The Heart in Acromegaly

September 1, 2010

By Ari Pollack, MD

Faculty Peer Reviewed

The onset of acromegaly is subtle, and its progression is usually very slow. In fact, the usual interval from the onset of symptoms until diagnosis is about twelve years.[1] The manifestations of acromegaly result from excessive secretion of growth hormone (GH), which targets the liver, resulting in stimulation of hepatic secretion of insulin-like growth factor-1 (IGF-1), which causes many of the clinical manifestations of acromegaly.  The most common cause of acromegaly is a functional pituitary adenoma.[2] The effects of excess GH and IGF-1 secretion include the growth of many tissues, including skin, connective tissue, cartilage, bone, viscera, and many epithelial tissues.  There are also metabolic consequences such as insulin antagonism and lipolysis. The local mass effect of the adenoma can lead to symptoms of headache, cranial nerve defects, and visual field defects, specifically bitemporal hemianopsia.[3] The mortality rate of patients with acromegaly appears to be increased and is primarily from cardiovascular disease, a risk that may be reversed by curing the disease.[2]

The GH/IGF-1 axis has a direct endocrine effect on the myocardium, resulting in hypertrophy, enhancement of contractile performance, and elongation of the action potential of cardiac fibers.[4] Ultimately, the involvement of the heart in acromegaly is characterized by concentric biventricular hypertrophy. Structural changes of the heart can even occur in patients briefly exposed to GH hypersecretion.[5] This remodeling is further enhanced by the hypertension and glucose intolerance commonly present in the acromegalic patient.  The evolution of cardiomyopathy in acromegaly is characterized by significant worsening of the heart’s ability to function as an efficient pump.  In patients with short disease duration, there is initial cardiac hypertrophy with increased heart rate, contractility, and cardiac output, termed the hyperkinetic syndrome.[4] This is a result of the stimulatory effects of GH and IGF-1 on myocardial contractility as mediated by changes in intracellular calcium.[4] As hypertrophy becomes more prominent, diastolic dysfunction may develop, leading to the development of heart failure with preserved ejection fraction.  Fortunately, the clinical syndrome of heart failure is uncommon (~3%) in patients with acromegaly with either a normal or reduced ejection fraction.[6] However, at the advanced stages of untreated disease, cardiac abnormalities may rarely result in systolic dysfunction with manifestations of congestive heart failure.

Cardiovascular disease is not limited to structural abnormalities in patients with acromegaly.  There is also valvular disease, including mitral regurgitation, aortic regurgitation and tricuspid regurgitation seen in the late stages of acromegaly as a result of ventricular remodeling, as well as increased potential for arrhythmias.[4] The mechanism behind the predisposition for dysrhythmic events involves phenotypic changes in membrane proteins, conduction system disease,[4] and structural uncoupling of cardiac myocytes resulting in an increased number of re-entrant events.  Compared to controls, individuals with acromegaly have a higher prevalence of ectopic beats, paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, sick sinus syndrome, ventricular tachycardia, and bundle branch blocks.[7]

The data regarding a direct relationship between the development of coronary artery disease and acromegaly are limited.  Given the frequency of hypertension and diabetes seen with the syndrome, it is likely that patients with acromegaly are at increased risk for developing atherosclerosis.  In terms of the direct effect of GH and IGF-1 on atherosclerosis development, the evidence suggests that it is largely the hypertension and diabetes  associated with acromegaly that predispose patients to the development of atherosclerotic disease.  It is known that GH and IGF-1 cause direct endothelial dysfunction with subsequent decreased vasodilatory capacity, which may have implications for susceptibility to vascular events.[5] In terms of the reversibility of acromegalic cardiomyopathy, suppression of GH and IGF-1 has been shown to be efficacious in improving diastolic function by virtue of reducing left ventricular mass.  However, the effect on systolic function and exercise tolerance are variable and depends largely on the length of exposure to GH and IGF-1, as well as the co-morbidities of acromegaly, including hypertension and diabetes.[8]

