Acta med. scand. Vol. 198, pp. 137-139, 1975
Hypothyroidism with Subacute Pseudomyotonia an Early Form of Hoffmann’s Syndrome?
-
Report of a Case
Jean Cronstedt, Lasse Carling and Henrik Ostberg From the Department of Internal Medicine, Avesta Hospital, Avesta, Sweden
ABSTRACT. A 25-year-old man was admitted to the hospital because of painful muscle cramps and action myospasms of subacute onset and of 6 weeks’ duration. No myotonia could be demonstrated objectively and his deep tendon reflexes showed no prolongation of the relaxation phase. Serum creatinine was raised but creatinine clearance was normal. Serum levels of aldolase, CPK, ASAT and ALAT were increased but ordinary light microscopy revealed no histological signs of muscle disease in a quadriceps biopsy. ECG showed a prolonged PQ interval and flat T waves in the left precordial leads. Laboratory tests of thyroid function revealed intensive hypothyroidism, and high titers of circulating thyroid antibodies were demonstrated. During 21/2 months of thyroid therapy, the muscle symptoms gradually disappeared completely and the patient could return to work. By that time the serum enzymes and the ECG had normalized. Despite the lack of objective signs of myotonia, we consider that the very dominant subjective muscle symptoms, severe enough to prevent the patient from performing his ordinary manual work and completely reversible on thyroid therapy, justify the designation of hypothyroid myopathy. The question is raised whether the case represents an early form of Hoffmann’s syndrome.
Hypothyroidism is often accompanied by mild muscle symptoms such as increased volume, stiffness, slowness of contraction and slowness of tendon reflexes. In rare cases, marked muscle symptoms may be present. The clinical picture may then simulate congenital myotonia or myotonic dystrophy. Cretinism manifesting such a muscle picture is called Debre-Semelaigne syndrome and Reprint requests to: Dr J . Cronstedt, Bollnas Sjukhus, S-82101 Bollnas, Sweden.
similar muscle symptoms accompanying myxedema are designated Hoffmann’s syndrome (6). The present paper describes the clinical and laboratory findings in a young man with severe hypothyroidism, presenting clinically with subacute pseudomyotonia. CASE REPORT A 25-year-old man was admitted to the hospital on Sept. 2, 1974 because of painful muscle cramps and action myospasms of approximately 6 weeks’ duration. Up to a few weeks before the onset of these muscle symptoms, he had been playing football without difficulty. The cramps and myospasms had occurred with increasing frequency and severity in the arms, the legs, the chest, and the abdomen, predominantly with movement. Finally the patient had to stop doing his ordinary manual work and consulted a general pntctitioner, who referred him to our hospital with the diagnosis of suspected dystrophia myotonica. On physical examination his voice was deep, his face somewhat expressionless, and his skin dry. He had no goiter and the thyroid was not tender. The BP was 130/95. The deep tendon reflexes were normal. No prolongation of the relaxation phase could be demonstrated. Objectively, no myotonia could be demonstrated but the patient complained of a feeling of stiffness when stretching his fingers after firm closure of the fists. Laboratory investigations yielded following results: ESR 4 mm/h, H b 16.0 g/lOO ml, hematocrit 44%. leucocytes 8100/mm3. Potassium 3.65, sodium 139.5 and calcium 4.6 mEq/l. Creatinine range 1.6-1.9 mglla0 ml. There was no proteinuria and the sediment was normal. Creatinine clearance was 96.4 ml/min. Bilirubin was 0.62 mg/lOO ml, alkaline phosphatase 31 mU/ml(20-48), ASAT range 59-70 (below 40). ALAT 68-48 (below 40) and LD 430-504 U/l (below 475). Cholesterol was 350 mg/lOO ml, triglycerides 2.15 mmol/l and lipoprotein electrophoresis showed increased P-lipoprotein. Plasma protein analysis was normal. Creatinine phosphokinase (CPK) was 564 IU/l (0-100) Acta rned. scand. 198
