Measurement of oxidative stress and endothelial dysfunction in patients with hypopituitarism and severe deficiency adult growth hormone deficiency.
Patients with adult GH deficiency (AGHD) have a high cardiovascular risk and probably an alteration of the oxidative balance, although evidence is lacking. To evaluate the presence of endothelial dysfunction and oxidative stress in patients with AGHD. Biochemical parameters of oxidative stress and endothelial dysfunction were compared in 25 patients with previously untreated AGHD and 25 healthy controls matched by age and sex. Multivariate analysis was performed to identify independent predictors of oxidative stress. Vascular function of subcutaneous resistance arteries was also analyzed by means of wire myography in 7 patients with untreated AGHD and in 7 healthy controls with similar characteristics. The values of C-reactive protein, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α), were higher in the AGHD group (4.6 vs. 0.2 μg/L, P = 0.02; 5.6 vs. 1.2 pg/mL, P = 0.001; 6.7 vs. 2.1 pg/mL, P = 0.04; respectively). The levels of type-1 vascular cell adhesion molecule, total anti-oxidant state, oxidized LDL (LDL-ox) were also greater in AGHD patients (678 vs. 423 ng/mL, P = 0.004; 1235.6 vs. 1002.3 μmol/L, P = 0.01; 172.2.5 vs. 42.3 ng/mL, P = 0.02; respectively). Nitric oxide (NO), reduced glutathione (GSH) and reduced/oxidized glutathione ratio (GSH/GSSG) values were lower than controls (18.7 vs. 31.6 mmol/mg protein, P = 0.01; 372.2 vs. 756.2 μmol/L, P = 0.03; 17.2 vs. 38.4, P = 0.04; respectively). Multiple regression analysis showed that AGHD was an independent predictor of increased LDL-ox (P = 0.002) and decreased GSH (P = 0.000). Furthermore, the degree of vascular relaxation to repeated exposure of acetylcholine was lower in AGHD (P = 0.025). Patients with AGHD have an increased degree of oxidative stress and endothelial dysfunction that could already be present in early stages of the disease. Studies with a greater number of patients are needed in order to confirm our findings.
Endocrinology Unit, Hospital Punta Europa de Algeciras, Carretera Getares, 11204 Algeciras, Cádiz, Spain. dgduarte@hipocampo.org
Daniel
D
González-Duarte
Ainara
A
Madrazo-Atutxa
Alfonso
A
Soto-Moreno
Alfonso
A
Leal-Cerro
D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000378:metabolism* / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D005609:Free Radicals; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D009569:Nitric Oxide; D002097:C-Reactive Protein; D005978:Glutathione; D019803:Glutathione Disulfide