The insulin tolerance test and the ovine corticotrophin-releasing hormone test in episodic cluster headache

Clinical observations indicate a central nervous system, probably hypothalamic, involvement in cluster headache pathogenesis. In order to investigate the supposed hypothalamic involvement in cluster headache, we followed the hypothalamic-pituitary-adrenal axis and autonomic responses to the insulin tolerance test and the ovine corticotrophin-releasing hormone test in episodic cluster headache patients, both during remission and during the cluster period. The study revealed increased basal cortisol levels in all cluster patients. A blunted cortisol response to ovine corticotrophin-releasing hormone, in spite of a normal ACTH surge, was subsequently found in both illness phases. These findings suggest hypothalamic-pituitary-adrenal axis hyperactivity in both cluster phases. Furthermore, reduced ACTH and cortisol responses after insulin challenge were also observed in both remission and cluster period patients; a reduced norepinephrine surge was seen only in the cluster period. Taken together, these results suggest a hypothalamic involvement in the altered neuroendocrinological and autonomic responses found in our patients.