Objectives-Chronic migraine (CM), previously called transformed migraine, is a frequent headache disorder that aVects 2%-3% of the general population. Analgesic overuse, insomnia, depression, and anxiety are disorders that are often comorbid with CM. Hypothalamic dysfunction has been implicated in its pathogenesis, but it has never been studied in patients with CM. The aim was to analyze hypothalamic involvement in CM by measurement of melatonin, prolactin, growth hormone, and cortisol nocturnal secretion. Methods-A total of 338 blood samples (13/patient) from 17 patients with CM and nine age and sex matched healthy volunteers were taken. Melatonin, prolactin, growth hormone, and cortisol concentrations were determined every hour for 12 hours. The presence of comorbid disorders was also evaluated. Results-An abnormal pattern of hypothalamic hormonal secretion was found in CM. This included: (1) a decreased nocturnal prolactin peak, (2) increased cortisol concentrations, (3) a delayed nocturnal melatonin peak in patients with CM, and (4) lower melatonin concentrations in patients with CM with insomnia. Growth hormone secretion did not diVer from controls. Conclusion-These results support hypothalamic involvement in CM, shown by a chronobiologic dysregulation, and a possible hyperdopaminergic state in patients with CM. Insomnia might be an important variable in the study findings. (J Neurol Neurosurg Psychiatry 2001;71:747-751)