LETTERS
Letters that report new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words; no more than five references and one figure or table can be used. See "Information for Authors" on page 1-6 for form of references. Manuscripts should include an abstract of length not exceeding 100 words. Letters will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten letters and to make changes that accord with our style. Myocardial Infarction in Men in the Third Decade of Life MYOCARDIAL INFARCTION
is uncommon
in the
fourth
decade and rare in the third decade of life. Our recent experience with several patients in the third decade of life led us to search for all patients 30 years of age or younger with this diagnosis seen in a large Veterans Administration hospital in the last 10 years, in order to characterize the nature of their disease. In a review of approximately 2500 male patients with documented acute myocardial infarction during this period, only eight were 30 years or younger. The clinical data from eight male patients, 21 to 30
years of age, are summarized in Table 1. Anterior infarction occurred in three patients, inferoposterior infarction in three, and subendocardial infarction in two. Acute myocardial infarction was confirmed by characteristic electrocardiographic and myocardial enzyme changes. Seven patients were cigarette smokers, three were hypertensive, and two had type IV hyperlipidemia. Three patients had a significant family history of myocardial infarction. Two patients (B, F ) , both with large transmural infarctions, had a history of remote drug abuse. In one patient (C), myocardial infarction was unsuspected in life but was found at autopsy with the typical intravascular findings of thrombotic thrombocytopenic purpura. One patient (E) had a tissue diagnosis of Buerger's disease after a below-knee amputation of his left leg after his acute infarction. In three of eight patients, serious ventricular ectopic activity complicated their early hospital course; ventricular fibrillation occurred in one patient. There was one instance of transient second-degree (Mobitz I) heart block. Five patients (A, B, F, G, H) underwent cardiac catheterization. Left ventricular dysfunction was documented in three patients (A, B, F) with elevated enddiastolic pressures and dyskinetic segments. The ejection fraction was depressed in two patients (B, F ) . Selective
Table 1 . Patient Summary*
Patient Age
A
yrs 26
B
25
C
21
D E
30 25
F
29
G
24
H
30
Location of Infarction
Anterior
Complications of Infarction
None
Conventional Risk Factors
Other Etiologic Considerations
Smoker f; positive None family history Ventricular tachycardia, Smoker f; Type IV None Anterior ventricular fibrilhyperlipidemia lation, second-degree A/V block (Mobitz I), congestive heart failure Inferoposterior None Thrombotic thromboHypertension t cytopenic purpura Subendocardial None None Serum sickness Ventricular Inferior Smoker f; positive Buerger's disease extrasystoles family history Ventricular extraSmoker f; hyper- None Anterior systoles, congestive tension % heart failure, subsequent subendocardial infarction Subendocardial None Smoker f; positive None family history Smoker f; hyper- None Inferior None tension J; type IV hyperlipidemia
(Cardiac Catheterization Coronary Arteriography
EDP
EF
mm 15
0.60
Normal
20
0.22
Normal
... ... 24
0.36
100% Lesion of LAD artery, 55% lesion of intermediate artery
8
0.63
Normal
8
0.58
100% Lesion of LCF artery, 90% lesion of diagonal branch of LAD artery
* t D P = left ventricular end-diastolic pressure; E F = ejection fraction; LAD = anterior descending branch of left coronary artery; LCF = circumflex branch of left coronary artery. t One pack of cigarettes per day or more. X Resting blood pressure greater than 140/90 mm Hg.
