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September 1989

Phenytoin-Induced Improvement in Muscle Cramping and Insulin Action in Three Patients With the Syndrome of Insulin Resistance, Acanthosis Nigricans, and Acral Hypertrophy

Author Affiliations

From the Charles A. Dana Research Institute, and the Harvard Thorndike Laboratory, Beth Israel Hospital, the Joint Department of Medicine, Beth Israel and Brigham and Women's Hospitals, Harvard Medical School (Drs Minaker, Flier, Landsberg, Young, Meneilly, and Rowe), the Geriatric Research Education Clinical Center (Drs Minaker, Rowe, and Meneilly), Brockton/West Roxbury Veterans Administration Medical Cen-; ter (Drs Minaker, Rowe, and Meneilly), Boston, Mass; and the Department of Neurology, University of Rochester (NY) School of Medicine and Dentistry (Drs Moxley and Kingston).

Arch Neurol. 1989;46(9):981-985. doi:10.1001/archneur.1989.00520450051018

• Phenytoin sodium has been used to treat muscle cramps of diverse causes, and is known to increase insulin sensitivity during long-term use. We have previously described a syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy with continual muscle cramping. The effect of 300 mg/d of phenytoin (Dilantin) on muscle cramping and carbohydrate economy was studied in three affected patients and four control subjects. Oral glucose tolerance tests, euglycemic insulin infusion studies, and monocyte insulin binding tests were conducted before and after phenytoin administration. All three patients had notable improvement in muscle cramps. In response to phenytoin, metabolic improvements were variable, with improvement characteristically better in patients with less severe baseline metabolic abnormalities. Patient 1, with the mildest degree of glucose intolerance, had decreased fasting insulin and blood glucose levels, improved glucose tolerance, and insulin-mediated glucose disposal, associated with an increase in monocyte insulin receptors. Patient 2 had reduced fasting plasma glucose and insulin levels and improved oral glucose tolerance, suggesting a beneficial effect on carbohydrate metabolism. Patient 3, with the most severely impaired carbohydrate economy, showed no metabolic improvement despite marked lessening of muscle pain. These clinical characteristics were unaffected in control subjects. We conclude that phenytoin is of value in the therapy of muscle cramps and glucose intolerance in patients with this syndrome.

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