Abstract
Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully treated, concentric biventricular hypertrophy and diastolic dysfunction can develop and, at least, lead to diastolic congestive heart failure. Rhythm disturbances and valve dysfunction are also frequently described in acromegaly. The coexistence of other complications, such as diabetes and arterial hypertension, can induce the worsening of acromegalic cardiomyopathy. Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction. In conclusion, an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory in acromegaly.
References
1.
Colao A, Merola B, Ferone D, Lombardi G: Acromegaly. J Clin Endocrinol Metab 1997;82:2777–2781.
2.
Colao A, Ferone D, Marzullo P, Lombardi G: Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004;25:102–152.
3.
Colao A, Marzullo P, Di Somma C, Lombardi G: Growth hormone and the heart. Clin Endocrinol (Oxf) 2001;54:137–154.
4.
Hejtmancik MR, Bradfield JY, Herrmann GR: Acromegaly and the heart: a clinical and pathologic study. Ann Intern Med 1951;34:1445–1456.
5.
López-Velasco R, Escobar-Morreale HF, Vega B, Villa E, Sancho JM, Moya-Mur JL, Garcia-Robles R: Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension. J Clin Endocrinol Metab 1997;82:1047–1053.
6.
Colao A, Baldelli R, Marzullo P, Ferretti E, Ferone D, Gargiulo P, Petretta M, Tamburrano G, Lombardi G, Liuzzi A: Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy. J Clin Endocrinol Metab 2000;85:193–199.
7.
Kahaly G, Olshausen KV, Mohr-Kahaly S, Erbel R, Boor S, Beyer J, Meyer J: Arrhythmia profile in acromegaly. Eur Heart J 1992;13:51–56.
8.
Colao A, Spinelli L, Marzullo P, Pivonello R, Petretta M, Di Somma C, Vitale G, Bonaduce D, Lombardi G: High prevalence of cardiac valve disease in acromegaly: an observational analytical prospective case-control study. J Clin Endocrinol Metab 2003;88:3196–3201.
9.
Mandinov L, Eberli FR, Seiler C, Hess OM: Diastolic heart failure. Cardiovasc Res 2000;45:813–825.
10.
Isgaard J, Nilsson A, Vikman K, Isaksson OGP: Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle. J Endocrinol 1989;120:107–112.
11.
Delafontaine P: Insulin-like growth factor I and its binding proteins in the cardiovascular system. Cardiovasc Res 1995;30:825–834.
12.
Freestone NS, Ribaric S, Mason WT: The effect of insulin-like growth factor-1 on adult rat cardiac contractility. Mol Cell Biochem 1996;163:223–229.
13.
Rubin SA, Buttrick P, Malhotra A, Melmed S, Fishbein MC: Cardiac physiology, biochemistry and morphology in response to excess growth hormone in the rat. J Mol Cell Cardiol 1990;22:429–438.
14.
Timsit J, Riou B, Bertherat J, Wisnewsky C, Kato NS, Weisberg AS, Lubetzki J, Lecarpentier Y, Winegrad S, Mercadier JJ: Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern and myosin-adenosin thriphosphatase activity of rat left ventricle. J Clin Invest 1990;86:507–515.
15.
Strömer H, Cittadini A, Douglas PS, Morgan JP: Exogenously administered growth hormone and insulin-like growth factor-1 alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart. Circ Res 1996;79:227–235.
16.
Colao A, Spinelli L, Cuocolo A, Spiezia S, Bonaduce D, Salvatore M, Lombardi G: Cardiovascular consequences of early-onset growth hormone excess. J Clin Endocrinol Metab 2002;87:3097–3104.
17.
Marzullo P, Cuocolo A, Ferone D, Pivonello R, Salvatore M, Lombardi G, Colao A: Cardiac effect of thyrotoxicosis in acromegaly. J Clin Endocrinol Metab 2000;85:1426–1432.
18.
Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Della Morte AM, Petretta M, Salvatore M, Lombardi G: Impact of patient’s age and disease duration on cardiac performance in acromegaly: a radionuclide angiography study. J Clin Endocrinol Metab 1999;84:1518–1523.
19.
Fazio S, Cittadini A, Cuocolo A, Merola B, Sabatini D, Nicolai E, Colao A, Biondi B, Lombardi G, Saccà L: Impaired cardiac performance is a distinct feature of uncomplicated acromegaly. J Clin Endocrinol Metab 1994;79:441–446.
20.
Harjai KJ: Potential new cardiovascular risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen. Ann Intern Med 1999;131:376–386.
21.
Rodrigues EA, Caruana MP, Lahiri A, Nabarro JD, Jacobs HS, Raftery EB: Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle. Br Heart J 1989;62:185–194.
