Myopathy

A 51-year-old woman was admitted to the intensive care unit for exacerbation of chronic obstructive pulmonary disease. She received antibiotics, neuromuscular blocking agents, and steroids. After 8 days in the intensive care unit, she was noted to be severely weak, her serum creatine kinase had risen to 1,692 U/L (normal, 20-220 U/L), and a muscle biopsy was consistent with critical illness myopathy. As a result of evaluating for resting tachycardia, the patient was found to be hyperthyroid. Her weakness rapidly improved within 1 month after treatment of her hyperthyroidism with iodine-131 and methimazole. The metabolic alterations associated with hyperthyroidism may enhance the risk of developing critical illness myopathy after the administration of antibiotics, neuromuscular blocking agents, and steroids in the intensive care unit

Introduction

Critical illness myopathy characteristically develops in the intensive care unit among patients who have been treated with multiple drugs, including neuromuscular-blocking agents, steroids, and antibiotics.12 An association between critical illness myopathy and hyperthyroidism has not been previously reported. We present a case report in which the metabolic alterations of hyperthyroidism may have enhanced the risk of developing critical illness myopathy.

Case Report

A 51-year-old woman was admitted to the intensive care unit with respiratory distress secondary to an exacerbation of chronic obstructive pulmonary disease. She was intubated. During her initial 8 days in the hospital intensive care unit, she was treated with succinylcholine chloride, midazolam hydrochloride, pancuronium bromide, ceftriaxone sodium, vancomycin hydrochloride, methylprednisolone sodium succinate, digoxin, and diltiazem hydrochloride. No definite evidence of sepsis or multiple organ failure occurred. After extubation and transfer from the intensive care unit on day 8, she was noted to be extremely weak. Her serum creatine kinase was noted to have risen from 188 to 1,692 U/L (normal, 20-220 U/L). On examination, she was plegic (grade 1 +) in her lower extremities and could barely move her upper extremities against gravity (grade 4-). Her deep tendon reflexes were absent throughout. Her sensory modalities were intact. A clinical diagnosis of critical illness myopathy was made. Electromyogram demonstrated diffuse small polyphasic motor unit potentials with a few fibrillations and increased firing rate for strength of contraction consistent with myopathy. Nerve conduction studies were normal. A left biceps muscle biopsy demonstrated atrophie type 2 myofibers that had amphophilic cytoplasm and mildly enlarged nuclei consistent with critical illness myopathy (Fig. 1). The atrophie myofibers had a gray-green color in sections stained by the modified trichrome technique and stained darkly with nonspecific esterase. Electron microscopy was not performed. Because of persistent tachycardia, thyroid function studies were obtained. Thyroid-stimulating hormone was less than 0.04 [mu]U/mL (normal, 0.45-3.90 [mu]U/mL), T4 was 15.9 [mu]g/dL (normal, 5.6-12.2 [mu]g/dL), and free thyroxine index was 21.1 [mu]g/dL (normal, 5.3-11.8 [mu]g/ dL). The patient was treated with iodine-131 and methimazole. Within 1 month of treatment of her hyperthyroidism, dramatic recovery of muscle strength had occurred. Muscle strength in the lower extremities was normal, and only a trace of proximal weakness in the upper extremities remained. Her deep tendon reflexes had also returned to normoactive.

Discussion

Although critical illness myopathy is being increasingly recognized, not all patients who are intubated in an intensive care unit or who have sepsis with or without multiple organ failure and who are also treated with neuromuscular-blocking agents, steroids, and/or antibiotics develop critical illness myopathy.3 Consequently, there must be additional risk factors that predispose certain patients to critical illness myopathy. This patient's case history suggests that hyperthyroidism may be one such additional risk factor for critical illness myopathy. Critical illness myopathy displays a preferential detrimental effect upon type 2 myofibers and myosin myofilaments.1 Thyroid hormone exerts a differential influence upon muscle fiber types and myosin myofilaments.4-11 Accordingly, the observation of critical illness myopathy in a hyperthyroid patient and associated dramatic and rapid recovery of muscle strength coincident with the treatment of hyperthyroidism suggests that the metabolic alterations associated with hyperthyrodism may influence the pathogenic metabolic mechanisms in critical illness myopathy. Because no treatment for critical illness myopathy is currently recognized, screening for hyperthyroidism in a clinically appropriate situation might be helpful because this patient had such a rapid recovery of muscle strength coincident with correction of her hyperthyroidism.