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and aldolase 4.2 mU/ml (0.5-3.1). T,-iodine was 0.3 pg/IOO ml (2.4-6.0), T,-sephadex test 70% (80-120) and TSH more than 50 mU/I (1.5-7.2). Antibodies were demonstrated in a titer of 1/400 against thyroglobulin and in a titer of more than I/IW against cytoplasmic thyroid antigen. ANF test was negative. Light microscopy of a quadriceps biopsy revealed no histological signs of muscle disease. Liver biopsy showed minimal fatty change. ECG showed a PQ interval of 0.26 sec and flat T waves in the left precordial leads at a heart rate of 65/min. X-ray of the chest was normal. The size of the cardiac silhouette was 910 ml, corresponding to 410 ml/m2 BSA. The diagnosis of suspected Hoffmann’s syndrome was made and treatment with levothyroxine was started. The muscle symptoms gradually disappeared. After two months’ therapy the daily dose of levothyroxine had been raised to 0.3 mg and the T,-1 was 5 . 2 @g/lOO ml. One month later the following values of serum enzymes were obtained: CPK 70, ASAT 23, ALAT 22 U/I. A new ECG showed that the PQ interval had been reduced to 0.18 sec and that the T wave changes in the left precordial leads had disappeared a t a heart rate of 55/min. By that time the pseudomyotonic symptoms had completely vanished and the patient could return to work. Since then he has been able to perform his ordinary manual work regularly for an observation period of two months without any recurrence of muscle symptoms. The levothyroxine dose has been retained at 0.3 mg daily.
DISCUSSION A patient is described in whom intensive hypothyroidism presented clinically with pseudomyotonia of subacute onset and of such severity that he had to stop doing his ordinary manual work. Subjectively the patient experienced painful muscle cramps and action myospasms. Yet no myotonia could be demonstrated objectively and the deep tendon reflexes showed no prolongation of the relaxation phase. The very low level of T,-I and the very high level of TSH indicate a severe degree of primary hypothyroidism. The high levels of circulating thyroid antibodies point to an autoimmune thyroiditis as the cause of the myxedema. The high level of CPK and the increased levels of aldolase, ASAT and ALAT indicate muscle disorder, but ordinary light microscopy of the muscle biopsy revealed no histological signs of muscle disease. Increased serum concentrations of CPK, ASAT and LD are frequently seen in hypothyroidism (4) and thus do not as such differentiate our case from ordinary cases of hypothyroidism. Theoretically, the liver involvement as shown by the minimal fatty change demonstrated in the liver biopsy, could also have Acta med. scnnd. 198
contributed to the raised levels of ASAT, ALAT and LD in our case. All other liver function tests were normal, however. The important differentiating aspect of our case is the manner in which the hypothyroidism presented clinically. The muscle symptoms developed over a short period and became severe enough to prevent the patient from performing his ordinary manual work. The painful muscle cramps and action myospasms were the only subjective complaints, leading the diagnostic thinking of all doctors involved in the direction of a subacute muscle disease. Although many patients with hypothyroidism complain of stiff, aching muscles (4), we have never encountered any previous patient with such completely dominant muscle symptoms. The absence of histological signs of other muscle disease and the complete clinical and laboratory restitution on thyroid therapy do strongly support the diagnosis of hypothyroid myopathy. Reports in the literature of cases of myxedema myopathy are rare. Salick et al. (5) and Ahuja ( I ) reported one case each. Both patients had experienced muscle symptoms for several years prior to diagnosis and treatment. In both, muscle biopsies revealed increased numbers of sarcolemmal nuclei. In the case of Salick et al., occasional necrotic fibers were also found and in that of Ahuja, abundant amorphous substance was reported. In contrast to these two cases, our patient had experienced muscle symptoms for some 6 weeks only prior to the muscle biopsy. Whether this difference in duration of hypothyroidism can account for the fact that histological signs of muscle disease were lacking in our case, remains to be established. Fessel (3) reported three hypothyroid patients who presented with muscle symptoms. In two of them, however, no improvement of muscle function was seen on thyroid treatment, and in the third, improvement was seen only after adrenal steroids had been added to the regimen. It seems questionable, therefore, whether hypothyroidism was really the cause of the muscle symptoms in these three cases. In 1969, Bondy (2) reported that he had only seen one patient who probably had myxedema myopathy. He concluded that true hypothyroid rnyopathy must be a very rare complication of myxedema. In our opinion, the case presented by u s represents such a very rare manifestation of hypothyroidism. We would like to suggest that our pa-
Hoffmann’s syndrome
tient suffered from an early form of Hoffmann’s syndrome. The pathogenetic mechanisms of muscle dysfunction in such cases remains to be established.
