The Insulin Tolerance Test and Ovine Corticotrophin-Releasing-Hormone Test in Episodic Cluster Headache II: Comparison With Low Back Pain Patients

Abstract

Hypothalamic involvement has been invoked to explain the periodicity of the cluster periods and rhythmicity of the pain attacks in cluster headache. To explore this hypothesis the ovine corticotrophin-releasing headaches sufferers during both cluster period and remission. A group of low back pain patients and healthy subjects comprised the control populations. For the o-CRH test, 7 healthy subjects, 7 low back pain patients, 6 cluster headache patients in remission, and 12 in cluster period were studied. Five healthy subjects, 7 low back pain patients, 6 cluster headache patients in remission, and 9 cluster period were administered the insulin tolerance test. Significantly increased basal cortisol levels were found in cluster headache patients in both illness phases (p < 0.0001), but not in low back pain patients. Significantly reduced cortisol response to the o-CRH test was observed in cluster headache patients in both phases compared to healthy controls (p < 0.02). A blunted ACTH and cortisol response (p < 0.0001 and p < 0.003 respectively) to the insulin tolerance test was present in cluster headache patients in both phases of the illness compared to healthy subjects and low back pain patients. On the contrary, the ACTH surge after insulin induced hypoglycemia was significantly increased in the low back pain patient group (p = 0.02). These results suggest that the altered hypothalamic-pituitary-adrenal axis responsiveness in cluster headache patients is not a consequence of the pain, and point to a central, probably hypothalamic derangement in this pathology.

Steroid hormones in cluster headaches

“…This result suggested hypothalamic-pituitary-adrenal axis hyperactivity and/or downregulation of adrenal corticotrophic cells during active cluster periods. The same findings were not realized in patients with low back pain, indicating the inadequate adrenal response to provocation was unrelated to pain and associated stress [35]. Concomitant elevated basal cortisol rates in episodic cluster headache subjects confirmed the suspicion of a hyperactive hypothalamic pituitary adrenal axis [35].…”

“…The same findings were not realized in patients with low back pain, indicating the inadequate adrenal response to provocation was unrelated to pain and associated stress [35]. Concomitant elevated basal cortisol rates in episodic cluster headache subjects confirmed the suspicion of a hyperactive hypothalamic pituitary adrenal axis [35]. Dexamethasone suppression tests in patients with episodic cluster headache during a cluster period or remission have demonstrated normal suppression, despite the previously mentioned elevated basal cortisol levels [36].…”

Nocturnal Secretion of Growth Hormone, Noradrenaline, Cortisol and Insulin in Cluster Headache Remission

“…There are no previous studies of insulin levels in CH and in the present study we could find no indications of disturbed insulin regulation in CH remission. However, it is possible that insulin‐related mechanisms are involved in CH pathophysiology, since it has been reported that eight of nine patients in active cluster period developed a typical CH attack during an insulin tolerance test (6). The patients had typical autonomic signs of hypoglycaemia before the attack and vasodilation due to hypoglycaemia was discussed as an underlying mechanism.…”

Hypoglycemia Rebound Migraine

“…For instance, patients with migraine (and by extension persons with diabetes) may have an enhanced sensitivity to endogenous insulin with a slow hypoglycemic recovery phase, even in the presence of a normal hypothalamic‐pituitary‐adrenal axis. Patients with cluster headache may also exhibit blunted ACTH and cortisol responses to the insulin tolerance test 12,13 . A traditionally held view is that plasma free fatty acid concentrations are increased in migrainous patients following a period of fasting.…”