759
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coronary arteriography showed normal coronary arteries in three of the five patients (A, B, G ) . Of the seven who are alive, three are asymptomatic, and two (F, G) have exertional angina and positive stress tests. Two patients (B, F ) manifest chronic left ventricular failure, and the current status of one patient (D) is unknown. Although myocardial infarction and atherosclerotic coronary artery disease in the third decade of life are rare, they have been known to occur for a number of years, particularly in patients with anomalous coronary arteries, progeria, or a hypercholesterolemic genetic defect ( 1 ) . Coronary angiographic studies have shown myocardial infarction and typical angina pectoris to occur in patients with apparently normal, patent coronary arteries (2, 3 ) . That six of the eight patients with an otherwise typical myocardial infarction had either a rare, nonatherosclerotic cause or no demonstrable cause was a surprising finding. The patient with thrombotic thrombocytopenic purpura had no coronary atherosclerotic changes. The typical intravascular lesions of thrombotic thrombocytopenic purpura seen at necropsy have been associated with a high incidence of cardiac involvement including myocardial necrosis. The absence of typical symptoms and electrocardiographic findings were consistent with previous reports of myocardial infarction due to thrombotic thrombocytopenic purpura. The patient with serum sickness was one of the two survivors in whom we were not able to obtain coronary arteriograms preventing a definitive conclusion as to whether significant atherosclerotic coronary artery disease was present. Several features favor serum sickness as the sole cause: no previous or subsequent symptoms of ischemic heart disease; the temporal relation of his symptoms to other manifestations of serum sickness; and the apparent response to glucocorticoids. The heart may be a major target organ for the vasculitis secondary to deposition of circulating antigen-antibody complexes, although cardiac involvement has been a more prominent feature in the animal model than the sparsely recorded clinical experience ( 4 ) . The patient with Buerger's disease did not have diagnostic coronary arteriography. Although these patients usually have coronary atherosclerosis, sclerosis and thickening by hyalinized, calcified plaques may compromise the lumen and may well be an occasional cause of sudden death ( 2 ) . There were no identifiable causes for myocardial infarction in the three patients with angiographically normal coronary arteries. Coronary emboli or thrombi, spasm, or temporary occlusion by platelet aggregates with rapid resolution have been suggested as causes of infarction in similar instances ( 2 ) . Rare causes of myocardial infarction such as viral myocarditis, a toxic cardiomyopathy, or infarction associated with pregnancy or the administration of oral contraceptives are not relevant to these patients. Most of the recently recorded cases of myocardial infarction in the absence of significant coronary arterial occlusive disease have occurred in younger men ( 2 ) . The incidence of drug abuse and conventional risk factors in our patients is similar to other reports of young men with myocardial infarction (2, 5 ) . These remain unimpressive as causative factors in this group. The probability of a statistical bias against atherosclerotic coronary artery disease in our series may be responsible for its lower than expected incidence, because men with juvenile onset diabetes mellitus, severe hypertension, marked obesity, and clinical evidence of ischemic heart disease are excluded from the armed forces. 760
December
Extensive evaluation of the young male patient with myocardial infarction for a possible nonatherosclerotic cause for the infarction appears warranted. Such data should serve to further elucidate the prevalence, causes, and natural history of myocardial infarction in apparently healthy young men. This study was supported in part by grant #HL-05812 from the National Heart and Lung Institute and the Veterans Administration. J. V. NIXON, M.D. HAROLD R. LEWIS, M.D. THOMAS C. SMITHERMAN, M.D. WILLIAM SHAPIRO, M.D., F.A.C.P.
