N-terminal pro-B-type natriuretic peptide in patients with growth hormone disturbances
Mikkel Andreassen,
Jens Faber,
Henrik Vestergaard,
Caroline Kistorp,
Lars Østergaard Kristensen,
Mikkel Andreassen
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorJens Faber
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorHenrik Vestergaard
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorCaroline Kistorp
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorLars Østergaard Kristensen
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorMikkel Andreassen,
Jens Faber,
Henrik Vestergaard,
Caroline Kistorp,
Lars Østergaard Kristensen,
Mikkel Andreassen
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorJens Faber
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorHenrik Vestergaard
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorCaroline Kistorp
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this authorLars Østergaard Kristensen
Department of Endocrinology and Internal Medicine J106, Copenhagen University Hospital Herlev, Denmark
Search for more papers by this author Mikkel Andreassen, Endocrine Laboratory 54o4, KAS Herlev, Herlev ringvej 75, 2730 Herlev, Denmark. Tel.: + 45 44883420; Fax: + 4544884838; E-mail: [email protected]
Summary
Background Acromegaly is associated with hypertrophic cardiomyopathy, hypertension and subsequent congestive heart failure. Impairment of cardiac function has also been associated with growth hormone deficiency (GHD). B-type natriuretic peptides (BNPs) have emerged as strong diagnostic and prognostic risk markers. They are cardioprotective hormones that compensate heart disease by promoting natriuresis and modulation of cardiac hypertrophy in response to volume expansion and ventricular wall stretch.
Objective To investigate N-terminal pro-BNP (NT-proBNP) in patients with GH disturbances before and after treatment, and in healthy gender- and age-matched controls.
Subjects and methods Ten acromegalic patients (age 48 ± 12 years) and 10 patients with GHD (age 41 ± 14 years) were studied. None had symptoms or signs of cardiovascular disease except for hypertension. Serum NT-proBNP was measured before and 3, 6, 12 and 24 months after treatment.
Results Baseline NT-proBNP was lower in acromegalic patients [median (interquartile range) 24·3 (17·8–33·0) pg/ml] than in 20 healthy matched controls [57·9 (35·4–92·2) pg/ml; P < 0·001]. NT-proBNP increased during treatment (P = 0·002), concomitant with a decrease in IGF-I (P < 0·001). After 3 months of treatment NT-proBNP peaked, with a fourfold increase to 96·4 (57·8–113·2) pg/ml. NT-proBNP did not differ in patients with GHD compared with controls (P = 0·19), and did not change during treatment (P = 0·39).
Conclusion Untreated patients with acromegaly had low NT-proBNP levels that increased fourfold after treatment. This is in contrast to other conditions with cardiac hypertrophy. Further studies are required to determine the significance of this novel finding in relation to acromegalic cardiac disease.
References
- 1 Frystyk, J., Ledet, T., Moller, N., Flyvbjerg, A. & Orskov, H. (2002) Cardiovascular disease and insulin-like growth factor I. Circulation, 106, 893–895.
- 2 Colao, A., Marzullo, P., Di, S.C. & Lombardi, G. (2001) Growth hormone and the heart. Clinical Endocrinology, 54, 137–154.
- 3 Moller, J. (2003) Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects. Growth Hormone and IGF Research, 13, 55–74.
- 4
Clayton, R.N. (2003) Cardiovascular function in acromegaly.
Endocrine Review, 24, 272–277.
10.1210/er.2003-0009 Google Scholar
- 5 Rajasoorya, C., Holdaway, I.M., Wrightson, P., Scott, D.J. & Ibbertson, H.K. (1994) Determinants of clinical outcome and survival in acromegaly. Clinical Endocrinology, 41, 95–102.
- 6 Lopez-Velasco, R., Escobar-Morreale, H.F., Vega, B., Villa, E., Sancho, J.M., Moya-Mur, J.L. & Garcia-Robles, R. (1997) Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension? Journal of Clinical Endocrinology and Metabolism, 82, 1047–1053.
- 7 Swearingen, B., Barker, F.G., Katznelson, L., Biller, B.M., Grinspoon, S., Klibanski, A., Moayeri, N., Black, P.M. & Zervas, N.T. (1998) Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. Journal of Clinical Endocrinology and Metabolism, 83, 3419–3426.
- 8 Kauppinen-Makelin, R., Sane, T., Reunanen, A., Valimaki, M.J., Niskanen, L., Markkanen, H., Loyttyniemi, E., Ebeling, T., Jaatinen, P., Laine, H., Nuutila, P., Salmela, P., Salmi, J., Stenman, U.H., Viikari, J. & Voutilainen, E. (2005) A nationwide survey of mortality in acromegaly. Journal of Clinical Endocrinology and Metabolism, 90, 4081–4086.
