Journal of Endocrinological Investigation

, Volume 26, Issue 10, pp 1001–1007 | Cite as

Determination of oxidative protein and lipid damage in adult hypopituitary patients with GH deficiency

  • N. Özbey
  • A. Telci
  • U. Cakatay
  • A. Yurci
  • S. Molvalilar
Original Article


The aim of this study is to determine oxidative protein and lipid damage in adult hypopituitary GH-deficient patients. Eighteen hypopituitary GH-deficient — otherwise healthy — adults on conventional replacement therapy other than GH (9 male, 9 female, age 41.8±16.4 yr) and 18 healthy subjects (6 male, 12 female, age 40.3±16.2 yr) participated in the study. Plasma products of oxidative protein damage [protein carbonyl (PCO) and nitrotyrozine (NT)], plasma oxidized LDL (oxLDL), plasma product of oxidative lipid damage [lipid hydroperoxide (LHP)] and antioxidant status of the plasma [total thiol (T-SH)] were measured. Body fat percentage, total and LDL-cholesterol concentrations were significantly higher in the hypopituitary group. Plasma PCO, NT, LHP and T-SH concentrations did not differ significantly between patients and controls. OxLDL concentration was significantly higher in the hypopituitary patients (62.4±17.8 vs 43.1±11.3 U/l, p=0.001). In the patients, oxLDL correlated significantly with the duration of hypopituitarism (r=0.6323, p=0.01). In the controls, oxLDL correlated significantly with blood pressure, total and VLDL-cholesterol concentrations. Increased oxLDL concentration may indicate increased oxidative stress within the vascular compartment and may contribute to the proatherogenic state in GH-deficient hypopituitary patients independent from conventional risk factors.


