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Power Failure: Acromegalic Cardiomyopathy

2016; Elsevier BV; Volume: 129; Issue: 7 Linguagem: Inglês

10.1016/j.amjmed.2016.02.041

1555-7162

Neha Mantri, Ezra A. Amsterdam, Marilyn Tan, Gagan D. Singh,

Glycogen Storage Diseases and Myoclonus

During his college years, the patient, at 6 ft, 8 in and 280 lb, aroused the attention of professional basketball scouts. But exertional fatigue and shortness of breath truncated his athletic aspirations. These symptoms continued in the ensuing years, necessitating approximately 15 hospitalizations at outside institutions for progressive dyspnea. No discernible etiology was established on any of these occasions. Now 35 years old, he presented to the Emergency Department reporting chronic shortness of breath, chest pain, and fatigue, symptoms of heart failure that had plagued him repeatedly in the past. The patient was African American. He had no history of smoking, alcohol consumption, or illicit drug use. His family history was unremarkable. Because his medical care had been staggered, he was unable to provide definitive details about any of the therapeutic regimens he followed in the past or his compliance with them. Upon arrival, the patient was in moderate respiratory distress and was speaking in 3-word sentences. He was afebrile, his pulse rate was 85 beats per minute, his blood pressure was 193/111 mm Hg, his respiratory rate was 24 breaths per minute, and his oxygen saturation was 97% on 4 L of oxygen by nasal cannula. Physical examination disclosed frontal bossing, enlarged hands and feet, doughy skin texture, prominent skin tags, acanthosis nigricans around his neckline, and macroglossia (Figure 1). His jugular venous pressure was 12 cm, his lungs had diffuse crackles bilaterally, and the cardiac point of maximum impulse was laterally displaced. His cardiac rhythm was irregularly irregular; no murmurs, rubs, or gallops were evident, and 3+ pitting edema was noted below his knees, bilaterally. Laboratory data were as follows: leukocytes, 4.3 × 103 cells/mm3; hemoglobin, 13 g/dL; glucose, 81 mg/dL; troponin I, 0.11 ng/mL (reference, 4 mm in diameter) coronary arteries.Figure 3(A) A 2-dimensional transthoracic echocardiogram, parasternal long-axis view, demonstrated concentric left ventricular hypertrophy and massive dilation of the left atrium (LA). (B) This 2-dimensional apical 4-chamber view also identified considerable enlargement of the left atrium. (C) In comparison with our patient's 2-dimensional transthoracic echocardiogram, parasternal long-axis view, this similar view from a healthy person displays normal anatomy. (D) A 2-dimensional apical 4-chamber view from a person with normal results is shown. Consider the difference in magnitude of scale (arrows) between our patient (A, B) vs a person with normal structures (C, D). Distance between the scale markers is 10 mm. LV = left ventricle.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The findings pointed toward a diagnosis of acromegaly and associated cardiomyopathy. Further test results included growth hormone, 17.8 ng/mL (reference, 0.05-3 ng/mL), and for 2 separate samples, insulin-like growth factor-1, 700 and 771 ng/mL (reference, 81-225 ng/mL). A complete endocrine evaluation indicated that the patient had low testosterone and normal levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and cortisol. Magnetic resonance imaging of the brain demonstrated a mild prominence at the left side of the pituitary gland, suggesting a 2-3-mm pituitary microadenoma. With additional questioning, the patient reported that his clothing and shoe sizes had increased over the previous decade; his shoe size went from 14 to 19, and he was unable to wear a cap on his head due to his enlarging forehead. This information further supported a diagnosis of acromegalic cardiomyopathy. Acromegaly is rare, with a prevalence of 40 cases per million people. Slowly progressive enlargement of the face and extremities is accompanied by cardiac, rheumatologic, respiratory, and metabolic derangements tied to elevations in circulating growth hormone and insulin-like growth factor-1.1Scacci M. Cavagnini F. Acromegaly.Pituitary. 2006; 9: 297-303Crossref PubMed Scopus (70) Google Scholar Characteristic structural changes include thickening of the heart muscle and dilation of the ventricles, which contribute to diminished diastolic function. Anatomical changes are compounded by common comorbidities: hypertension, dyslipidemia, and insulin resistance. Hypertension results from the sodium-retaining effects of growth hormone, inhibition of atrial natriuretic peptide by insulin-like growth factor-1, and the increased peripheral vascular resistance triggered by both hormones. Altered hormonal function also changes the sympatho-adrenomedullary pathway, promoting endothelial dysfunction, valvular disease, and acromegalic cardiomyopathy.2Colao A. Pivonello R. Grasso L.F. et al.Determinants of cardiac disease in newly diagnosed patients with acromegaly: results of a 10-year survey study.Eur J Endocrinol. 