Advertisement

Pituitary

, Volume 15, Issue 1, pp 50–58 | Cite as

Improvement of cardiac parameters in patients with acromegaly treated with medical therapies

  • Annamaria ColaoEmail author
Article

Abstract

In acromegaly, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess results in a specific cardiomyopathy characterized by concentric cardiac hypertrophy primarily associated with diastolic dysfunction that can lead to impaired systolic function and eventually heart failure. This review of the literature evaluates the effect of therapeutic intervention on cardiac parameters. Clinical studies investigating the impact of treatments for acromegaly on cardiac function published between January 1980 and January 2009 were identified through electronic searches of Medline. Suppression of GH and IGF-1 following surgery or medical treatment with somatostatin analogue therapy is effective in decreasing left ventricular (LV) hypertrophy, with subsequent improvement in cardiac function. First-line treatment with somatostatin analogues resulted in improved cardiac outcome compared with first-line surgery, possibly due to somatostatin analogues acting directly through somatostatin receptors on cardiac cells. Additional cardiac improvement has been reported when somatostatin analogue treatment was combined with surgery. In patients where complete biochemical control was not achieved, an improved cardiac performance following treatment with somatostatin analogues has been reported. Treatment with pegvisomant has been demonstrated to reduce LV hypertrophy and improve diastolic and systolic performance. In contrast, reports have suggested that treatment with the dopamine agonist cabergoline increased the incidence of valvular heart disease. Although surgery and somatostatin analogues are effective in improving cardiomyopathy, a greater beneficial effect is observed with somatostatin analogue treatment. Selected patients with acromegaly should consider first-line therapy or pre-treatment with somatostatin analogues prior to surgery to achieve biochemical control and improve cardiac dysfunction.

Keywords

Acromegaly Somatostatin analogues Pegvisomant Cardiomyopathy Cardiac function 

Notes

Acknowledgments

The author thanks Claire Routley, PhD, for medical editorial assistance with this manuscript. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Conflicts of interest

The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical standards

The author declares that the experiments comply with the Italian current laws.

