An increased risk of cancer has been reported in patients treated with azathioprine. To assess the long-term risk of neoplasia in azathioprine-treated multiple sclerosis (MS) patients, we conducted a case-control study using the Lyon Multiple Sclerosis Database. From the 1,191 MS patients included in the database, we identified patients who developed cancer before December 31, 1991. Each case was then matched to three cancer-free MS controls by gender, date of birth, and date of MS onset. A matched analysis was performed to compare cases and controls for exposure to azathioprine therapy during the same follow-up period. Twenty-three MS patients with cancer were identified: 17 solid tumors, 2 skin carcinomas, 4 hematopoietic cancers. Cases had a mean age of 34.5 years +/- 10.2 (+/- SD) at clinical onset of MS and have been followed up for an average 13.8 years +/- 8.1 before being diagnosed with cancer. Fourteen cases (61%) and 34 controls (49%) had been treated with azathioprine for at least 1 month after being diagnosed with MS (adjusted odds ratio = 1.7; 95% confidence interval [CI], 0.6 to 4.6). When assessing risk associated with different durations of azathioprine therapy compared with no treatment at all, we found that MS patients had an increase in cancer risk of 1.3 (95% CI, 0.4 to 4.0) when treated less than 5 years, of 2.0 (95% CI, 0.4 to 9.1) when treated 5 to 10 years, and of 4.4 (95% CI 0.9 to 20.9) when treated more than 10 years. Similar results were obtained when assessing cancer risk associated with cumulative doses of azathioprine ever taken. This case-control study suggests that the overall long-term risk of cancer from azathioprine is low in MS patients. The results are suggestive of a dose-response relationship with no significant risk during the first years of treatment and a possible increased risk after about 10 years of continuous therapy. Further studies are needed to better assess the risk-benefit ratio of azathioprine in MS.

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The authors believe there is a prevalence of nonspecific headache in hypothyroidism and that it has a particular response to thyroid hormone therapy. Hypothyroidism is another cephalalgia with an endocrinological cause after menstrual cephalalgia. We suspect a metabolic or vascular pathophysiological process.