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Editorial note Understanding the acromegalic heart
International Journal of Cardiology, 2 (1983) 359-361 Elsevier Biomedical Press
Editorial
Understanding
359
Note
the acromegalic heart
Chronic hypersecretion of growth hormone directly or indirectly produces the metabolic, acral, and visceral abnormalities that characterize acromegaly. The word acromegaly is derived from the Greek words acre (end) and megas (large), indicating the enlargement of the hands and feet characteristic of: such patients. When untreated, acromegaly is associated with decreased life expectancy [ 1,221,in part due to cardiovascular and cerebrovascular diseases. An increased frequency of cardiovascular disorders is observed in acromegalic patients including .,cardiomegaly, systemic hypertension, premature coronary heart disease, arrhythmias, and congestive heart failure responding poorly to treatment. Acromegaly and ventricular hypertrophy More recently, asymmetric septal hypertrophy has been demonstrated by echocardiography in acromegalic patients by several groups [3-71 including the report by Csanady and coworkers [8] in this issue of the Jopal. These reports vary widely in the echocardiographic incidence of asymmetric septal hypertrophy, anterior mitral valve motion, concentric hypertrophy, left ventricular dilatation, and diminished left ventricular contractility. Asymmetric septal hypertrophy was originally reported to occur in 80% of a group of acromegalic patients [3], half of whom had anterior motion of the mitral valve. Subsequent reports have found asymmetric septal hypertrophy in 4-40s of patients, and anterior mitral valve motion is uncommon. In autopsy series of acromegaly, asymmetric septal hypertrophy is infrequently observed [9]. Concentric ventricular hypertrophy is the most common observation in most echocardiographic and autopsy series though the incidence ranges from 4 to 82%. Left ventricular dilatation and decreased ventricular function are uncommonly observed in contrast to the 24% incidence reported by Csanady and coworkers [8]. Regardless of its incidence, asymmetric septal hypertrophy had little clinical impact in most patients at the time of discovery. Different results These disparities in the reported incidence of echocardiographic findings undoubtedly reflect the particular interests of the referral center or investigator and the primary complaints of the patient. Most studies have been all inclusive, with measurements made in untreated, recently or incompletely treated, and cured patients. 0167-5273/83/0000-0000/%03.00
0 1983 Elsevier Biomedical
Press
360
There is no series of patients who have been evaluated before treatment and serially for a prolonged period thereafter. Such a study should ideally have a sizeable number of patients both inadequately treated and cured in order to assess the reversibility or progression of the cardiac abnormalities. This will be difficult to achieve because acromegaly is an uncommon disorder, and despite many advances in its treatment, the results remain woefully inadequate with cures often coming painfully slow if at all. Cardiac complications and level of growth hormone
What all studies to date have in common is a very poor correlation between the cardiovascular complications and the basal or glucose suppressed serum growth hormone level. Recent advances in our understanding of how growth hormone works may eventually reconcile this observation. Following its secretion, growth hormone stimulates the production of peptides by the liver called somatomedins A, B, and C. These peptides are carried in plasma bound to carrier proteins and are believed to mediate the effects of growth hormone on cartilage and skeletal tissues [lO,ll]. Their effects on other tissues such as heart are as yet unknown. Serum somatomedin-C levels, representing approximately one-third of the total somatomedin level in plasma, correlate much better with disease activity in acromegaly (heel pad thickness, fasting glucose, and one hour post-prandial