References

  1. 1.
    Melmed S (2006) Medical progress: acromegaly. N Engl J Med 355:2558–2573PubMedCrossRefGoogle Scholar
  2. 2.
    Holdaway IM, Rajasoorya C (1999) Epidemiology of acromegaly. Pituitary 2:29–41PubMedCrossRefGoogle Scholar
  3. 3.
    Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:4769–4775PubMedCrossRefGoogle Scholar
  4. 4.
    Schneider HJ, Sievers C, Saller B, Wittchen HU, Stalla GK (2008) High prevalence of biochemical acromegaly in primary care patients with elevated IGF-1 levels. Clin Endocrinol (Oxf) 69:432–435CrossRefGoogle Scholar
  5. 5.
    Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25:102–152PubMedCrossRefGoogle Scholar
  6. 6.
    Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89:667–674PubMedCrossRefGoogle Scholar
  7. 7.
    Colao A, Marzullo P, di Somma C, Lombardi G (2001) Growth hormone and the heart. Clin Endocrinol (Oxf) 54:137–154CrossRefGoogle Scholar
  8. 8.
    Gilbert PL, Siegel RJ, Melmed S, Sherman CT, Fishbein MC (1985) Cardiac morphology in rats with growth hormone-producing tumours. J Mol Cell Cardiol 17:805–811PubMedCrossRefGoogle Scholar
  9. 9.
    Ito H, Hiroe M, Hirata Y, Tsujino M, Adachi S, Shichiri M, Koike A, Nogami A, Marumo F (1993) Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 87:1715–1721PubMedGoogle Scholar
  10. 10.
    Chen DB, Wang L, Wang PH (2000) Insulin-like growth factor I retards apoptotic signaling induced by ethanol in cardiomyocytes. Life Sci 67:1683–1693PubMedCrossRefGoogle Scholar
  11. 11.
    Stromer H, Cittadini A, Douglas PS, Morgan JP (1996) Exogenously administered growth hormone and insulin-like growth factor-I alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart. Circ Res 79:227–236PubMedGoogle Scholar
  12. 12.
    Lie JT (1980) Pathology of the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J 100:41–52PubMedCrossRefGoogle Scholar
  13. 13.
    van der Klaauw AA, Bax JJ, Bleeker GB, Holman ER, Delgado V, Smit JW, Romijn JA, Pereira AM (2008) Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls. Eur J Endocrinol 159:705–712PubMedCrossRefGoogle Scholar
  14. 14.
    Bogazzi F, Lombardi M, Strata E, Aquaro G, Di Bello V, Cosci C, Sardella C, Talini E, Martino E (2008) High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging. Clin Endocrinol (Oxf) 68:361–368Google Scholar
  15. 15.
    Di Bello V, Bogazzi F, Di Cori A, Palagi C, Delle Donne MG, Gavioli S, Talini E, Cosci C, Sardella C, Tonti G, Martino E, Balbarini A, Mariani M (2006) Myocardial systolic strain abnormalities in patients with acromegaly: a prospective color Doppler imaging study. J Endocrinol Invest 29:544–550PubMedGoogle Scholar
  16. 16.
    Pereira AM, Van Thiel SW, Lindner JR, Roelfsema F, van der Wall EE, Morreau H, Smit JW, Romijn JA, Bax JJ (2004) Increased prevalence of regurgitant valvular heart disease in acromegaly. J Clin Endocrinol Metab 89:71–75PubMedCrossRefGoogle Scholar
  17. 17.
    Maffei P, Martini C, Milanesi A, Corfini A, Mioni R, De Carlo E, Menegazzo C, Scanarini M, Vettor R, Federspil G, Sicolo N (2005) Late potentials and ventricular arrhythmias in acromegaly. Int J Cardiol 104:197–203PubMedCrossRefGoogle Scholar
  18. 18.
    Fatti LM, Scacchi M, Lavezzi E, Giraldi FP, De Martin M, Toja P, Michailidis G, Stramba-Badiale M, Cavagnini F (2006) Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients. Clin Endocrinol (Oxf) 65:626–630CrossRefGoogle Scholar
  19. 19.
    Vitale G, Pivonello R, Auriemma RS, Guerra E, Milone F, Savastano S, Lombardi G, Colao A (2005) Hypertension in acromegaly and in the normal population: prevalence and determinants. Clin Endocrinol (Oxf) 63:470–476CrossRefGoogle Scholar
  20. 20.
    Kartal I, Oflaz H, Pamukcu B, Meric M, Aral F, Ozbey N, Alagol F (2008) Investigation of early atherosclerotic changes in acromegalic patients. Int J Clin Pract 61:39–44Google Scholar
