Hypothalamo–pituitary–adrenal axis, glucose metabolism and TNF-α in narcolepsy

Abstract

Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin, which regulates sleep and wakefulness and also influences appetite, neuroendocrine functions and metabolism. In this case-control study 11 patients with narcolepsy and cataplexy and 11 healthy adults underwent an oral glucose tolerance test and dexamethason-inhibition cortisol releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, the body mass index (BMI) 28.1 ± 6.6 and 25.5 ± 4.7. We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in narcolepsy patients. After hypothalamo-pituitary–adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethason suppression was significantly lower in narcoleptic patients suggesting a slight basal down-regulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following CRH stimulation, there were no significant differences in levels of ACTH or cortisol, and in adrenocortical responsivity to ACTH. Finally, narcoleptic patients displayed significantly higher plasma levels of TNF- α , solubleTNFR p55, soluble TNFR p75 and IL-6 after adjustment for BMI. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic HPA system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced. This study was supported by the grant of the Czech Ministry of Health NT 13238-4/2012, PRVOUK-P26/LF1/4 and by the European Union Framework 6 (MCRTN-CT-2004-512362).