Endocrine function in multiple sclerosis.

Increased Number of Corticotropin-Releasing Hormone Expressing Neurons in the Hypothalamic Paraventricular Nucleus of Patients with Multiple Sclerosis

“…However, such a possibility does not agree with the increased levels of corticosteroids reported in MS patients [6]. The increase of HPA axis activity may influence the course of an autoimmune disease.…”

“…Indeed, patients with rheumatoid arthritis have a defective HPA axis response based upon a hypothalamic defect [22], On the other hand, KJapps et al [4] did not find decreased basal levels of adrenal or pitu itary hormones in MS patients. However, the poststimu latory secretion of cortisol was impaired in 4 of 26 patients which suggests a preclinical endocrine insuffi ciency in some of them [23], However, other studies reported increased corticosteroid levels in MS patients [6] which was to be expected on the basis of the increased activity of the HPA axis, as judged from the observed increased number of CRH neurons in MS patients ( fig. 3).…”

“…This nucleus is of particular interest in MS, since it contains the corti cotropin-releasing hormone (CRH) neurons that regulate the levels of pituitary adrenocorticotropic hormone and thus adrenal cortisol. Recent observations in experimen tal allergic encephalomyelitis (EAE), an animal experi mental model for MS, indicate that the activity of the hypothalamo-pituitary-adrenal (HPA) system might re veal information on individual differences in susceptibili ty for and recovery from MS. Lower corticosteroid levels were accompanied by a higher susceptibility of rat strains to EAE, and elevated corticosteroid levels are necessary for spontaneous recovery of rat strains from EAE [5], An increased HPA axis activity has indeed been reported in MS on the basis of the peripheral corticosteroid levels [6]. Therefore, it was thought to be of interest to determine in the present study the number of CRH-immunoreactive (CRH-IR) neurons in the PVN as a measure for the activi ty of this system [7,8], In addition, the number of argi nine vasopressin (AVP) immunoreactive (AVP-IR) neu rons was determined as a second population of neurons with potential corticotropin-releasing activity [7], More over, the number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since this is a source of central innervation of the autonomic brain stem [9].…”

Hypothalamic-pituitary-adrenal axis function and cytokine production in multiple sclerosis with or without interferon-β treatment

“…Previous investigations on the HPA axis activity in MS provided conflicting results. While earlier studies showed normal function (23, 24), recent reports have pointed out mild activation of this endocrine axis (25–30). However a definite cause of HPA axis abnormalities is still unknown.…”

Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis

“…Basal plasma cortisol levels have been found to be generally normal [1, 17,21,33,42,45], or elevated in acutely relapsed patients [25], and elevated with a disturbed circadian rhythm and an abnormally low ACTHto-cortisol ratio [24]. In assessing dynamic features of the HPA system, highly variable and often blunted secretion of cortisol following ACTH administration at diagnostic or therapeutic doses is reported, especially in patients with long-standing MS [6, 16,21,39].…”