139
3. Fessel, W. J.: Ann. rheum. Dis. 27: 590, 1968. 4. Ingbar, s. H . Lk Woeber, K.: In: Harrison’s principles of internal medicine (ed. M. M. Wintrobe, G. W. R. D, E, Braunwald, K , lsselbacher and R. G . Petersdorf), p. 474. McCraw-Hill, New York 1974. 5. Salick, A. I.. Colachis, S. C. & Pearson, C. M.: Arch. phys. Med. 49:230, 1968. 6. Tyler, F. H . & Adarns, R . D.: In: Harrison’s principles of internal medicine, p. 1925. McCraw-Hill, New York 1974. J ,
REFERENCES 1. Ahuja, M. M. S.: Indian J. med. Sci. 20: 537, 1966.
2. Bondy, P. K.: in: Year book of medicine (ed. D. E. Rogers, C. Muschenheim, U. B. Castle, T. J. Reeves, F. J. Ingelfinger, P. K. Bondy and F. H. Epstein), p. 710. Year Book Medical Publishers, Chicago 1969.
Acta med. scund. 198
Hypothyroidism with Subacute Pseudomyotonia an Early Form of Hoffmann’s Syndrome?
-
Report of a Case
Jean Cronstedt, Lasse Carling and Henrik Ostberg From the Department of Internal Medicine, Avesta Hospital, Avesta, Sweden
ABSTRACT. A 25-year-old man was admitted to the hospital because of painful muscle cramps and action myospasms of subacute onset and of 6 weeks’ duration. No myotonia could be demonstrated objectively and his deep tendon reflexes showed no prolongation of the relaxation phase. Serum creatinine was raised but creatinine clearance was normal. Serum levels of aldolase, CPK, ASAT and ALAT were increased but ordinary light microscopy revealed no histological signs of muscle disease in a quadriceps biopsy. ECG showed a prolonged PQ interval and flat T waves in the left precordial leads. Laboratory tests of thyroid function revealed intensive hypothyroidism, and high titers of circulating thyroid antibodies were demonstrated. During 21/2 months of thyroid therapy, the muscle symptoms gradually disappeared completely and the patient could return to work. By that time the serum enzymes and the ECG had normalized. Despite the lack of objective signs of myotonia, we consider that the very dominant subjective muscle symptoms, severe enough to prevent the patient from performing his ordinary manual work and completely reversible on thyroid therapy, justify the designation of hypothyroid myopathy. The question is raised whether the case represents an early form of Hoffmann’s syndrome.