Oxidative stress hypopituitarism premature atherosclerosis oxidized LDL oxidative protein damage 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990, 336: 285–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Bates AS, Hoff WV, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996, 81: 1169–72.PubMedGoogle Scholar
  3. 3.
    Bülow B, Hagmar L, Mikoczy Z, Nordström C-H, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 1997, 46: 75–81.CrossRefGoogle Scholar
  4. 4.
    Tomlinson JW, Holden N, Hills RK, et al. and the West Midlands Prospective Hypopituitary Study Group 2001. Association between premature mortality and hypopituitarism. Lancet 2001, 357: 425–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Stavrou S, Kleinberg DL. Diagnosis and management of GH deficiency in adults. Endocrinol Metab Clin North Am 2001, 30: 545–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Markussis V, Besyah SA, Fischer C, Sharp P, Nicolaides AN, Johnston DG. Detection of premature atherosclerosis by high resolution ultrasonography in symptom free hypopituitary adults. Lancet 1992, 340: 1188–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Capaldo B, Patti L, Pliviero U, et al. Increased arterial intima media thickness in childhood onset growth hormone deficiency. J Clin Endocrinol Metab 1997, 82: 1373–81.Google Scholar
  8. 8.
    Markussis V, Beshyah SA, Fischer C, Parker K, Nicolaides AN, Johnston DG. Abnormal carotid artery wall dynamics in symptom free hypopituitary adults. Eur J Endocrinol 1997, 136: 157–64.PubMedCrossRefGoogle Scholar
  9. 9.
    Evans LM, Davies JS, Anderson RA, et al. The effect of GH replacement therapy on endothelial function and oxida-tive stress in adult growth hormone deficiency. Eur J Endocrinol 2000, 142: 254–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Sesmilo G, Miller KK, Hayden D, Klibanski A. Inflammatory cardiovascular risk markers in women with hypopituitarism. J Clin Endocrinol Metab 2001, 86: 5774–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Carroll PV, Christ ER, Bengtsson BA, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998, 83: 382–95.PubMedCrossRefGoogle Scholar
  12. 12.
    Besyah SA, Johnston DG. Cardiovascular disease risk and risk factors in adults with hypopituitarism. Clin Endocrinol (Oxf) 1999, 50: 1–15.CrossRefGoogle Scholar
  13. 13.
    Rosen T, Eden S, Larson G, Wilhelmsen L, Bengtsson BA. Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 1993, 129: 125–200.Google Scholar
  14. 14.
    Stadtman ER, Levine RL. Protein oxidation. Ann NY Acad Sci 2000, 899: 191–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Hazell LJ, Baernthale G, Stocker R. Correlation between intima-to-media ratio, apoprotein B-100, myeloperoxidase and hypochlorite-oxidized proteins in human atherosclerosis. Free Radic Biol Med 2000, 31: 1254–62.CrossRefGoogle Scholar
  16. 16.
    Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 1997, 324: 1–18.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Signorelli SS, Neri S, Di Pino L, et al. Oxidative stress and endothelial damage in patients with asymptomatic carotid atherosclerosis. Clin Exp Med 2001, 1: 9–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994, 233: 357–63.PubMedCrossRefGoogle Scholar
  19. 19.
    Shanlin FU, Davies MJ, Stocker R, Dean RT. Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque. Biochem J 1998, 333: 519–25.Google Scholar
  20. 20.
    Dominguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care 21: 1736–42, 1998.PubMedCrossRefGoogle Scholar
  21. 21.
    Telci A, Çakatay U, Kayah R, et al. Oxidative protein damage in plasma of type 2 diabetic patients. Horm Metab Res 2000, 32: 40–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Hu ML. Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 1994, 233: 381–5.Google Scholar
  23. 23.
    Bourdon E, Loreau D, Blache D. Glucose and free radicals impair the antioxidant properties of serum albumin. FASEB J 1999, 13: 233–44.PubMedGoogle Scholar
  24. 24.
    Ischiropoulos H, Al-Mehdi AB. Peroxynitrite-mediated oxidative protein modification. FEBS Lett 1995, 364: 279–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Gow AJ, Duran D, Malcolm S, Ischiropoulos H. Effects of per-oxynitrite-induced protein modifications on tyrosine phosphorylation and degradation. FEBS Lett 1996, 385: 63–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Ter Steege JCA, Koster-Kamphuis L, Van Straaten EA, Forget PP, Buurman WA. Nitrotyrosine in plasma of celiac disease patients as detected by a new sandwich ELISA. Free Radic Biol Med 1998, 25: 953–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Salman-Tabcheh S, Guerin MC, Tirreilles J. Nitration of tyrosyl-residues from extra- and intracellular proteins in human whole blood. Free Radic Biol Med 1995, 19: 695–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Ross R. Atherosclerosis — an inflammatory disease. N Engl J Med 1999, 340: 115–26.PubMedCrossRefGoogle Scholar
  29. 29.
    Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 1998, 98: 1487–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Holvoet P, Stassen J-M, Van Cleemput J, Collen D, Vanhaecke J. Oxidized low density lipoprotein in patients with transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 1998, 18: 100–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Holvoet P, Van Cleemput J, Collen D, Vanhaecke J. Oxidized low density lipoprotein is a prognostic marker of transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 2000, 20: 698–702.PubMedCrossRefGoogle Scholar
  32. 32.
    Holvoet P, Mertens A, Verhamme P, et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001, 21: 844–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Nourooz-Zadeh J, Tajaddini-Sarmadi J, McCarthy S, Betteridge DJ, Wolff SP. Elevated levels of authentic plasma hydroperoxides in NIDDM. Diabetes 1995, 44: 1054–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Hartman ML, Crowe BJ, Biller BMK, Ho KKY, Clemmons DR, Chipman JJ. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 2002, 87: 477–85.PubMedCrossRefGoogle Scholar
  35. 35.
    Gomez JM, Espadero RM, Escobar-Jimenez F, et al. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 2002, 56: 329–34.CrossRefGoogle Scholar
  36. 36.
    Nourooz-Zadeh J. Ferrous ion oxidation in presence of xylenol orange for detection of lipid hydroperoxides in plasma. Methods Enzymol 1999, 300: 58–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Smith JC, Lang D, McEneny J, et al. Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency. Clin Endocrinol (Oxf) 2002, 56: 449–55.CrossRefGoogle Scholar
  38. 38.
    Smith JC, Evans LM, Wilkinson I, et al. Effects of GH replacement on endothelial function and large artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf) 2002, 56: 493–501.CrossRefGoogle Scholar
  39. 39.
    Ozbey N, Aydin A, Telci A, Cakatay U. Antibodies against oxidised low density lipoprotein in hypopituitary patients with growth hormone deficiency. Endocr J 2001, 48: 579–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Pfeifer M, Verhovec R, Zizec B, Prezelj J, Poredos P, Clayton RN. Growth hormone treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999, 84: 453–7.PubMedGoogle Scholar
  41. 41.
    Munzel T, Heitzer T, Harrison DG. The physiology and pathophysiology of the nitricoxide/superoxide system. Herz 1997, 22: 58–172.CrossRefGoogle Scholar
  42. 42.
    Böger RH, Skamira C, Bode-Böger SM, et al. Nitric oxide may mediate the haemodynamic effects of recombinant human growth hormone in patients with acquired growth hormone deficiency. J Clin Invest 1996, 98: 2706–13.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Tsukahara H, Gordienko DV, Tonshoff B, Gelato MC, Goligorsky MS. Direct demonstration of insulin-like growth factor 1 induced nitric oxide production by endothelial cells. Kidney Int 1994, 45: 598–604.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2003

Authors and Affiliations

  • N. Özbey
    • 1
  • A. Telci
    • 2
  • U. Cakatay
    • 2
  • A. Yurci
    • 1
  • S. Molvalilar
    • 1
  1. 1.Department of Internal Medicine, Division of EndocrinologyIstanbul UniversityMerter/IstanbulTurkey
  2. 2.Central Laboratory of Clinical Biochemistry, Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations