Increase in serum pregnancy-associated plasma protein-A is correlated with increase in cardiovascular risk factors in adult patients with growth hormone deficiency
First Online: 29 May 2012 Received: 19 February 2012 Accepted: 03 May 2012 DOI:
10.1007/s12020-012-9697-9 Cite this article as: Li, L., Ren, W., Li, J. et al. Endocrine (2012) 42: 375. doi:10.1007/s12020-012-9697-9 Abstract
Adult Growth Hormone Deficiency (AGHD) is correlated to many adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues in recent study, and PAPP-A levels have been proposed as an early predictor of cardiac events. The aim of our study was to compare PAPP-A levels in AGHD patients with that of healthy adult subjects to determine if there is a relationship between serum PAPP-A and glucose and lipid metabolism. Twenty AGHD patients and 20 healthy, age-matched and weight-matched persons were chosen for the study. Their weight, height, blood pressure, body mass index (BMI), body fat percentage, waist and hip circumference, and waist–hips ratio were assessed. An oral glucose tolerance test was performed and venous blood was collected from the each patient’s cubital vein for biochemical analysis. Serum PAPP-A level in AGHD patients was significantly higher than that of the control group [(7.62 ± 1.62
vs. 6.54 ± 1.31) p < 0.05], and PAPP-A was positively correlated to age, BMI, waist circumference and so on. After adjusting for the waist circumference, waist–hip ratio, 2 h postprandial blood glucose, triglycerides, the serum PAPP-A in AGHD patients was positively correlated to the BMI ( r = 0.728, p < 0.05) and fasting insulin ( r = 0.433, p < 0.05). In a multiple step-wise regression analysis, BMI, 2 h postprandial glucose, fasting insulin, HOMA-IR were independently associated with serum PAPP-A in AGHD patients. The increase in serum PAPP-A levels is associated with abnormal glucose metabolism and increased risk of atherosclerosis in AGHD patients. Keyword Adult growth hormone deficiency Serum pregnancy-associated plasma protein-A Insulin tolerance test References
H.L. Fideleff, A. Chervin, A. Giaccio, P. Sobrado, R. Barmat et al., Adult growth hormone deficiency. Metabolic alterations and evaluation of different risk groups. Medicina (B Aires)
64, 13–19 (2004)
A. Sanmartí, A. Lucas, F. Hawkins, S.M. Webb, A. Ulied, Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (observational GH deficiency in adults) group. Eur. J. Endocrinol.
, 481–489 (1999)
B. Bülow, L. Hagmar, C.H. Nordström, Z. Mikoczy, E.M. Erfurth, Increased cerebrovascular mortality in patients with hypopituitarism. Clin. Endocrinol.
, 75–81 (1997)
J.W. Tomlinson, N. Holden, R.K. Hills, K. Wheatley, R.N. Clayton et al., Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet
, 425–431 (2001)
J. Svensson, B.-A. Bengtsson, T. Rosén, A. Odén, G. Johannsson et al., Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J. Clin. Endocrinol. Metab.
, 3306–3312 (2004)
M. Gola, S. Bonadonna, M. Doga, G. Mazziotti, A. Giustina, Cardiovascular risk in aging and obesity: is there a role for GH. J. Endocrinol. Invest.
, 759–767 (2005)
B. Bulow, L. Hangmar, J. Eskilsson, E.M. Erfurth, Hypopituitary females have a high incidence of cardiovascular morbidity and increased prevalence of cardiovascular risk factors. J. Clin. Endocrinol. Metab.
, 574–584 (2000)
A. Colao, C. Di Somma, S. Spiezia, S. Savastano, F. Rota et al., Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. J. Clin. Endocrinol. Metab.
, 3416–3424 (2008)
P.H. Su, S.F. Yang, J.S. Yu, S.J. Chen, J.Y. Chen, Study of the leptin levels and its gene polymorphisms in patients with idiopathic short stature and growth hormone deficiency. Endocrine (2012 in press)
A. Colao, C. Di Somma, M.C. Savanelli, M. De Leo, G. Lombardi, Beginning to end: cardiovascular implications of growth hormone (GH) deficiency and GH therapy. Growth Horm. IGF Res.
(Suppl A), S41–S48 (2006)
T. Mueller, B. Dieplinger, W. Poelz, M. Haltmayer, Increased pregnancy-associated plasma protein-A as a marker for peripheral atherosclerosis: results from the Linz Peripheral Arterial Disease Study. Clin. Chem.
, 1096–1103 (2006)
J.L. Beaudeux, L. Burc, F. Imbert-Bismut, P. Giral, M. Bernard et al., Serum/plasma pregnancy-associated protein A: a potential marker of echogenic carotid atherosclerotic plaques in a symptomatic hyperlipidemic subjects at high cardiovascular risk. Arterioscler. Thromb. Vasc. Biol.
, e7–e10 (2003)
C. Heeschen, S. Dimmeler, C.W. Hamm, S. Fichtlscherer, M.L. Simoons et al., Pregnancy associated plasma protein-A levels in patients with acute coronary syndromes:comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J. Am. Coll. Cardiol.
