Acromegalic heart disease
Description, Causes and Risk Factors:
Acromegaly is a serious condition that occurs when the body produces too much of the hormones that control growth. The hormone most often affected is called growth hormone, or GH. It is produced by the pituitary gland, a tiny organ at the base of the brain. Growth hormone promotes growth of bone, cartilage, muscle, organs, and other tissues. When there is too much growth hormone in the body, these tissues grow larger than normal. This excessive growth can cause serious disease and even premature death.
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. 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. 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. 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.
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. 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. 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. This is a result of the stimulatory effects of GH and IGF-1 on myocardial contractility as mediated by changes in intracellular calcium. 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. However, at the advanced stages of untreated disease, cardiac abnormalities may rarely result in systolic dysfunction with manifestations of congestive heart failure.
Acromegaly is usually caused by excessive secretion of growth hormone by a pituitary macroadenoma or microadenoma. Other rare causes include increased growth hormone-releasing hormone (GHRH) from hypothalamic tumours, and ectopic GHRH or growth hormone from non-endocrine tumours, e.g. lung cancer, cancer of the pancreas, carcinoid tumours, medullary carcinoma of the thyroid.
Reserch: In a series of 256 patients with acromegaly, 10 had evidence of heart disease for which no explanation apart from the acromegaly could be found. Heart disease presented with effort dyspnea, cardiac failure, palpitation, ECG changes or cardiomegaly. Initial chest radiographs showed cardiac enlargement in seven patients. Electrocardiograms were abnormal in nine patients with repolarization disorders or intraventricular conduction defects. disturbances were found in six. Echocardiograms were performed on six patients; all were abnormal showing left ventricular hypertrophy or impaired function. In five patients radionuclide ventriculography was also performed. Cardiac catheterisation was undertaken on seven patients; all showed either hypertrophy or dilatation of the left ventricle. Coronary arteries were widely dilated in two patients and in another there was dilation of the proximal segment only.
In six of the 10 patients, acromegaly was cured by transsphenoidal surgery. This resulted in limited improvement of cardiac function in two patients only. Of the four patients who were not cured, three died and one was lost to the study. Four patients in total died and autopsies were obtained in two: one showed changes suggesting myocarditis and the other diffuse fibrosis. It is concluded that acromegaly may infrequently lead to h