Cardiovascular Section Veterans Administration Hospital and University of Texas Health Science Center Dallas, TX 75216 Received 6 July 1976. REFERENCES
1. WENGER NK: Rare causes of coronary artery disease, in The Heart, 3rd ed., edited by HURST JW, LOGUE BR, SCHLANT RC, et
al, New York, McGraw-Hill Book Company, 1974, pp. 1154-1161 2. KHAN AF, HAYWOOD LJ: Myocardial infarction in nine patients with radiologically patent coronary arteries. N Engl J Med 291: 427-431, 1974 3. NEILL WA, JUDKINS MP, DHINDSA DS, et al: Clinically suspect
ischemic heart disease not corroborated by demonstrable coronary artery disease. Physiologic investigations and clinical course. Am J Cardiol 29:171-179, 1972 4. CATALANO TC: Myocardial infarction after serum sickness from tetanus anti-toxin. JAMA 188:1154-1156, 1964 5. DODLER MA, OLIVER MF: Myocardial infarction in young men. Study of risk factors in nine countries. Br Heart J 37:493-503, 1975
Magnesium-Induced Bradycardia DEPRESSION of sinoatrial and atrioventricular conduction due to severe hypermagnesemia (serum magnesium concentration, 10 to 15 meq/litre) has been previously well documented (1-3). We recently had the opportunity to observe a patient with chronic renal insufficiency who showed severe junctional bradycardia associated with mild hypermagnesemia (serum magnesium concentration, 3.3 to 4.8 meq/litre). We wish to emphasize the association between mild elevations in serum magnesium concentration and clinical cardiotoxicity. A 62-year-old woman was admitted to Colorado General Hospital for the evaluation of hematemesis and melena. Past medical history included diabetes mellitus since age 50, lumbosacral osteoarthritis, hypertension, and peripheral vascular disease. Her therapy consisted of a 1000 calorie American Diabetic Association diet, indomethacin, aspirin, reserpine, and sodium warfarin. She was not receiving digitalis. Initial physical examination showed a blood pressure of 110/70 mm Hg and pulse, 120/min without orthostatic change. Cardiac examination showed a 2/6 systolic ejection murmur at the aortic area. The remainder of the examination was unremarkable. Both nasogastric aspirate and stool were hematest-positive. Initial laboratory evaluation showed a hematocrit value of 36%; sodium, 138 meq/litre; potassium, 5.2 meq/litre; chloride, 105 meq/litre; and C0 2 content, 18 meq/litre. Blood urea nitrogen was 82 mg/dl; creatinine, 3.5 mg/dl; and creatinine clearance, 13 ml/min. The initial electrocardiogram showed a sinus tachycardia of 125 and nonspecific ST-T wave changes. Emergency endoscopy showed a prepyloric gastric ulcer without gastritis. The patient was begun on a magnesium-contain-
1976 • Annals of Internal Medicine • Volume 85 • N u m b e r 6
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19516/ by a University of California San Diego User on 06/26/2017
ing antacid (Maalox®) 30 ml/h. The patient responded well to conservative therapy and the hematocrit stabilized with 2 U of packed cells. On the seventh hospital day, a nurse recorded a pulse of 28/min. Blood pressure at that time was 104/60 mm Hg. An electrocardiogram done on that day showed a junctional bradycardia of 40 min and was otherwise unchanged from the admission tracing. At that time, the serum magnesium concentration was 4.5 meq/litre; potassium, 4.3 meq/litre; CO? content, 25 meq/litre; calcium, 9.0 mg/dl; and albumin, 3.6 g/ dl. Maalox® was withdrawn and the patient was begun on Amphojel® (aluminum hydroxide), 30 ml every 2 h. During the next 2 days, the rhythm reverted to normal sinus as the serum magnesium fell to 3.0 meq/litre (Figure 1). On the 11th hospital day, the patient was again placed on a magnesiumcontaining antacid every 2 h. On the 