2011; 165: 713-721Crossref PubMed Scopus (67) Google Scholar In addition, excess growth hormone increases production of proinflammatory mediators that degrade structural elements of the aortic and mitral valves, precipitating regurgitation. Finally, progressive myocardial fibrosis and involvement of the cardiac conduction system increase the risk for arrhythmias and conduction disorders. Clinical manifestations of acromegalic cardiomyopathy depend on the degree and duration of cardiovascular dysfunction. Initially, cardiovascular dysfunction, propelled by the effects of growth hormone and insulin-like growth factor-1, is characterized by abnormally increased myocardial contractility and augmented cardiac output.3Isgaard J. Arcopinto M. Karason K. Cittadini A. GH and the cardiovascular system: an update on a topic at heart.Endocrine. 2015; 48: 25-35Crossref PubMed Scopus (96) Google Scholar This early aberration likely put our patient in a hyperkinetic state during his stint as a college athlete. But a decade later, in the absence of any treatment, his once-normal myocardium was marked by interstitial fibrosis, collagen deposition, myofib-rillar derangements, and monocyte necrosis, alterations that led to diastolic dysfunction and exertional intolerance. Unfortunately, most patients fail to present until the third and advanced stage of acromegalic cardiomyopathy, when systolic dysfunction is superimposed on the preceding abnormalities, resulting in congestive heart failure.4Vitale G. Pivonello R. Lombardi G. Colao A. Cardiac abnormalities in acromegaly. Pathophysiology and implications for management.Treat Endocrinol. 2004; 3: 309-318Crossref PubMed Scopus (31) Google Scholar Ambulatory monitoring demonstrates complex ventricular arrhythmias in about 50% of all patients with acromegalic cardiomyopathy.5Jayasena C.N. Comninos A.N. Clarke H. Donaldson M. Meeran K. Dhillo W.S. The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular, and metabolic comorbidities in treated patients with acromegaly.Clin Endocrinol (Oxf). 2011; 75: 220-225Crossref PubMed Scopus (48) Google Scholar The lack of timely diagnosis in our patient led to numerous hospital admissions over a decade for congestive heart failure, each treated independently without identification of the primary etiology. If the patient's clinical presentation suggests acromegalic cardiomyopathy, laboratory studies must be performed to confirm the diagnosis. Once suspicions are substantiated by data, further evaluation is directed at determining the extent of disease, including the size of the tumor and its attending mass effects. For patients who have progressed to heart failure—like ours—standard therapy is insufficient to control symptoms and prevent disease progression. To reduce morbidity and mortality, treatment must be directed at reducing the tumor volume and preventing tumor relapse. The most cost-effective and definitive treatment for a pituitary microadenoma is transsphenoidal resection. Subsequent radiotherapy may be required if the tumor cannot be completely excised. As tumor size and lateral extension increase, surgical debulking must be fortified by medical management.6Lugo G. Pena L. Cordido F. Clinical manifestations and diagnosis of acromegaly.Int J Endocrinol. 2012; 2012: 540398Crossref PubMed Scopus (77) Google Scholar Somatostatin analogs, dopamine agonists, or growth hormone receptor antagonists are prescribed to suppress elevated growth hormone (goal, <5 μg/L) and insulin-like growth factor-1 (goal, age-adjusted normal range). Cardiovascular risk factors should be addressed as well. Our patient's extreme clinical, radiographic, and echocardiographic abnormalities (Figure 1, Figure 2, Figure 3) represented typical findings in acromegalic cardiomyopathy. Physicians observing similar signs and symptoms in their patients should consider this potential diagnosis. Serological assessment for growth hormone and insulin-like growth factor-1, combined with magnetic resonance imaging of the brain, can confirm the diagnosis of acromegaly from a growth-hormone-secreting pituitary microadenoma. Transsphenoidal surgery was offered as first-line definitive therapy, as it has been reported to have the highest cure rates.7Biller B.M. Colao A. Petersenn S. Bonert V.S. Boscaro M. Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas.BMC Endocr Disord. 2010; 10: 10Crossref PubMed Scopus (45) Google Scholar Because the patient was initially reluctant to pursue surgery, medical therapy was implemented with diuretics, blood pressure and heart rate control, low-salt diet, and somatostatin analogs. Despite these measures, he continued to have New York Heart Association Class III heart failure symptoms. He then underwent transsphenoidal resection of the microadenoma. Over the next 2 years, his hormone levels normalized, his energy improved, and he had no further hospital admissions for heart failure. Our patient had numerous recurrent hospitalizations without a thorough evaluation until the underlying etiology was finally uncovered. His experience suggests a potential gap in the management of a high-risk group subject to a high mortality rate from cardiovascular complications. Vigilance for the characteristic presentation of acromegaly, application of confirmatory tests, and a multidisciplinary therapeutic approach can afford optimal management with reduction of morbidity and mortality in this severe disease.