glucose) than does glucose suppressed growth hormone levels, while fasting growth hormone levels show no correlation. Somatomedin-C generation appears to be loosely coupled to growth hormone levels, and patients with clinically active acromegaly and “normal” growth hormone levels may have elevated somatomedin-C levels [ 121.The emergence of these data undoubtedly will lead to changes in our definition of “cured” acromegaly and measurement of somatomedin-C levels in future studies may provide a clearer understanding of acromegalic heart disease. References 1 Wright AD, Hill DM, Lowy C, Fraser TR. Mortality in acromegaly. Q J Med 1970; 39: 1- 16. 2 Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol 1980; 12: 71-79. 2 Heame MJ, Sherber HS, DeLeon AC. Asymmetric septal hypertrophy in acromegaly: an echocardiographic study. Circulation 1975; 35 (Suppl II): 52. 4 Savage DD, Henry WL, Eastman RC, Borer JS, Gorden P. Echocardiographic assessment of cardiac anatomy and function in acromegalic patients. Am J Med 1979; 67: 823-829. 5 Smallridge RC, Rajfer S, Davia J, Schaaf M. Acromegaly and the heart. Am J Med 1979; 66: 22-27. 6 Mather HM, Boyd MJ, Jenkins JS. Heart size and function in acromegaly. Br Heart J 1979; 41: 697-701. 7 Nieminen MS, Elonen E, Pelkonen R, Frick MH. Acromegaly and the heart. Circulation 1978; 58: 757-763. 8 Csanady M, G&spar L, HSgye M, Gruber N. The heart in acromegaly: an echocardiographic study. Int J Cardiol 1983; 2: 349-357. 9 Lie JT, Grossman SJ. Pathology of the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J 1980; 100: 41-52.
361
10 Phillips LS, Vassilopoulou-Sellin R. Somatomedins. New Engl J Med 1980; 302: 371-380, 438-446. 11 Isaksson OGP, Jansson J, Gause IAM. Growth hormone stimulates longitudinal bone growth directly. Science 1982; 216: 1237-1239. 12 Clemmons DR. Van Wyk JJ, Ridgway EC, Kliman B, Kjellberg RN, Underwood LE. Evaluation of acromegaly by radioimmunoassay of somatomedin-C. New Engl J Med 1979; 301: 1138-l 142. Endocrine Section University of Pennsylvania 527 Johnson Pavilion G2 36th and Hamilton Walk Philadelphia, PA 19104, U.S.A.
Anthony S. Jennings
Editorial
Understanding
359
Note
the acromegalic heart
Chronic hypersecretion of growth hormone directly or indirectly produces the metabolic, acral, and visceral abnormalities that characterize acromegaly. The word acromegaly is derived from the Greek words acre (end) and megas (large), indicating the enlargement of the hands and feet characteristic of: such patients. When untreated, acromegaly is associated with decreased life expectancy [ 1,221,in part due to cardiovascular and cerebrovascular diseases. An increased frequency of cardiovascular disorders is observed in acromegalic patients including .,cardiomegaly, systemic hypertension, premature coronary heart disease, arrhythmias, and congestive heart failure responding poorly to treatment. Acromegaly and ventricular hypertrophy More recently, asymmetric septal hypertrophy has been demonstrated by echocardiography in acromegalic patients by several groups [3-71 including the report by Csanady and coworkers [8] in this issue of the Jopal. These reports vary widely in the echocardiographic incidence of asymmetric septal hypertrophy, anterior mitral valve motion, concentric hypertrophy, left ventricular dilatation, and diminished left ventricular contractility. Asymmetric septal hypertrophy was originally reported to occur in 80% of a group of acromegalic patients [3], half of whom had anterior motion of the mitral valve. Subsequent reports have found asymmetric septal hypertrophy in 4-40s of patients, and anterior mitral valve motion is uncommon. In autopsy series of acromegaly, asymmetric septal hypertrophy is infrequently observed [9]. Concentric ventricular hypertrophy is the most common observation in most echocardiographic and autopsy series though the incidence ranges from 4 to 82%. Left ventricular dilatation and decreased ventricular function are uncommonly observed in contrast to the 24% incidence reported by Csanady and coworkers [8]. Regardless of its incidence, asymmetric septal hypertrophy had little clinical impact in most patients at the time of discovery. Different results These disparities in the reported incidence of echocardiographic findings undoubtedly reflect the particular interests of the referral center or investigator and the primary complaints of the patient. Most studies have been all inclusive, with measurements made in untreated, recently or incompletely treated, and cured patients. 0167-5273/83/0000-0000/%03.00