  21. 21.
    Otsuki M, Kasayama S, Yamamoto H, Saito H, Sumitani S, Kouhara H, Saitoh Y, Ohnishi T, Arita N (2001) Characterization of premature atherosclerosis of carotid arteries in acromegalic patients. Clin Endocrinol (Oxf) 54:791–796CrossRefGoogle Scholar
  22. 22.
    Sakai H, Tsuchiya K, Nakayama C, Iwashima F, Izumiyama H, Doi M, Yoshimoto T, Tsujino M, Yamada S, Hirata Y (2008) Improvement of endothelial dysfunction in acromegaly after transsphenoidal surgery. Endocr J 55:853–859PubMedCrossRefGoogle Scholar
  23. 23.
    Sze L, Schmid C, Bloch KE, Bernays R, Brandle M (2007) Effect of transsphenoidal surgery on sleep apnoea in acromegaly. Eur J Endocrinol 156:321–329PubMedCrossRefGoogle Scholar
  24. 24.
    Davi’ MV, Dalle Carbonare L, Giustina A, Ferrari M, Frigo A, Lo Cascio V, Francia G (2008) Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease. Eur J Endocrinol 159:533–540PubMedCrossRefGoogle Scholar
  25. 25.
    Kreutzer J, Vance ML, Lopes MB, Laws ER Jr (2001) Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 86:4072–4077PubMedCrossRefGoogle Scholar
  26. 26.
    Minniti G, Moroni C, Jaffrain-Rea ML, Esposito V, Santoro A, Affricano C, Cantore G, Tamburrano G, Cassone R (2001) Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients. Clin Endocrinol (Oxf) 55:307–313CrossRefGoogle Scholar
  27. 27.
    De Marinis L, Bianchi A, Mazziotti G, Mettimano M, Milardi D, Fusco A, Cimino V, Maira G, Pontecorvi A, Giustina A (2008) The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly. Pituitary 11:13–20PubMedCrossRefGoogle Scholar
  28. 28.
    Colao A, Pivonello R, Galderisi M, Cappabianca P, Auriemma RS, Galdiero M, Cavallo LM, Esposito F, Lombardi G (2008) Impact of treating acromegaly first with surgery or somatostatin analogs on cardiomyopathy. J Clin Endocrinol Metab 93:2639–2646PubMedCrossRefGoogle Scholar
  29. 29.
    Main G, Borsey DQ, Newton RW (1988) Successful reversal of sleep apnoea syndrome following treatment for acromegaly, confirmed by polygraphic studies. Postgrad Med J 64:945–946PubMedCrossRefGoogle Scholar
  30. 30.
    Saeki N, Isono S, Nishino T, Iuchi T, Yamaura A (1999) Sleep-disordered breathing in acromegalics–relation of hormonal levels and quantitative sleep study by means of bedside oximeter. Endocr J 46:585–590PubMedCrossRefGoogle Scholar
  31. 31.
    Pelttari L, Polo O, Rauhala E, Vuoriluoto J, Aitasalo K, Hyyppa MT, Kronholm E, Irjala K, Viikari J (1995) Nocturnal breathing abnormalities in acromegaly after adenomectomy. Clin Endocrinol (Oxf) 43:175–182CrossRefGoogle Scholar
  32. 32.
    Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A (2009) Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 94:1509–1517PubMedCrossRefGoogle Scholar
  33. 33.
    Smith WH, Nair RU, Adamson D, Kearney MT, Ball SG, Balmforth AJ (2005) Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts. J Endocrinol 187:379–386PubMedCrossRefGoogle Scholar
  34. 34.
    Maison P, Tropeano AI, Macquin-Mavier I, Giustina A, Chanson P (2007) Impact of somatostatin analogs on the heart in acromegaly. A meta-analysis. J Clin Endocrinol Metab 92:1743–1747PubMedCrossRefGoogle Scholar
  35. 35.
    Colao A, Marzullo P, Cuocolo A, Spinelli L, Pivonello R, Bonaduce D, Salvatore M, Lombardi G (2003) Reversal of acromegalic cardiomyopathy in young but not in middle-aged patients after 12 months of treatment with the depot long-acting somatostatin analogue octreotide. Clin Endocrinol (Oxf) 58:169–176CrossRefGoogle Scholar
  36. 36.
    Colao A, Marzullo P, Ferone D, Spinelli L, Cuocolo A, Bonaduce D, Salvatore M, Boerlin V, Lancranjan I, Lombardi G (2000) Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab 85:3132–3140PubMedCrossRefGoogle Scholar
  37. 37.
    Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Florimonte L, Salvatore M, Lombardi G (1999) Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly. J Clin Endocrinol Metab 84:17–23PubMedCrossRefGoogle Scholar
  38. 38.
    Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Della Morte AM, Pivonello R, Salvatore M, Lombardi G (2001) Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance. J Clin Endocrinol Metab 86:1551–1557PubMedCrossRefGoogle Scholar
  39. 39.
    Lombardi G, Colao A, Marzullo P, Biondi B, Palmieri E, Fazio S (2002) Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study. J Endocrinol Invest 25:971–976PubMedGoogle Scholar
  40. 40.
    Colao A, Ferone D, Cappabianca P, Basso Del, de Caro ML, Marzullo P, Monticelli A, Alfieri A, Merola B, Cali A, de Divitiis E, Lombardi G (1997) Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 82:3308–3314PubMedCrossRefGoogle Scholar
  41. 41.
    Gunal AI, Isik A, Celiker H, Eren O, Celebi H, Gunal SY, Luleci C (1996) Short term reduction of left ventricular mass in primary hypertrophic cardiomyopathy by octreotide injections. Heart 76:418–421PubMedCrossRefGoogle Scholar
  42. 42.
    Lombardi G, Colao A, Ferone D, Marzullo P, Landi ML, Longobardi S, Iervolino E, Cuocolo A, Fazio S, Merola B, Sacca L (1996) Cardiovascular aspects in acromegaly: effects of treatment. Metabolism 45:57–60PubMedCrossRefGoogle Scholar
  43. 43.
    Ip MS, Tan KC, Peh WC, Lam KS (2001) Effect of Sandostatin® LAR® on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity. Clin Endocrinol (Oxf) 55:477–483CrossRefGoogle Scholar
  44. 44.
    Herrmann BL, Wessendorf TE, Ajaj W, Kahlke S, Teschler H, Mann K (2004) Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly. Eur J Endocrinol 151:309–315PubMedCrossRefGoogle Scholar
  45. 45.
    Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146:707–716PubMedCrossRefGoogle Scholar
  46. 46.
    Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ (2002) Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev 23:623–646PubMedCrossRefGoogle Scholar
  47. 47.
    Brue T (2009) ACROSTUDY: status update on 469 patients. Horm Res 71(Suppl 1):34–38PubMedCrossRefGoogle Scholar
  48. 48.
    Pivonello R, Galderisi M, Auriemma RS, De Martino MC, Galdiero M, Ciccarelli A, D’Errico A, Kourides I, Burman P, Lombardi G, Colao A (2006) Treatment with GH receptor antagonist in acromegaly: effect on cardiac structure and performance. J Clin Endocrinol Metab 92:476–482PubMedCrossRefGoogle Scholar
  49. 49.
    Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Burman P, Kourides IA, Strasburger CJ, Lombardi G (2006) Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol 154:467–477PubMedCrossRefGoogle Scholar
  50. 50.
    Cozzi R, Attanasio R, Lodrini S, Lasio G (2004) Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf) 61:209–215CrossRefGoogle Scholar
  51. 51.
    Bogazzi F, Manetti L, Raffaelli V, Lombardi M, Rossi G, Martino E (2008) Cabergoline therapy and the risk of cardiac valve regurgitation in patients with hyperprolactinemia: a meta-analysis from clinical studies. J Endocrinol Invest 31:119–1123Google Scholar
  52. 52.
    Colao A (2008) The GH/IGF axis and the cardiovascular system: clinical implications. Clin Endocrinol (Oxf) 69:347–358CrossRefGoogle Scholar
  53. 53.
    Baldelli R, Ferretti E, Jaffrain-Rea ML, Iacobellis G, Minniti G, Caracciolo B, Moroni C, Cassone R, Gulino A, Tamburrano G (1999) Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients. J Clin Endocrinol Metab 84:527–532PubMedCrossRefGoogle Scholar
  54. 54.
    Baldwin A, Cundy T, Butler J, Timmis AD (1985) Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation. Acta Endocrinol (Copenh) 108:26–30Google Scholar
  55. 55.