16th hospital day, junctional bradycardia redeveloped. At that time, the blood pressure was 160/80 mm Hg. The serum magnesium on that day was 4.8 meq/litre; potassium, 3.9 meq/litre; COL> content, 25 meq/litre; calcium, 8.8 mg/dl; and albumin, 3.6 g/dl. Once again magnesium-containing antacids were withdrawn and the patient was begun on Basaljel® (aluminum carbonate) every 4 h. As the serum magnesium fell to 3.0 meq/litre, the rhythm reverted to sinus at a rate of 90. An upper gastrointestinal series on the 25th hospital day was normal and the patient was discharged on the 28th hospital day. The manifestations of the cardiotoxicity associated with hypermagnesemia are generalized depression of conduction, bradyarrhythmias, and asystole ( 3 ) . These changes, however, are usually associated only with severe hypermagnesemia. Sinoatrial and atrioventricular block appear at levels above 10 meq/litre in conjunction with P-Q and QRS prolongation. At levels above 25 meq/litre, cardiac arrest in diastole occurs. It would appear that our patient developed junctional bradycardia in conjunction with mild hypermagnesemia. There was no concomitant administration of cardiodepressant drugs or evidence of acute myocardial ichemia
to explain the bradyarrythmia. When the patient was inadvertently rechallenged with magnesium-containing antacids, the junctional bradycardia reappeared. Junctional or sinus bradycardia has not been documented in this patient when the serum magnesium concentration has been below 3.0 meq/litre. The reason for the apparent sensitivity of our patient to mild hypermagnesemia is not clear. Randall and associates (4) have previously emphasized the observation that the serum magnesium concentrations at which cardiotoxicity appears in patients with renal insufficiency is considerably lower than in normal subjects. Patients with advanced renal insufficiency often manifest hypocalcemia, acidosis, and hyperkalemia and are often receiving digitalis, all of which may augment the cardiotoxicity of hypermagnesemia. These factors were not present in our patient. Additionally, there may be synergy between pre-existing junctional or His bundle disease and hypermagnesemia. It is known that the myocardium, particularly the intraventricular septum, concentrates magnesium to a greater extent than skeletal muscle ( 3 ) . Local myocardial magnesium concentration may be more critical to the genesis of cardiotoxicity than the systemic magnesium concentration. When evaluating any patient with bradycardia, hypermagnesemia should be considered, expecially when renal insufficiency is present. One need not require profound elevations in serum magnesium concentrations (10 to 20 meq/litre) before implicating hypermagnesemia as the cause of reversible junctional dysfunction. ARNOLD S. BERNS, M.D. K E N N E T H R. KOLLMEYER, PH.D.
Department of Medicine Division of Renal Diseases University of Colorado Medical Center 4200 East Ninth Avenue Denver, CO 80262 Received 17 May 1976. REFERENCES
1. SMITH
PK,
WINKLER
AW,
HOFF
HE:
Electrocardiographic
changes and concentrations of magnesium in serum following intravenous injection of magnesium salts. Am J Physiol 126:720730, 1939 2. WACKER WE, PARISI AF: Magnesium metabolism. N Engl J Med 278:712-717, 1968 3. HURST JW, LOGUE BR, SCHLANT RC, et al (eds.): The Heart.
3rd ed. New York, McGraw-Hill, 1974, pp. 1500-1502 4. RANDALL RE, COHEN MD, SPRAY CC JR, et al: Hypermagnesemia
in renal failure. Etiology and toxic manifestations. Ann Intern Med 61:73-88, 1964
Hashimoto's Thyroiditis, Myasthenia Gravis, Idiopathic Thrombocytopenic Purpura
Figure 1 . Heart rate and serum magnesium levels during administration and withdrawal of magnesium-containing antacid therapy.
