Hypothalamic-Pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome

Abstract:

Context: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe chronic illness which reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized.

Objective: To investigate the occurrence of anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients.

Design, setting, patients and other participants: This is a case-control study conducted in University Hospital setting (Stanford, Naples). Thirty women with ME/CSF (Group 1) diagnosed according to Fukuda, Canadian, and IOM criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls.

Main outcome measures: APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands and plasma and urinary osmolality. Both APA and AHA titers were assessed and the prevalence of pituitary hormone deficiencies was also investigated.

Results: Patients in Group 1 showed a high prevalence of AHA (33%) and APA (56%) and a significant lower levels of ACTH/cortisol, and GH peak/IGF1 vs controls (all AHA/APA negative). Patients in Group 1A (13 patients positive at high titers, ≥1:32) showed ACTH/cortisol and GH peak/ IGF1 levels significantly lower and more severe forms of ME/CFS with respect to patients in Group 1B (7 positive at middle/low titers,1:16-1:8) and 1C (10 Ab negative patients).

Conclusions: Both AHA and/or APA at high titers associated with hypothalamic/pituitary dysfunction suggest that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Source: De Bellis A, Bellastella G, Pernice V, Cirillo P, Longo M, Maio A, Scappaticcio L, Maiorino MI, Bellastella A, Esposito K, Montoya JG. Hypothalamic-Pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome. J Clin Endocrinol Metab. 2021 Jul 13:dgab429. doi: 10.1210/clinem/dgab429. Epub ahead of print. PMID: 34254637. https://pubmed.ncbi.nlm.nih.gov/34254637/

The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients

Abstract:

BACKGROUND: Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS) has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased alpha-MSH plasma levels may also occur in CFS patients. We therefore examined alpha-MSH levels in CFS patients.

METHODS: Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of alpha-MSH, adrenocorticotropic hormone (ACTH), serum cortisol and dehydroepiandrosterone sulfate (DHEA-S). Mean levels of alpha-MSH were compared between the CFS and control groups using Welch’s t test.

RESULTS: The mean plasma alpha-MSH concentration in the CFS group (17.9 +/- 1.0 pg/mL) was significantly higher than that in healthy controls (14.5 +/- 1.0 pg/mL, p = 0.02). However, there was a wide range of values in the CFS group. The factors correlated with the plasma alpha-MSH values were analyzed using Spearman’s rank correlation. A negative correlation was found between the duration of the CFS and the plasma alpha-MSH values (p = 0.04, rs = -0.28), but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively). The CFS patients were divided into two groups: patients diagnosed for <or= 5 years’ duration, and those diagnosed for 5-10 years’ duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean alpha-MSH concentration in the <or= 5 years group was 20.8 +/- 1.2 pg/mL, which was significantly higher than that in the healthy controls (p < 0.01). There was no significant difference between the 5-10 year group (15.6 +/- 1.4 pg/mL) and the healthy controls.

CONCLUSIONS:CFS patients with a disease duration of <or= 5 years had significantly higher levels of alpha-MSH in their peripheral blood. alpha-MSH could be a potent biological marker for the diagnosis of CFS, at least during the first 5 years after onset of the disease.

 

Source: Shishioh-Ikejima N, Ogawa T, Yamaguti K, Watanabe Y, Kuratsune H, Kiyama H. The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients. BMC Neurol. 2010 Aug 23;10:73. doi: 10.1186/1471-2377-10-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933583/ (Full article)