    Bogazzi F, Di Bello V, Palagi C, Donne MG, Di Cori A, Gavioli S, Talini E, Cosci C, Sardella C, Brogioni S, Mariani M, Martino E (2005) Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in acromegalic patients treated with somatostatin analogues: a prospective study. Clin Endocrinol (Oxf) 62:590–596CrossRefGoogle Scholar
  56. 56.
    Ciulla MM, Epaminonda P, Paliotti R, Barelli MV, Ronchi C, Cappiello V, Sartorio A, Buonamici V, Magrini F, Beck-Peccoz P, Arosio M (2004) Evaluation of cardiac structure by echoreflectivity analysis in acromegaly: effects of treatment. Eur J Endocrinol 151:179–186PubMedCrossRefGoogle Scholar
  57. 57.
    Colao A, Spinelli L, Cuocolo A, Spiezia S, Pivonello R, Di Somma C, Bonaduce D, Salvatore M, Lombardi G (2002) Cardiovascular consequences of early-onset growth hormone excess. J Clin Endocrinol Metab 87:3097–3104PubMedCrossRefGoogle Scholar
  58. 58.
    Colao A, Marzullo P, Lombardi G (2002) Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly. Eur J Endocrinol 146:303–309PubMedCrossRefGoogle Scholar
  59. 59.
    Jaffrain-Rea ML, Minniti G, Moroni C, Esposito V, Ferretti E, Santoro A, Infusino T, Tamburrano G, Cantore G, Cassone R (2003) Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly. Eur J Endocrinol 148:193–201PubMedCrossRefGoogle Scholar
  60. 60.
    Hayward RP, Emanuel RW, Nabarro JD (1987) Acromegalic heart disease: influence of treatment of the acromegaly on the heart. Q J Med 62:41–58PubMedGoogle Scholar
  61. 61.
    Hradec J, Kral J, Janota T, Krsek M, Hana V, Marek J, Malik M (1999) Regression of acromegalic left ventricular hypertrophy after lanreotide (a slow-release somatostatin analog). Am J Cardiol 83:1506–1509PubMedCrossRefGoogle Scholar
  62. 62.
    Lim MJ, Barkan AL, Buda AJ (1992) Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion. Ann Intern Med 117:719–726PubMedGoogle Scholar
  63. 63.
    Merola B, Cittadini A, Colao A, Ferone D, Fazio S, Sabatini D, Biondi B, Sacca L, Lombardi G (1993) Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly. J Clin Endocrinol Metab 77:790–793PubMedCrossRefGoogle Scholar
  64. 64.
    Padayatty SJ, Perrins EJ, Belchetz PE (1996) Octreotide treatment increases exercise capacity in patients with acromegaly. Eur J Endocrinol 134:554–559PubMedCrossRefGoogle Scholar
  65. 65.
    Pereira JL, Rodriguez-Puras MJ, Leal-Cerro A, Martinez A, Garcia-Luna PP, Gavilan I, Pumar A, Astorga R (1991) Acromegalic cardiopathy improves after treatment with increasing doses of octreotide. J Endocrinol Invest 14:17–23PubMedGoogle Scholar
  66. 66.
    Thuesen L, Christensen SE, Weeke J, Orskov H, Henningsen P (1989) The cardiovascular effects of octreotide treatment in acromegaly: an echocardiographic study. Clin Endocrinol (Oxf) 30:619–625CrossRefGoogle Scholar
  67. 67.
    Tokgozoglu SL, Erbas T, Aytemir K, Akalin S, Kes S, Oram E (1994) Effects of octreotide on left ventricular mass in acromegaly. Am J Cardiol 74:1072–1074PubMedCrossRefGoogle Scholar
  68. 68.
    Vianna CB, Vieira ML, Mady C, Liberman B, Durazzo AE, Knoepfelmacher M, Salgado LR, Ramires JA (2002) Treatment of acromegaly improves myocardial abnormalities. Am Heart J 143:873–876PubMedCrossRefGoogle Scholar
  69. 69.
    Colao A, Martino E, Cappabianca P, Cozzi R, Scanarini M, Ghigo E (2006) First-line therapy of acromegaly: a statement of the A.L.I.C.E. (Acromegaly primary medical treatment Learning and Improvement with Continuous Medical Education) Study Group. J Endocrinol Invest 29:1017–1020PubMedGoogle Scholar
  70. 70.
    Carlsen SM, Lund-Johansen M, Schreiner T, Aanderud S, Johannesen O, Svartberg J, Cooper JG, Hald JK, Fougner SL, Bollerslev J (2008) Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial. J Clin Endocrinol Metab 93:2984–2990PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Molecular and Clinical Endocrinology and Oncology, Section of EndocrinologyFederico II University of NaplesNaplesItaly

Personalised recommendations