It is important to note that the cardiac implications of acromegaly are a result of excessive secretion of GH and IGF-1 and that these hormones play an important role in cardiac development when present at normal physiologic levels.  In fact, patients with GH deficiency, whether childhood- or adult-onset, suffer from structural cardiac abnormalities, including narrowing of cardiac walls and functional impairment, with resultant reduction in diastolic filling and reduced left ventricular response to peak exercise.[9] As in the acromegalic heart, these cardiac abnormalities are partially reversible with GH supplementation.[9] Additionally, attention has been focused on the efficacy of GH to increase cardiac mass and function in chronic non-endocrine-related heart failure including ischemic and idiopathic cardiomyopathies, thereby illustrating the dichotomy between the potential beneficial effects of exogenous GH in carefully selected patients and the disadvantageous effects of excess GH secretion in patients with acromegaly.

Dr. Pollack, Class of 2010, NYU School of Medicine

Peer reviewed by Alex Reyentovich, MD, Cardiology, NYU School of Medicine

Image courtesy of Wikimedia Commons.

References:

[1]  Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004; 25(1):102-152.

[2]  Melmed S. Medical progress: Acromegaly. N Engl J Med. 2006;355(24):2558-2573.

[3]  Molitch ME. Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am. 1992;21(3):597-614.

[4]  Lombardi G, Galdiero M, Auriemma RS, Pivonello R, Colao A. Acromegaly and the cardiovascular system. Neuroendocrinology. 2006;83(3-4):211-217.

[5]  Vitale G, Pivonello R, Lombardi G, Colao A. Cardiac abnormalities in acromegaly: pathophysiology and implications for management.  Treat Endocrinology. 2004;3(5):309-318.

[6]  Bihan H, Becker KL, Snider RH, Nylen E, et al. Long-term outcome of patients with acromegaly and congestive heart failure. J Clin Endocrinol Metab. 2004;89(11):5308-5313.

[7]  Kahaly G, Olshausen KV, Mohr-Kahaly S, et al.  Arrhythmia profile in acromegaly.  Eur Heart J. 1992;13(1):51-56.

[8]  Colao A, Cuocolo A, Marzullo P, et al. Is the acromegalic cardiomyopathy reversible?  Effects of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance.  J Clin Endocrinol Metab. 2001;86(4):1551-1557.

[9]  Colao A, Marzullo P, Di Somma C, Lombardi G. Growth hormone and the heart.  Clin Endocrinol (Oxf). 2001;54(2):137-154.

2 Responses to The Heart in Acromegaly

  1. Brian Newhart on September 12, 2014 at 12:33 am

    Thank you for your informative article. I am a 58 yo male that had my 3 cm
    Pituatary adnoma removed in 1998. Continued treatment with sandostatin lar for
    5 years brought the igf-1 into the normal range.
    Effects of the acromegaly. Stenosis in cervical and lumbar spine. Left and right shoulder joint replacement due to accelerated osteoarthritis. Thoracic aorta root dilation. Hypertension, type II diabetes. Right bundle branch block. I hope future research will detect this disease process earlier. I made it 33 years as an airline pilot before my systems started breaking Down.

  2. Desert Tripper on September 26, 2014 at 9:56 pm

    I too have had quite a ride from this rare and strange condition. In addition to CHF I have experienced carpal tunnel syndrome, sleep apnea, arthritis in my shoulders and lower back, and seen my shoe size go from 10 1/2 to 13. Didn’t get diagnosed until I had a bout of Hodgkin’s lymphoma – the 3cm pituitary adenoma showed up on a CAT scan of my head and neck. No known correlation between acromegaly and Hodgkin’s but the timing couldn’t have been worse! Cancer treatment messed up my heart even more – one of the chemo drugs, adriamycin, is notorious for its damaging effect on the heart. I’m sure the radiation didn’t help it either, though thankfully my cancer is in remission. During a period of unemployment, I had considered a career as a long distance trucker but was continually hounded by DMV/DOT for my sleep apnea until I decided to give that up. (Good thing they didn’t know about all the rest going on!) Feel like I’m kind of living on borrowed time now even though I’m not yet 50. Neurosurgery coming up in the next few months. Also looking forward to new CHF meds in the next several years.

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