0 1983 Elsevier Biomedical
Press
360
There is no series of patients who have been evaluated before treatment and serially for a prolonged period thereafter. Such a study should ideally have a sizeable number of patients both inadequately treated and cured in order to assess the reversibility or progression of the cardiac abnormalities. This will be difficult to achieve because acromegaly is an uncommon disorder, and despite many advances in its treatment, the results remain woefully inadequate with cures often coming painfully slow if at all. Cardiac complications and level of growth hormone
What all studies to date have in common is a very poor correlation between the cardiovascular complications and the basal or glucose suppressed serum growth hormone level. Recent advances in our understanding of how growth hormone works may eventually reconcile this observation. Following its secretion, growth hormone stimulates the production of peptides by the liver called somatomedins A, B, and C. These peptides are carried in plasma bound to carrier proteins and are believed to mediate the effects of growth hormone on cartilage and skeletal tissues [lO,ll]. Their effects on other tissues such as heart are as yet unknown. Serum somatomedin-C levels, representing approximately one-third of the total somatomedin level in plasma, correlate much better with disease activity in acromegaly (heel pad thickness, fasting glucose, and one hour post-prandial glucose) than does glucose suppressed growth hormone levels, while fasting growth hormone levels show no correlation. Somatomedin-C generation appears to be loosely coupled to growth hormone levels, and patients with clinically active acromegaly and “normal” growth hormone levels may have elevated somatomedin-C levels [ 121.The emergence of these data undoubtedly will lead to changes in our definition of “cured” acromegaly and measurement of somatomedin-C levels in future studies may provide a clearer understanding of acromegalic heart disease. References 1 Wright AD, Hill DM, Lowy C, Fraser TR. Mortality in acromegaly. Q J Med 1970; 39: 1- 16. 2 Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol 1980; 12: 71-79. 2 Heame MJ, Sherber HS, DeLeon AC. Asymmetric septal hypertrophy in acromegaly: an echocardiographic study. Circulation 1975; 35 (Suppl II): 52. 4 Savage DD, Henry WL, Eastman RC, Borer JS, Gorden P. Echocardiographic assessment of cardiac anatomy and function in acromegalic patients. Am J Med 1979; 67: 823-829. 5 Smallridge RC, Rajfer S, Davia J, Schaaf M. Acromegaly and the heart. Am J Med 1979; 66: 22-27. 6 Mather HM, Boyd MJ, Jenkins JS. Heart size and function in acromegaly. Br Heart J 1979; 41: 697-701. 7 Nieminen MS, Elonen E, Pelkonen R, Frick MH. Acromegaly and the heart. Circulation 1978; 58: 757-763. 8 Csanady M, G&spar L, HSgye M, Gruber N. The heart in acromegaly: an echocardiographic study. Int J Cardiol 1983; 2: 349-357. 9 Lie JT, Grossman SJ. Pathology of the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J 1980; 100: 41-52.
361
10 Phillips LS, Vassilopoulou-Sellin R. Somatomedins. New Engl J Med 1980; 302: 371-380, 438-446. 11 Isaksson OGP, Jansson J, Gause IAM. Growth hormone stimulates longitudinal bone growth directly. Science 1982; 216: 1237-1239. 12 Clemmons DR. Van Wyk JJ, Ridgway EC, Kliman B, Kjellberg RN, Underwood LE. Evaluation of acromegaly by radioimmunoassay of somatomedin-C. New Engl J Med 1979; 301: 1138-l 142. Endocrine Section University of Pennsylvania 527 Johnson Pavilion G2 36th and Hamilton Walk Philadelphia, PA 19104, U.S.A.
Anthony S. Jennings