Combined functional visual and hearing impairment in a population aged 75 and older in Finland and its influence on activities of daily living

To the Editor : We report a case of leuprolide-induced, noninflammatory myopathy. To our knowledge, this is the first such report. An 87-year-old man was self-referred for generalized weakness. He had been an avid, life-long walker, but over the preceding months had noticed increasing difficulty ambulating his daily several miles. Gradually, he was compelled to shorten his walks and developed trouble rising from a chair, pulling his pants on while standing, and brushing his hair. He denied dysphagia, ptosis, diplopia, pain, cramps, numbness, or fluctuations in his symptoms. When he complained to his physician about his insidiously progressive debility, he was told he was “just getting old.” The patient sought another opinion. A year before his evaluation by us, the patient had been diagnosed with prostate carcinoma and began treatment with the gonadotropin-releasing hormone agonist, leuprolide. He had been taking hydrochlorothiazide for several years for hypertension but was on no other prescription, alternative drugs, or over-the-counter medications. He was not a smoker, used alcohol moderately, and had no other health problems. He had no known family history of neuromuscular disease. He arrived for his appointment in a wheelchair. He had difficulty rising from a seating position without using his hands. He waddled slightly and had impaired toe-toheel walking. Manual motor testing confirmed moderately severe, symmetric, proximal limb and neck flexor weakness. Ocular motility, speech, sensation, myotatic reflexes, and muscle bulk were preserved, and the remainder of his physical examination was unremarkable. Laboratory investigations yielded normal results for the following: serum creatine kinase (CK), acetylcholine receptor and calcium channel antibodies, thyroid function tests, electrolytes, complete blood count, and urinalysis. Electromyography of left limb and paraspinal muscles verified a moderately severe, proximal myopathy, without evidence of fiber necrosis or vacuolar changes. A biopsy of the right deltoid revealed mild, nonspecific changes. A tentative diagnosis of an iatrogenic myopathy secondary to leuprolide was made, and, after obtaining agreement from the patient and his urologist, the leuprolide was discontinued. Over the next several months, the patient noted increasing improvement in his ability to ambulate, and, about 6 months after discontinuing the leuprolide, he was able to resume his several-mile, daily walk. Our follow-up physical and electromyographic examinations of the patient 9 months after he ceased taking leuprolide were normal. Drug-induced myopathies are common but likely underdiagnosed. 1,2 That medications such as corticosteroids and cholesterol-lowering agents may produce toxic myopathies is widely known, but there are many other agents less commonly responsible for iatrogenic myopathies, which may not be suspected. 1 An iatrogenic myopathy may or may not be associated with muscle fiber necrosis, so the serum CK level may not be elevated, and changes on muscle biopsy may be mild and nonspecific. 1 Clues of a toxic myopathy include absence of preexisting muscle dysfunction, gradual onset of muscular symptoms after the medication has been introduced, lack of other etiology for the myopathy, and complete or partial resolution of the muscular symptoms after the putative agent has been discontinued. 2 A particular drug may induce a variety of myopathies. 1 Thus, there is an isolated report of leuprolide inducing an inflammatory myopathy (CK 2,000 U/L) associated with changes on muscle biopsy compatible with polymyositis, which abated gradually after withdrawal of the leuprolide. 3 To our knowledge, no subsequent link between leuprolide and an iatrogenic myopathy has been published, 4 and ours is the first reported case of leuprolide inducing a noninflammatory myopathy. The mechanism for this is unknown, but the primary effect of leuprolide is to reduce testosterone production, 5 and testosterone deficiency has occasionally been associated with myopathy, 6 so this may have been the etiology of our patient’s myopathy. Whatever the mechanism, our patient’s course indicates that leuprolide may generate a myopathy, unassociated with an elevated CK, which could be overlooked. Clinicians caring for patients who develop gradual-onset, generalized weakness should consider the possibility of a toxic myopathy and consult lists of medications implicated as potentially myopathic. 1 Leuprolide should be added to such lists.