Finally, there are a couple of relevant points to emphasize. First, the clinical differentiation between hyperthyroid myopathy and critical illness myopathy is quite distinct. Hyperthyroid myopathy is typically associated with only mild objective muscle weakness, rare muscle atrophy, normal serum muscle enzymes, very rare presence of fibrillations on electromyography, and normal muscle biopsy by light microscopy.12 second, because thyroid hormone levels in the blood are frequently decreased in critically ill patients,13 the finding of elevated serum thyroid hormone levels, such as was demonstrated in this patient, has increased significance and reliability.

References

1. Hund E: Myopathy in critically ill patients. Crit Care Med 1999; 27: 2544-7.

2. Bolton CF: Critical illness polyneuropathy and myopathy. Crit Care Med 2001; 29: 2388-90.

3. de Letter MA, Schmilz PI, Visser LH, et al: Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 2001; 29: 2281-6.

4. Fitts RH, Brimmer CJ, Troup JP, Unsworth BR: Contractile and fatigue properties of thyrotoxic rat skeletal muscle. Muscle Nerve 1984; 7: 470-7.

5. Fremont P, Lazure C, Tremblay RR, Chrétien M, Rogers PA: Regulation of carbonic anhydrase III by thyroid hormone: opposite modulation in slow- and fasttwitch skeletal muscle. Biochem Cell Biol 1987; 65: 790-7.

6. Hagiwara M, Mamiya S, Hidaka H: Selective binding of L-throxine by myosin light chain kinase. J Biol Chem 1989; 264: 40-4.

7. Sayen MR, Rohrer DK, Dillmann WH: Thyroid hormone response of slow and fast Ca2+ ATPase mRNA in striated muscle. MoI Cell Endocrinol 1992; 87: 87-93.

8. Larsson L, Li X, Teresi A, Salviati G: Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats. J Physiol 1994; 481: 149-61.

9. Muller A, van der Linden GC, Zuidwijk MJ, Simonides WS, van der Laarse WJ, van Hardeveld C: Differential effects of thyroid hormone on the expression of sarcoplasmic reticulum Ca21-ATPase isoforms in rat skeletal muscle fibers. Biochem Biophys Res Commun 1994; 203: 1035-42.

10. Li X, Hughes SM, Salviati G, Teresi A, Larsson L: Thyroid hormone effects on contractility and myosin composition of soleus muscle and single fibres from young and old rats. J Physiol 1996; 494: 555-67.

11. Moriscot AS, Sayen MR, Hartong R, Wu P, Dillmann WH: Transcription of the rat sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene is increased by 3,5,3'-triiodothyronine receptor isoform-specific interactions with the myocytespecific enhancer factor-2a. Endocrinology 1997; 138: 26-32.

12. AlshekhleeA, Kaminski H J, Ruff RL: Neuromuscular manifestations of endocrine disorders. Neurol Clin 2002; 20: 35-58.

13. Stathatos N, Levetan C, Burman KD, Wartofsky L: The controversy of the treatment of critically ill patients with thyroid hormone. Best Pract Res Clin Endocrinol Metab 2001; 15: 465-78.

Guarantor: CAPT Jack E. Riggs, MC USNR

Contributors; Hemant K. Pandey, MD; CAPT Jack E. Riggs, MC USNR; Sydney S. Schochet Jr., MD

Department of Neurology, West Virginia University School of Medicine, Morgantown, WV.

The opinions and assertions herein are those of the authors and do not necessarily reflect those of the Navy Medical Department or the Department of Defense.

This manuscript was received for review in December 2002. The revised manuscript was accepted for publication in February 2003.

Reprint & Copyright © by Association of Military Surgeons of U.S., 2004.

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