- 9 Rosen, T. & Bengtsson, B.A. (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet, 336, 285–288.
- 10 Bates, A.S., Van't Hoff, W., Jones, P.J. & Clayton, R.N. (1996) The effect of hypopituitarism on life expectancy. Journal of Clinical Endocrinology and Metabolism, 81, 1169–1172.
- 11 Tomlinson, J.W., Holden, N., Hills, R.K., Wheatley, K., Clayton, R.N., Bates, A.S., Sheppard, M.C. & Stewart, P.M. (2001) Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet, 357, 425–431.
- 12 Svensson, J., Tivesten, A. & Isgaard, J. (2005) Growth hormone and the cardiovascular function. Minerva Endocrinology, 30, 1–13.
- 13 Svensson, J., Bengtsson, B.A., Rosen, T., Oden, A. & Johannsson, G. (2004) Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. Journal of Clinical Endocrinology and Metabolism, 89, 3306–3312.
- 14 Barkan, A.L., Clemmons, D.R., Molitch, M.E., Stewart, P.M. & Young, W.F. Jr (2000) Growth hormone therapy for hypopituitary adults: time for re-appraisal. Trends in Endocrinology and Metabolism, 11, 238–245.
- 15 Colao, A., Di Somma, C., Cuocolo, A., Spinelli, L., Acampa, W., Spiezia, S., Rota, F., Savanelli, M.C. & Lombardi, G. (2005) Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency. Journal of Clinical Endocrinology and Metabolism, 90, 5146–5155.
- 16 Valcavi, R., Gaddi, O., Zini, M., Iavicoli, M., Mellino, U. & Portioli, I. (1995) Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. Journal of Clinical Endocrinology and Metabolism, 80, 659–666.
- 17 Maison, P. & Chanson, P. (2003) Cardiac effects of growth hormone in adults with growth hormone deficiency: a meta-analysis. Circulation, 108, 2648–2652.
- 18 Sneppen, S.B., Steensgaard-Hansen, F. & Feldt-Rasmussen, U. (2002) Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, double-blind study. Hormone Research, 58, 21–29.
- 19 Climent, V.E., Pico, A., Sogorb, F., Aznar, S., Lip, G.Y. & Marin, F. (2006) Growth hormone therapy and the heart. American Journal of Cardiology, 97, 1097–1102.
- 20 Munagala, V.K., Burnett, J.C. Jr & Redfield, M.M. (2004) The natriuretic peptides in cardiovascular medicine. Current Problems in Cardiology, 29, 707–769.
- 21 Lukowicz, T.V., Fischer, M., Hense, H.W., Doring, A., Stritzke, J., Riegger, G., Schunkert, H. & Luchner, A. (2005) BNP as a marker of diastolic dysfunction in the general population: importance of left ventricular hypertrophy. European Journal of Heart Failure, 7, 525–531.
- 22 Tschope, C., Kasner, M., Westermann, D., Gaub, R., Poller, W.C. & Schultheiss, H.P. (2005) The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction: correlation with echocardiographic and invasive measurements. European Heart Journal, 26, 2277–2284.
- 23 Rivera Otero, J.M., Talens-Visconti, R., Salvador, A., Bertomeu, V., Miro, V., Jordan, A., Sogorb, F., Cortes, R., Paya, R., Diago, J.L. & Grau, G. (2004) Ventricular hypertrophy increases NT-proBNP in subjects with and without hypertension. International Journal of Cardiology, 96, 265–271.
- 24 Nishikimi, T., Maeda, N. & Matsuoka, H. (2006) The role of natriuretic peptides in cardioprotection. Cardiovascular Research, 69, 318–328.
- 25 Mueller, T., Gegenhuber, A., Dieplinger, B., Poelz, W. & Haltmayer, M. (2004) Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples. Clinical Chemistry and Laboratory Medicine, 42, 942–944.
- 26 Schou, M., Gustafsson, F., Nielsen, P.H., Madsen, L.H., Kjaer, A. & Hildebrandt, P.R. (2007) Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state. European Journal of Heart Failure, 9, 68–74.
- 27 Kistorp, C., Raymond, I., Pedersen, F., Gustafsson, F., Faber, J. & Hildebrandt, P. (2005) N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. Journal of the American Medical Association, 293, 1609–1616.
- 28 Swedberg, K., Clealand, J., Dargie, H., Drexler, H., Follath, F., Komajda, M., Tavazzi, L. & Smiseth, O. (2005) Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). European Heart Journal 26, 1115–1140.
- 29 Andersen, M., Hansen, T.B., Støving, R.K., Bertelsen, J., Hangaard, J., Hyltoft Petersen, P. & Hagen, C. (1996) The pyridostigmine–growth-hormone-releasing-hormone in adults. The reference interval and a comparison with the insulin tolerance test. Endocrinology and Metabolism, 3, 197–206.