Hypothyroidism is often accompanied by mild muscle symptoms such as increased volume, stiffness, slowness of contraction and slowness of tendon reflexes. In rare cases, marked muscle symptoms may be present. The clinical picture may then simulate congenital myotonia or myotonic dystrophy. Cretinism manifesting such a muscle picture is called Debre-Semelaigne syndrome and Reprint requests to: Dr J . Cronstedt, Bollnas Sjukhus, S-82101 Bollnas, Sweden.
similar muscle symptoms accompanying myxedema are designated Hoffmann’s syndrome (6). The present paper describes the clinical and laboratory findings in a young man with severe hypothyroidism, presenting clinically with subacute pseudomyotonia. CASE REPORT A 25-year-old man was admitted to the hospital on Sept. 2, 1974 because of painful muscle cramps and action myospasms of approximately 6 weeks’ duration. Up to a few weeks before the onset of these muscle symptoms, he had been playing football without difficulty. The cramps and myospasms had occurred with increasing frequency and severity in the arms, the legs, the chest, and the abdomen, predominantly with movement. Finally the patient had to stop doing his ordinary manual work and consulted a general pntctitioner, who referred him to our hospital with the diagnosis of suspected dystrophia myotonica. On physical examination his voice was deep, his face somewhat expressionless, and his skin dry. He had no goiter and the thyroid was not tender. The BP was 130/95. The deep tendon reflexes were normal. No prolongation of the relaxation phase could be demonstrated. Objectively, no myotonia could be demonstrated but the patient complained of a feeling of stiffness when stretching his fingers after firm closure of the fists. Laboratory investigations yielded following results: ESR 4 mm/h, H b 16.0 g/lOO ml, hematocrit 44%. leucocytes 8100/mm3. Potassium 3.65, sodium 139.5 and calcium 4.6 mEq/l. Creatinine range 1.6-1.9 mglla0 ml. There was no proteinuria and the sediment was normal. Creatinine clearance was 96.4 ml/min. Bilirubin was 0.62 mg/lOO ml, alkaline phosphatase 31 mU/ml(20-48), ASAT range 59-70 (below 40). ALAT 68-48 (below 40) and LD 430-504 U/l (below 475). Cholesterol was 350 mg/lOO ml, triglycerides 2.15 mmol/l and lipoprotein electrophoresis showed increased P-lipoprotein. Plasma protein analysis was normal. Creatinine phosphokinase (CPK) was 564 IU/l (0-100) Acta rned. scand. 198
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and aldolase 4.2 mU/ml (0.5-3.1). T,-iodine was 0.3 pg/IOO ml (2.4-6.0), T,-sephadex test 70% (80-120) and TSH more than 50 mU/I (1.5-7.2). Antibodies were demonstrated in a titer of 1/400 against thyroglobulin and in a titer of more than I/IW against cytoplasmic thyroid antigen. ANF test was negative. Light microscopy of a quadriceps biopsy revealed no histological signs of muscle disease. Liver biopsy showed minimal fatty change. ECG showed a PQ interval of 0.26 sec and flat T waves in the left precordial leads at a heart rate of 65/min. X-ray of the chest was normal. The size of the cardiac silhouette was 910 ml, corresponding to 410 ml/m2 BSA. The diagnosis of suspected Hoffmann’s syndrome was made and treatment with levothyroxine was started. The muscle symptoms gradually disappeared. After two months’ therapy the daily dose of levothyroxine had been raised to 0.3 mg and the T,-1 was 5 . 2 @g/lOO ml. One month later the following values of serum enzymes were obtained: CPK 70, ASAT 23, ALAT 22 U/I. A new ECG showed that the PQ interval had been reduced to 0.18 sec and that the T wave changes in the left precordial leads had disappeared a t a heart rate of 55/min. By that time the pseudomyotonic symptoms had completely vanished and the patient could return to work. Since then he has been able to perform his ordinary manual work regularly for an observation period of two months without any recurrence of muscle symptoms. The levothyroxine dose has been retained at 0.3 mg daily.
