Malignant ventricular tachycardia in acromegaly: a case report

ABSTRACT CONTEXT: In patients with acromegaly, cardiovascular complications are the main cause of death; sudden death has been associated with ventricular tachyarrhythmias. In other patients with life-threatening malignant ventricular tachyarrhythmias, surgical placement of an implantable cardioverter-defibrillator (ICD) has proved highly effective in reducing sudden death rates. CASE REPORT: The present article reports the case of a 50-year-old male acromegalic patient who presented symptoms of syncope induced by ventricular tachycardia. An ICD was surgically implanted and a pituitary adenoma, which was responsible for the acromegaly, was completely removed in the same procedure. The surgery was successful and the ventricular arrhythmias were effectively terminated. During six months of follow-up, no documented arrhythmic episodes occurred. CONCLUSION: In patients with acromegaly, malignant ventricular tachyarrhythmia might be effectively controlled by implantation of an ICD and surgical removal of the pituitary adenoma.


INTRODUCTION
Acromegaly is characterized by hypersecretion of growth hormone, which in more than 95% of patients is caused by a secreting pituitary tumor. 1 The high prevalence of arrhythmias and sudden cardiac death in these patients may be related to myocardial interstitial fibrosis. 2veral clinical studies have reported the presence of premature ventricular contractions, 3 third-degree atrioventricular block 4,5 and dilated cardiomyopathy 6 in patients with acromegaly.However, in a review of the literature regarding case reports on malignant ventricular tachyarrhythmia concomitant with hemodynamic instability and acromegaly, only one case was found.In 2010, Yokota et al. reported that a 51-year-old man with a diagnosis of cardiac dysfunction with acromegaly was successfully treated by means of transsphenoidal surgery and normalization of growth hormone and insulin-like growth factor-1 (IGF-1), even in the presence of severe fibrosis in the myocardium. 7In the present report, we describe a case of an acromegalic patient with recurrent ventricular tachyarrhythmia who underwent placement of an implantable cardioverter-defibrillator (ICD) and pituitary adenoma surgery.By searching in Medline (via PubMed), Embase and Lilacs, with the search strategies shown in Table 1, only one case report 7 was found, similar to ours.

CASE REPORT
A 50-year-old Han Chinese man was admitted to our hospital after several episodes of syncope during the previous week, with electrocardiographic evidence of monomorphic ventricular tachycardia.
On physical examination, increased head circumference, pronounced lower jaw protrusion with macroglossia and swelling of the soft tissues in the hands and feet were evident (Figure 1).
Serum levels of growth hormone and serum insulin-like growth factor-1 (IGF-1) were elevated, reaching 40 and 368 ng/ml, respectively.The concentration of serum brain natriuretic peptide (BNP) was 2640 pg/ml.The patient's medical history was remarkable because of the presence of systemic hypertension over the past five years, which had not been treated regularly by antihypertensive drugs.His daily blood pressure range was from 150/90 to 160/100 mmHg.Blood tests on admission revealed that the patient's serum levels of estradiol, luteinizing hormone, prolactin and follicle-stimulating hormone were within normal values.
Cerebral magnetic resonance imaging (MRI) revealed an intrasellar mass lesion, suggestive of definitive presence of a pituitary adenoma (Figure 2).The size and shape of his skull were increased.Scattered spots and flaky hyperintensity in T1 and T2,  A dual-coil lead ICD defibrillator (Medtronic Marquis DR 7274) was implanted and a 50-mg dose of metoprolol succinate was administered twice per day.Transsphenoidal surgical resection of a pituitary adenoma was performed after the ICD implantation.
During six months of follow-up, no documented episodes of syncopal ventricular arrhythmia occurred.

DISCUSSION
The risk of cardiovascular diseases is directly associated with elevated serum levels of growth hormone and prolonged clinical course.Chronic excessive growth hormone and IGF-1 secretion in acromegaly cases affects cardiac morphology and performance, thereby inducing cardiomyopathy specific to this disease. 9,10The early stage of acromegaly is characterized by hyperkinetic syndrome.Frequently, if the disease is untreated for many years or unsuccessfully treated at the early stage, concentric hypertrophy and diastolic dysfunction can develop.As the disease progresses to advanced stages, valve disease and impaired systolic and diastolic performance may occur.The pathological characteristics of acromegalic cardiomyopathy include interstitial fibrosis, myocyte apoptosis, and lymphocyte infiltration.The development of ventricular dysfunction and progression to cardiac failure may be related to increased myocyte apoptosis.The presence of myocardial fibrosis may be responsible for slowdown and non-homogeneity of propagation of action potentials, 11,12 which induces ventricular arrhythmias.
Acromegalic patients often complain of various initial symptoms relating to cardiovascular or metabolic complications.Cardiovascular complications are common and account for as much as 60% of the mortality in acromegaly cases.Malignant ventricular tachyarrhythmias are commonly concomitant with recurrent syncope and are often a contributing factor in sudden cardiac death in acromegalic patients, even in those with an apparently normal heart. 13Therefore, when occurrences of clinical arrhythmias and heart failure are not easily explained by cardiogenic causes, it seems reasonable to consider the possibility of acromegaly-associated cardiovascular complications.
Hidden symptoms and slow clinical progression make acromegaly difficult to diagnose, particularly in the early stages.
For this patient, ventricular tachyarrhythmia was definitively identified on admission, but its etiology was unclear.The possibility of acromegaly makes it extremely important to identify the specific heart disease responsible for arrhythmia when it occurs.
In this case, echocardiographic examination did not meet all the diagnostic criteria for dilated cardiomyopathy, although dilated cardiomyopathy may cause arrhythmia.
After careful physical examination, the typical signs of acromegaly in this case were identified.Moreover, cerebral MRI revealed the presence of an intracranial pituitary adenoma, and blood tests indicated that the serum level of growth hormone was elevated.
Presence of a pituitary adenoma is responsible for excessive levels of growth hormone, which leads to acromegalic cardiomyopathy.Cardiovascular complications might benefit from treatment directed towards the pituitary adenoma, and lowering the blood growth hormone levels might arrest further progression of myocardial hypertrophy. 14Bromocriptine inhibits release and synthesis of prolactin by acting directly on the prolactin-secreting cells of the anterior pituitary. 15In patients with acromegaly, bromocriptine treatment results in reduction of serum growth hormone levels, 16 which consequently blocks the unfavorable effect of growth hormone on the heart.
Several studies have found that early heart attack could be effectively controlled after successful treatment of pituitary tumors, 17,18 thus indicating that early-stage cardiovascular complications are reversible.For example, recent evidence has shown that normalization of growth hormone and IGF-1 can work even in the presence of severe fibrosis in the myocardium. 7However, whether end-stage acromegalic cardiomyopathy is reversible is unknown.Unexpectedly, in the present case with end-stage acromegalic cardiomyopathy, after the resection of the pituitary adenoma, no arrhythmic episodes occurred during six months of follow-up.

CONCLUSION
Malignant ventricular tachyarrhythmia might be effectively controlled by implantation of an ICD, surgical removal of a pituitary adenoma and oral drug therapy.

Table 1 .Figure 1 .
Figure 1.The patient exhibited the typical features of acromegaly, with increased head circumference and pronounced lower jaw protrusion.

Figure 2 .
Figure 2. Findings from cerebral magnetic resonance imaging (MRI).An enlarged pituitary gland (arrowhead) appeared as a mass-like region with heterogeneous signal intensity and focal hyperintensity.

Figure 3 .
Figure 3. Findings from the electrophysiological test.Ventricular tachycardia found from electrocardiogram.