HASHIMOTO'S THYROIDITIS has been associated with a various autoimmune disorders. The immunologic mechanisms involved in the pathogenesis of these disorders have not always been thought to be the same. Recently a case of Hashimoto's thyroiditis and autoimmune thrombocytopenic purpura was reported ( 1 ) , and it was suggested that a common mechanism may be involved in both diseases. Our observations in a patient with the above two conditions associated with myasthenia gravis, a disorder also suspected to be of autoimmune nature, gives further evidence that a common immunologic mechanism may be present. Letters
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19516/ by a University of California San Diego User on 06/26/2017
761
Table 1. Antibody Studies*
Antibody Tests Adrenal Gastric mucosa Thyroid agglutinating Thyroid microsomal Antithyroglobulin titer Antiplatelets Skeletal muscle Smooth muscle
Results
Normal Values
Negative + 2 Undiluted Positive 1:4 Negative 1:250 > 1:256 Positive + 4 undiluted Positive 1:4 Positive 1:250 Positive 1:16 000 1:32 Negative Negative
Negative Negative
Letters that report new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words; no more than five references and one figure or table can be used. See "Information for Authors" on page 1-6 for form of references. Manuscripts should include an abstract of length not exceeding 100 words. Letters will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten letters and to make changes that accord with our style. Myocardial Infarction in Men in the Third Decade of Life MYOCARDIAL INFARCTION
is uncommon
in the
fourth
decade and rare in the third decade of life. Our recent experience with several patients in the third decade of life led us to search for all patients 30 years of age or younger with this diagnosis seen in a large Veterans Administration hospital in the last 10 years, in order to characterize the nature of their disease. In a review of approximately 2500 male patients with documented acute myocardial infarction during this period, only eight were 30 years or younger. The clinical data from eight male patients, 21 to 30
years of age, are summarized in Table 1. Anterior infarction occurred in three patients, inferoposterior infarction in three, and subendocardial infarction in two. Acute myocardial infarction was confirmed by characteristic electrocardiographic and myocardial enzyme changes. Seven patients were cigarette smokers, three were hypertensive, and two had type IV hyperlipidemia. Three patients had a significant family history of myocardial infarction. Two patients (B, F ) , both with large transmural infarctions, had a history of remote drug abuse. In one patient (C), myocardial infarction was unsuspected in life but was found at autopsy with the typical intravascular findings of thrombotic thrombocytopenic purpura. One patient (E) had a tissue diagnosis of Buerger's disease after a below-knee amputation of his left leg after his acute infarction. In three of eight patients, serious ventricular ectopic activity complicated their early hospital course; ventricular fibrillation occurred in one patient. There was one instance of transient second-degree (Mobitz I) heart block. Five patients (A, B, F, G, H) underwent cardiac catheterization. Left ventricular dysfunction was documented in three patients (A, B, F) with elevated enddiastolic pressures and dyskinetic segments. The ejection fraction was depressed in two patients (B, F ) . Selective
Table 1 . Patient Summary*
Patient Age
A
yrs 26
B
25
C
21
D E
30 25
F
29
G
24
H
30
Location of Infarction
Anterior
Complications of Infarction
None
Conventional Risk Factors
Other Etiologic Considerations
Smoker f; positive None family history Ventricular tachycardia, Smoker f; Type IV None Anterior ventricular fibrilhyperlipidemia lation, second-degree A/V block (Mobitz I), congestive heart failure Inferoposterior None Thrombotic thromboHypertension t cytopenic purpura Subendocardial None None Serum sickness Ventricular Inferior Smoker f; positive Buerger's disease extrasystoles family history Ventricular extraSmoker f; hyper- None Anterior systoles, congestive tension % heart failure, subsequent subendocardial infarction Subendocardial None Smoker f; positive None family history Smoker f; hyper- None Inferior None tension J; type IV hyperlipidemia
(Cardiac Catheterization Coronary Arteriography
EDP
EF
mm 15
0.60
Normal
20
0.22
Normal
... ... 24
0.36
100% Lesion of LAD artery, 55% lesion of intermediate artery
8
0.63
Normal
8
0.58
100% Lesion of LCF artery, 90% lesion of diagonal branch of LAD artery
* t D P = left ventricular end-diastolic pressure; E F = ejection fraction; LAD = anterior descending branch of left coronary artery; LCF = circumflex branch of left coronary artery. t One pack of cigarettes per day or more. X Resting blood pressure greater than 140/90 mm Hg.