22.
Hermann BL, Bruch C, Saller B, Ferdin S, Dagres N, Ose C, Erbel R, Mann K: Occurrence of ventricular late potentials in patients with active acromegaly. Clin Endocrinol (Oxf) 2001;55:201–207.
23.
Vitale G, Pivonello R, Auriemma RS, Guerra E, Milone F, Savastano S, Lombardi G, Colao A: Hypertension in acromegaly and in the normal population: prevalence and determinants. Clin Endocrinol (Oxf) 2005;63:470–476.
24.
Chanson P, Megnien JL, del Pino M, Coirault C, Merli I, Houdouin L, Harris AG, Levenson J, Lecarpentier Y, Simon A, Chemla D: Decreased regional blood flow in patients with acromegaly. Clin Endocrinol (Oxf) 1998;49:725–731.
25.
Folkow B: Physiological aspects of primary hypertension. Physiol Rev 1982;62:347–504.
26.
Dilley RJ, Schwartz SM: Vascular remodeling in the growth hormone transgenic mouse. Circ Res 1989;65:1233–1240.
27.
Schiavon F, Maffei P, Martini C, De Carlo E, Fais C, Todesco S, Sicolo N: Morphologic study of microcirculation in acromegaly by capillaroscopy. J Clin Endocrinol Metab 1999;84:3151–3155.
28.
Colao A, Spiezia S, Cerbone G, Pivonello R, Marzullo P, Ferone D, Di Somma C, Assanti AP, Lombardi G: Increased arterial intima-media thickness by B-M mode echo-Doppler ultrasonography in acromegaly. Clin Endocrinol (Oxf) 2001;54:515–524.
29.
Sowers JR, Standley PR, Ram JL, Jacober S: Hyperinsulinemia, insulin resistance, and hyperglycemia: contributing factors in the pathogenesis of hypertension and atherosclerosis. Am J Hypertens 1993;6:260S–270S.
30.
Colao A, Marzullo P, Lombardi G, the Multicenter Italian Study Group on Lanreotide: Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly. Eur J Endocrinol 2002;146:303–309.
31.
Maison P, Demolis P, Young J, Schaison G, Giudicelli JF, Chanson P: Vascular reactivity in acromegalic patients: preliminary evidence for regional endothelial dysfunction and increased sympathetic vasoconstriction. Clin Endocrinol (Oxf) 2000;53:445–451.
32.
Brevetti G, Marzullo P, Silvestro A, Pivonello R, Oliva G, Di Somma C, Lombardi G, Colao A: Early vascular alterations in acromegaly. J Clin Endocrinol Metab 2002;87:3174–3179.
33.
Minniti G, Moroni C, Jaffrain-Rea ML, Esposito V, Santoro A, Affricano C, Cantore G, Tamburrano G, Cassone R: Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients. Clin Endocrinol (Oxf) 2001;55:307–313.
34.
Baldelli R, Ferretti E, Jaffrain-Rea ML, Iacobellis G, Minniti G, Caracciolo B, Moroni C, Cassone R, Gulino A, Tamburrano G: Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog in acromegalic patients. J Clin Endocrinol Metab 1999;84:527–532.
35.
Colao A, Marzullo P, Ferone D, Spinelli L, Cuocolo A, Bonaduce D, Salvatore M, Boerlin V, Lancranjan I, Lombardi G: Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab 2000;86:3132–3140.
36.
Thuesen L, Christensen SE, Weeke J, Orskov H, Henningsen P: The cardiovascular effects of octreotide treatment in acromegaly: an echocardiographic study. Clin Endocrinol (Oxf) 1989;30:619–625.
37.
Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Florimonte L, Salvatore M, Lombardi G: Effects of one-year treatment with octreotide on cardiac performance in patients with acromegaly. J Clin Endocrinol Metab 1999;84:17–23.
38.
Colao A, Marzullo P, Cuocolo A, Spinelli L, Landi ML, Bonaduce D, Salvatore M, Lombardi G: 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) 2003;58:169–176.
39.
Lombardi G, Colao A, Marzullo P, Biondi B, Palmieri E, Fazio S, Multicenter Italian Study Group on Lanreotide: Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced growth hormone and insulin-like growth factor-I decrease in acromegaly: a prospective multicenter study. J Endocrinol Invest 2002;25:971–976.
40.
Colao A, Ferone D, Cappabianca P, de Caro ML, Marzullo P, Monticelli A, Alfieri A, Merola B, Calì A, de Divitiis E, Lombardi G: Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 1997;82:3308–3314.
41.
Herrington AM, George KW, Moulds CC: Octreotide-induced bradycardia. Pharmacotherapy 1998;18:413–416.
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2006
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