DISCUSSION A patient is described in whom intensive hypothyroidism presented clinically with pseudomyotonia of subacute onset and of such severity that he had to stop doing his ordinary manual work. Subjectively the patient experienced painful muscle cramps and action myospasms. Yet no myotonia could be demonstrated objectively and the deep tendon reflexes showed no prolongation of the relaxation phase. The very low level of T,-I and the very high level of TSH indicate a severe degree of primary hypothyroidism. The high levels of circulating thyroid antibodies point to an autoimmune thyroiditis as the cause of the myxedema. The high level of CPK and the increased levels of aldolase, ASAT and ALAT indicate muscle disorder, but ordinary light microscopy of the muscle biopsy revealed no histological signs of muscle disease. Increased serum concentrations of CPK, ASAT and LD are frequently seen in hypothyroidism (4) and thus do not as such differentiate our case from ordinary cases of hypothyroidism. Theoretically, the liver involvement as shown by the minimal fatty change demonstrated in the liver biopsy, could also have Acta med. scnnd. 198
contributed to the raised levels of ASAT, ALAT and LD in our case. All other liver function tests were normal, however. The important differentiating aspect of our case is the manner in which the hypothyroidism presented clinically. The muscle symptoms developed over a short period and became severe enough to prevent the patient from performing his ordinary manual work. The painful muscle cramps and action myospasms were the only subjective complaints, leading the diagnostic thinking of all doctors involved in the direction of a subacute muscle disease. Although many patients with hypothyroidism complain of stiff, aching muscles (4), we have never encountered any previous patient with such completely dominant muscle symptoms. The absence of histological signs of other muscle disease and the complete clinical and laboratory restitution on thyroid therapy do strongly support the diagnosis of hypothyroid myopathy. Reports in the literature of cases of myxedema myopathy are rare. Salick et al. (5) and Ahuja ( I ) reported one case each. Both patients had experienced muscle symptoms for several years prior to diagnosis and treatment. In both, muscle biopsies revealed increased numbers of sarcolemmal nuclei. In the case of Salick et al., occasional necrotic fibers were also found and in that of Ahuja, abundant amorphous substance was reported. In contrast to these two cases, our patient had experienced muscle symptoms for some 6 weeks only prior to the muscle biopsy. Whether this difference in duration of hypothyroidism can account for the fact that histological signs of muscle disease were lacking in our case, remains to be established. Fessel (3) reported three hypothyroid patients who presented with muscle symptoms. In two of them, however, no improvement of muscle function was seen on thyroid treatment, and in the third, improvement was seen only after adrenal steroids had been added to the regimen. It seems questionable, therefore, whether hypothyroidism was really the cause of the muscle symptoms in these three cases. In 1969, Bondy (2) reported that he had only seen one patient who probably had myxedema myopathy. He concluded that true hypothyroid rnyopathy must be a very rare complication of myxedema. In our opinion, the case presented by u s represents such a very rare manifestation of hypothyroidism. We would like to suggest that our pa-
Hoffmann’s syndrome
tient suffered from an early form of Hoffmann’s syndrome. The pathogenetic mechanisms of muscle dysfunction in such cases remains to be established.
139
3. Fessel, W. J.: Ann. rheum. Dis. 27: 590, 1968. 4. Ingbar, s. H . Lk Woeber, K.: In: Harrison’s principles of internal medicine (ed. M. M. Wintrobe, G. W. R. D, E, Braunwald, K , lsselbacher and R. G . Petersdorf), p. 474. McCraw-Hill, New York 1974. 5. Salick, A. I.. Colachis, S. C. & Pearson, C. M.: Arch. phys. Med. 49:230, 1968. 6. Tyler, F. H . & Adarns, R . D.: In: Harrison’s principles of internal medicine, p. 1925. McCraw-Hill, New York 1974. J ,
REFERENCES 1. Ahuja, M. M. S.: Indian J. med. Sci. 20: 537, 1966.
2. Bondy, P. K.: in: Year book of medicine (ed. D. E. Rogers, C. Muschenheim, U. B. Castle, T. J. Reeves, F. J. Ingelfinger, P. K. Bondy and F. H. Epstein), p. 710. Year Book Medical Publishers, Chicago 1969.
Acta med. scund. 198