759
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coronary arteriography showed normal coronary arteries in three of the five patients (A, B, G ) . Of the seven who are alive, three are asymptomatic, and two (F, G) have exertional angina and positive stress tests. Two patients (B, F ) manifest chronic left ventricular failure, and the current status of one patient (D) is unknown. Although myocardial infarction and atherosclerotic coronary artery disease in the third decade of life are rare, they have been known to occur for a number of years, particularly in patients with anomalous coronary arteries, progeria, or a hypercholesterolemic genetic defect ( 1 ) . Coronary angiographic studies have shown myocardial infarction and typical angina pectoris to occur in patients with apparently normal, patent coronary arteries (2, 3 ) . That six of the eight patients with an otherwise typical myocardial infarction had either a rare, nonatherosclerotic cause or no demonstrable cause was a surprising finding. The patient with thrombotic thrombocytopenic purpura had no coronary atherosclerotic changes. The typical intravascular lesions of thrombotic thrombocytopenic purpura seen at necropsy have been associated with a high incidence of cardiac involvement including myocardial necrosis. The absence of typical symptoms and electrocardiographic findings were consistent with previous reports of myocardial infarction due to thrombotic thrombocytopenic purpura. The patient with serum sickness was one of the two survivors in whom we were not able to obtain coronary arteriograms preventing a definitive conclusion as to whether significant atherosclerotic coronary artery disease was present. Several features favor serum sickness as the sole cause: no previous or subsequent symptoms of ischemic heart disease; the temporal relation of his symptoms to other manifestations of serum sickness; and the apparent response to glucocorticoids. The heart may be a major target organ for the vasculitis secondary to deposition of circulating antigen-antibody complexes, although cardiac involvement has been a more prominent feature in the animal model than the sparsely recorded clinical experience ( 4 ) . The patient with Buerger's disease did not have diagnostic coronary arteriography. Although these patients usually have coronary atherosclerosis, sclerosis and thickening by hyalinized, calcified plaques may compromise the lumen and may well be an occasional cause of sudden death ( 2 ) . There were no identifiable causes for myocardial infarction in the three patients with angiographically normal coronary arteries. Coronary emboli or thrombi, spasm, or temporary occlusion by platelet aggregates with rapid resolution have been suggested as causes of infarction in similar instances ( 2 ) . Rare causes of myocardial infarction such as viral myocarditis, a toxic cardiomyopathy, or infarction associated with pregnancy or the administration of oral contraceptives are not relevant to these patients. Most of the recently recorded cases of myocardial infarction in the absence of significant coronary arterial occlusive disease have occurred in younger men ( 2 ) . The incidence of drug abuse and conventional risk factors in our patients is similar to other reports of young men with myocardial infarction (2, 5 ) . These remain unimpressive as causative factors in this group. The probability of a statistical bias against atherosclerotic coronary artery disease in our series may be responsible for its lower than expected incidence, because men with juvenile onset diabetes mellitus, severe hypertension, marked obesity, and clinical evidence of ischemic heart disease are excluded from the armed forces. 760
December
Extensive evaluation of the young male patient with myocardial infarction for a possible nonatherosclerotic cause for the infarction appears warranted. Such data should serve to further elucidate the prevalence, causes, and natural history of myocardial infarction in apparently healthy young men. This study was supported in part by grant #HL-05812 from the National Heart and Lung Institute and the Veterans Administration. J. V. NIXON, M.D. HAROLD R. LEWIS, M.D. THOMAS C. SMITHERMAN, M.D. WILLIAM SHAPIRO, M.D., F.A.C.P.