, 229–237 (2005)
M. Doga, S. Bonadonna, M. Gola, G. Mazziotti, A. Giustina, Growth hormone deficiency in the adult. Pituitary
, 305–311 (2006)
J.B. Lawrence, C. Oxvig, M.T. Overgaard, L. Sottrup-Jensen, G.J. Gleich et al., The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc. Natl. Acad. Sci. USA
, 3149–3153 (1999)
M.T. Overgaard, C. Oxvig, M. Christiansen, J.B. Lawrence, C.A. Conover et al., Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonproductive tissues. Biol. Reprod.
, 1083–1089 (1999)
G.A. Bayes, C.A. Conover, M.T. Overgaard, K.R. Bailey, M. Christiansen et al., Pregnancy-associated plasm a protein-A as a marker of acute coronary syndromes. N. Engl. J. Med.
, 1022–1029 (2001)
H.B. Boldt, M.T. Overgaard, L.S. Laursen, K. Weyer, L. Sottrup-Jensen et al., Mutational analysis of the proteolytic domain of pregnancy-associated plasma protein-A (PAPP-A): classification as a metzincin. Biochem J
, 267–359 (2001)
C. Joaquin, E. Aguilera, M.L. Granada, M.C. Pastor, I. Salinas et al., Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A. Eur. J. Endocrinol.
, 483–490 (2008)
D. González-Duarte, A. Madrazo-Atutxa, A. Soto-Moreno, A. Leal-Cerro, Measurement of oxidative stress and endothelial dysfunction in patients with hypopituitarism and severe deficiency adult growth hormone deficiency. Pituitary (2012 in press)
C.A. Conover, L.K. Bale, S.C. Harrington, Z.T. Resch, M.T. Overgaard, C. Oxvig, Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol. Am. J. Physiol. Cell Physiol.
, C183–C188 (2006)
A.L. Carrel, D.B. Allen, Effects of growth hormone on body composition and bone metabolism. Endocrine
, 163–172 (2000)
R. Sode-Carlsen, S. Farholt, K.F. Rabben, J. Bollerslev, T. Schreiner et al., Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study. Endocrine
, 191–199 (2012)
J.R. Sowers, Obesity as a cardiovascular risk factor. Am. J. Med.
, 37–41 (2003)
J.O. Johansson, J. Fowelin, K. Landin, I. Lager, B.A. Bengtsson, Growth hormone-deficient adults are insulin-resistant. Metabolism
, 1126–1129 (1995)
R. Arumugam, D. Fleenor, M. Freemark, Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors. Endocrine
, 182–191 (2007)
J. Ukropec, A. Penesová, M. Skopková, M. Pura, M. Vlcek et al., Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J. Clin. Endocrinol. Metab.
, 2255–2262 (2008)
N. Vahl, I. Klausen, J.S. Christiansen, J.O. Jørgensen, Growth hormone status is an independent determinant of serum levels of cholesterol and triglycerides in healthy subjects. Clin. Endocrinol.
, 309–316 (1999)
R. Abs, U. Feldt-Rasmussen, A.F. Mattsson, J.P. Monson, B.A. Bengtsson et al., Determinants of cardiovascular risk in 2,589 hypopituitary growth hormone-deficient adults. Eur. J. Endocrinol.
, 79–90 (2006)
Y. Momiyama, R. Ohmori, Z.A. Fayad, T. Kihara, N. Tanaka et al., Association between plasma C-reactive protein levels and the severities of coronary and aortic atherosclerosis. J. Atheroscler. Thromb.
, 460–467 (2010)
A. Juul, T. Scheike, M. Davidsen, J. Gyllenborg, T. Jørgensen, Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation
, 939–944 (2002)
K.K. Miller, T. Wexler, P. Fazeli, L. Gunnell, G.J. Graham et al., Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement. J. Clin. Endocrinol. Metab.
, 567–577 (2010)
C. Beauregard, A.L. Utz, A.E. Schaub, L. Nachtigall, B.M. Biller et al., Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab.
, 2063–2071 (2008)
K.A. Al-Shoumer, K. Ali, V. Anyaoku, R. Niththyananthan, D.G. Johnston, Overnight metabolic fuel deficiency in patients treated conventionally for hypopituitarism. Clin. Endocrinol. (Oxf)
, 171–178 (1996)
Y. Kato, H.Y. Hu, M. Sohmiya, Short-term treatment with different doses of human growth hormone in adult patients with growth hormone deficiency. Endocr. J.
, 177–183 (1996)
E. Kousta, A. Chrisoulidou, N.J. Lawrence, V. Anyaoku, K.A. Al-Shoumer et al., The effects of growth hormone replacement therapy on over night metabolic fuels in hypopituitary patients. Clin. Endocrinol. (Oxf)
, 17–24 (2000)
CrossRef Copyright information
© Springer Science+Business Media, LLC 2012