- 30 Landin-Wilhelmsen, K., Wilhelmsen, L., Lappas, G., Rosen, T., Lindstedt, G., Lundberg, P.A. & Bengtsson, B.A. (1994) Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clinical Endocrinology, 41, 351–357.
- 31 Manjunath, G., Sarnak, M.J. & Levey, A.S. (2001) Prediction equations to estimate glomerular filtration rate: an update. Current Opinion in Nephrology and Hypertension, 10, 785–792.
- 32 Harder, B.A., Schaub, M.C., Eppenberger, H.M. & Eppenberger-Eberhardt, M. (1996) Influence of fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-I) on cytoskeletal and contractile structures and on atrial natriuretic factor (ANF) expression in adult rat ventricular cardiomyocytes in culture. Journal of Molecular and Cellular Cardiology, 28, 19–31.
- 33 Hall, C. (2005) NT-ProBNP: the mechanism behind the marker. Journal of Cardiac Failure, 11, S81–S83.
- 34 O'Shea, M.H. & Layish, D.T. (1992) Growth hormone and the kidney: a case presentation and review of the literature. Journal of the American Society of Nephrology, 3, 157–161.
- 35 Olsen, M.H., Hansen, T.W., Christensen, M.K., Gustafsson, F., Rasmussen, S., Wachtell, K., Borch-Johnsen, K., Ibsen, H., Jorgensen, T. & Hildebrandt, P. (2005) N-terminal pro-brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension, 46, 660–666.
- 36 Kaji, H., Sugimoto, T., Nakaoka, D., Okimura, Y., Kaji, H., Abe, H. & Chihara, K. (2001) Bone metabolism and body composition in Japanese patients with active acromegaly. Clinical Endocrinology, 55, 175–181.
- 37 Bengtsson, B.A., Brummer, R.J. & Bosaeus, I. (1990) Growth hormone and body composition. Hormone Research, 33 (Suppl. 4), 19–24.
- 38 Das, S.R., Drazner, M.H., Dries, D.L., Vega, G.L., Stanek, H.G., Abdullah, S.M., Canham, R.M., Chung, A.K., Leonard, D., Wians, F.H. Jr & De Lemos, J.A. (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation, 112, 2163–2168.
- 39 Oliver, P.M., Fox, J.E., Kim, R., Rockman, H.A., Kim, H.S., Reddick, R.L., Pandey, K.N., Milgram, S.L., Smithies, O. & Maeda, N. (1997) Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proceedings of the National Academy of Science of the United States of America, 94, 14730–14735.
- 40 Schultz, M., Faber, J., Kistorp, C., Jarlov, A., Pedersen, F., Wiinberg, N. & Hildebrandt, P. (2004) N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) in different thyroid function states. Clinical Endocrinology, 60, 54–59.
- 41 Wang, T.J., Larson, M.G., Levy, D., Benjamin, E.J., Leip, E.P., Wilson, P.W. & Vasan, R.S. (2004) Impact of obesity on plasma natriuretic peptide levels. Circulation, 109, 594–600.
- 42 Soszynski, P., Slowinska-Srzednicka, J. & Zgliczynski, S. (1991) Plasma concentrations of atrial natriuretic hormone in acromegaly: relationship to hypertension. Acta Endocrinologica (Copenhagen), 125, 268–272.
- 43 Deray, G., Chanson, P., Maistre, G., Warnet, A., Eurin, J., Barthelemy, C., Masson, F., Martinez, F., Lubetzki, J. & Legrand, J.C. (1990) Atrial natriuretic factor in patients with acromegaly. European Journal of Clinical Pharmacology, 38, 409–413.
- 44 Moller, J., Jorgensen, J.O., Moller, N., Hansen, K.W., Pedersen, E.B. & Christiansen, J.S. (1991) Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man. Journal of Clinical Endocrinology and Metabolism, 72, 768–772.
- 45 McKnight, J.A., McCance, D.R., Hadden, D.R., Kennedy, L., Roberts, G., Sheridan, B. & Atkinson, A.B. (1989) Basal and saline-stimulated levels of plasma atrial natriuretic factor in acromegaly. Clinical Endocrinology, 31, 431–438.
- 46 Ekman, B., Ohman, P.K., Arnqvist, H.J., Lindstrom, T. & Nystrom, F.H. (2002) Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system. Clinical Endocrinology, 57, 473–479.
- 47 Johannsson, G., Sverrisdottir, Y.B., Ellegard, L., Lundberg, P.A. & Herlitz, H. (2002) GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis. Journal of Clinical Endocrinology and Metabolism, 87, 1743–1749.
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