Cardiovascular Section Veterans Administration Hospital and University of Texas Health Science Center Dallas, TX 75216 Received 6 July 1976. REFERENCES
1. WENGER NK: Rare causes of coronary artery disease, in The Heart, 3rd ed., edited by HURST JW, LOGUE BR, SCHLANT RC, et
al, New York, McGraw-Hill Book Company, 1974, pp. 1154-1161 2. KHAN AF, HAYWOOD LJ: Myocardial infarction in nine patients with radiologically patent coronary arteries. N Engl J Med 291: 427-431, 1974 3. NEILL WA, JUDKINS MP, DHINDSA DS, et al: Clinically suspect
ischemic heart disease not corroborated by demonstrable coronary artery disease. Physiologic investigations and clinical course. Am J Cardiol 29:171-179, 1972 4. CATALANO TC: Myocardial infarction after serum sickness from tetanus anti-toxin. JAMA 188:1154-1156, 1964 5. DODLER MA, OLIVER MF: Myocardial infarction in young men. Study of risk factors in nine countries. Br Heart J 37:493-503, 1975
Magnesium-Induced Bradycardia DEPRESSION of sinoatrial and atrioventricular conduction due to severe hypermagnesemia (serum magnesium concentration, 10 to 15 meq/litre) has been previously well documented (1-3). We recently had the opportunity to observe a patient with chronic renal insufficiency who showed severe junctional bradycardia associated with mild hypermagnesemia (serum magnesium concentration, 3.3 to 4.8 meq/litre). We wish to emphasize the association between mild elevations in serum magnesium concentration and clinical cardiotoxicity. A 62-year-old woman was admitted to Colorado General Hospital for the evaluation of hematemesis and melena. Past medical history included diabetes mellitus since age 50, lumbosacral osteoarthritis, hypertension, and peripheral vascular disease. Her therapy consisted of a 1000 calorie American Diabetic Association diet, indomethacin, aspirin, reserpine, and sodium warfarin. She was not receiving digitalis. Initial physical examination showed a blood pressure of 110/70 mm Hg and pulse, 120/min without orthostatic change. Cardiac examination showed a 2/6 systolic ejection murmur at the aortic area. The remainder of the examination was unremarkable. Both nasogastric aspirate and stool were hematest-positive. Initial laboratory evaluation showed a hematocrit value of 36%; sodium, 138 meq/litre; potassium, 5.2 meq/litre; chloride, 105 meq/litre; and C0 2 content, 18 meq/litre. Blood urea nitrogen was 82 mg/dl; creatinine, 3.5 mg/dl; and creatinine clearance, 13 ml/min. The initial electrocardiogram showed a sinus tachycardia of 125 and nonspecific ST-T wave changes. Emergency endoscopy showed a prepyloric gastric ulcer without gastritis. The patient was begun on a magnesium-contain-
1976 • Annals of Internal Medicine • Volume 85 • N u m b e r 6
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19516/ by a University of California San Diego User on 06/26/2017
ing antacid (Maalox®) 30 ml/h. The patient responded well to conservative therapy and the hematocrit stabilized with 2 U of packed cells. On the seventh hospital day, a nurse recorded a pulse of 28/min. Blood pressure at that time was 104/60 mm Hg. An electrocardiogram done on that day showed a junctional bradycardia of 40 min and was otherwise unchanged from the admission tracing. At that time, the serum magnesium concentration was 4.5 meq/litre; potassium, 4.3 meq/litre; CO? content, 25 meq/litre; calcium, 9.0 mg/dl; and albumin, 3.6 g/ dl. Maalox® was withdrawn and the patient was begun on Amphojel® (aluminum hydroxide), 30 ml every 2 h. During the next 2 days, the rhythm reverted to normal sinus as the serum magnesium fell to 3.0 meq/litre (Figure 1). On the 11th hospital day, the patient was again placed on a magnesiumcontaining antacid every 2 h. On the 16th hospital day, junctional bradycardia redeveloped. At that time, the blood pressure was 160/80 mm Hg. The serum magnesium on that day was 4.8 meq/litre; potassium, 3.9 meq/litre; COL> content, 25 meq/litre; calcium, 8.8 mg/dl; and albumin, 3.6 g/dl. Once again magnesium-containing antacids were withdrawn and the patient was begun on Basaljel® (aluminum carbonate) every 4 h. As the serum magnesium fell to 3.0 meq/litre, the rhythm reverted to sinus at a rate of 90. An upper gastrointestinal series on the 25th hospital day was normal and the