (18%) and one control (2.1%, P = 0.04) had well-defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0.78, P < 0.001). In both controls (r = -0.82; P < 0.0001) and patients with GHD (r = -0.84, P < 0.0001), serum IGF-1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH-deficient patients were total cholesterol levels (t = 5.2, P < 0.001), followed by disease duration (t = 2.4, P = 0.02), while in controls the variables most significantly related to IMT were IGF-1 levels (t = -9.9, P < 0.001), followed by low density lipoprotein (LDL)-cholesterol levels (t = -2.3, P = 0.02). Compared to patients with normal IGF-1 levels, those with low IGF-1 levels had lower high density lipoprotein (HDL)-cholesterol levels (1.0 +/- 0.2 vs. 1.3 +/- 0.2 mmol/l, P = 0.0002), and higher glucose (54.3 +/- 6.1 vs. 48.9 +/- 5.9 mmol/l, P = 0.008), insulin (25.2 +/- 6.8 vs. 18.8 +/- 6.0 mUl/l, P = 0.004), total cholesterol (7.1 +/- 1.1 vs. 4.9 +/- 0.6 mmol/l, P < 0.0001), total/HDL-cholesterol ratio (7.2 +/- 1.8 vs. 3.9 +/- 0.7, P < 0.0001), fibrinogen levels (319.8 +/- 56.9 vs. 241.8 +/- 53.0 mg/dl, P < 0.0001) and mean IMT at common carotid arteries (1.05 +/- 0.25 vs. 0.69 +/- 0.07 mm, P < 0.0001). Atherosclerotic plaques were found only in GH-deficient patients with low IGF-1 levels. CONCLUSIONS GH-deficient patients have alterations in lipid profile with an increase in the total/HDL-cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF-1 deficiency have increased IMT.