patient was discharged on the 28th hospital day. The manifestations of the cardiotoxicity associated with hypermagnesemia are generalized depression of conduction, bradyarrhythmias, and asystole ( 3 ) . These changes, however, are usually associated only with severe hypermagnesemia. Sinoatrial and atrioventricular block appear at levels above 10 meq/litre in conjunction with P-Q and QRS prolongation. At levels above 25 meq/litre, cardiac arrest in diastole occurs. It would appear that our patient developed junctional bradycardia in conjunction with mild hypermagnesemia. There was no concomitant administration of cardiodepressant drugs or evidence of acute myocardial ichemia
to explain the bradyarrythmia. When the patient was inadvertently rechallenged with magnesium-containing antacids, the junctional bradycardia reappeared. Junctional or sinus bradycardia has not been documented in this patient when the serum magnesium concentration has been below 3.0 meq/litre. The reason for the apparent sensitivity of our patient to mild hypermagnesemia is not clear. Randall and associates (4) have previously emphasized the observation that the serum magnesium concentrations at which cardiotoxicity appears in patients with renal insufficiency is considerably lower than in normal subjects. Patients with advanced renal insufficiency often manifest hypocalcemia, acidosis, and hyperkalemia and are often receiving digitalis, all of which may augment the cardiotoxicity of hypermagnesemia. These factors were not present in our patient. Additionally, there may be synergy between pre-existing junctional or His bundle disease and hypermagnesemia. It is known that the myocardium, particularly the intraventricular septum, concentrates magnesium to a greater extent than skeletal muscle ( 3 ) . Local myocardial magnesium concentration may be more critical to the genesis of cardiotoxicity than the systemic magnesium concentration. When evaluating any patient with bradycardia, hypermagnesemia should be considered, expecially when renal insufficiency is present. One need not require profound elevations in serum magnesium concentrations (10 to 20 meq/litre) before implicating hypermagnesemia as the cause of reversible junctional dysfunction. ARNOLD S. BERNS, M.D. K E N N E T H R. KOLLMEYER, PH.D.
Department of Medicine Division of Renal Diseases University of Colorado Medical Center 4200 East Ninth Avenue Denver, CO 80262 Received 17 May 1976. REFERENCES
1. SMITH
PK,
WINKLER
AW,
HOFF
HE:
Electrocardiographic
changes and concentrations of magnesium in serum following intravenous injection of magnesium salts. Am J Physiol 126:720730, 1939 2. WACKER WE, PARISI AF: Magnesium metabolism. N Engl J Med 278:712-717, 1968 3. HURST JW, LOGUE BR, SCHLANT RC, et al (eds.): The Heart.
3rd ed. New York, McGraw-Hill, 1974, pp. 1500-1502 4. RANDALL RE, COHEN MD, SPRAY CC JR, et al: Hypermagnesemia
in renal failure. Etiology and toxic manifestations. Ann Intern Med 61:73-88, 1964
Hashimoto's Thyroiditis, Myasthenia Gravis, Idiopathic Thrombocytopenic Purpura
Figure 1 . Heart rate and serum magnesium levels during administration and withdrawal of magnesium-containing antacid therapy.
HASHIMOTO'S THYROIDITIS has been associated with a various autoimmune disorders. The immunologic mechanisms involved in the pathogenesis of these disorders have not always been thought to be the same. Recently a case of Hashimoto's thyroiditis and autoimmune thrombocytopenic purpura was reported ( 1 ) , and it was suggested that a common mechanism may be involved in both diseases. Our observations in a patient with the above two conditions associated with myasthenia gravis, a disorder also suspected to be of autoimmune nature, gives further evidence that a common immunologic mechanism may be present. Letters
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19516/ by a University of California San Diego User on 06/26/2017
761
Table 1. Antibody Studies*
Antibody Tests Adrenal Gastric mucosa Thyroid agglutinating Thyroid microsomal Antithyroglobulin titer Antiplatelets Skeletal muscle Smooth muscle
Results
Normal Values
Negative + 2 Undiluted Positive 1:4 Negative 1:250 > 1:256 Positive + 4 undiluted Positive 1:4 Positive 1:250 Positive 1:16 000 1:32 Negative Negative
Negative Negative
