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.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…This proposal is consistent with descriptions of ME/CFS as a progression from a hypermetabolic to hypometabolic state (21). It also aligns with a recent hypothesis relating many of the symptoms in severe ME/CFS to impaired pituitary function (111). Further support for this proposal is provided by the many previous ME/CFS studies that have documented dysfunctions in the hypothalamic-pituitary-somatotropic (HPS) axis (112)(113)(114), the HPT axis (115)(116)(117)(118)(119)(120), and the HPA axis (121-136)-notably associated with inflammation and oxidative & nitrosative stress (O&NS) (137)(138)(139)(140).…”

“…Similarly, the administration of ghrelin to the I/R rats “inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival” ( 200 ). The sequence between intestinal injury, ghrelin secretion and GH release by the pituitary could be particularly relevant for solving ME/CFS given that “several of the main typical symptoms in severe ME/CFS, such as fatigue, myalgia, contractility, delaying muscle recovery and function, exertional malaise, neurocognitive dysfunction, and physical disability may be related to severe GH deficiency” ( 111 ).…”

Development and Pilot Testing of a Smartphone-Based Self-Care Program for Patients with Chronic Hepatitis B

“…A previous study on Korean patients with the HBV reported that patients with higher fatigue levels had lower levels of cortisol [ 16 ]. This pattern of cortisol is similar to that of chronic fatigue syndrome [ 39 ]. To better assess the effects of the Hep B Care ® program on fatigue as one of the major symptoms in individuals with the HBV, further studies will need to be conducted with objective outcome indicators using a wider range of biomarkers.…”

Neuroimmunoendocrinology of SARS-CoV-2 Infection

“…None of the controls indicated an APA- or AHA-positive result. This study concluded that COVID-19 may cause secondary or tertiary adrenal insufficiency and that pituitary/ hypothalamic autoimmunity may play a role in this dysfunction; thus, a routine screening of adrenal function, as well as AHA and APA evaluations in these patients, should be recommended [ 30 , 31 , 32 ]. Considering these results, even if studies on the pituitary involvement in acute phase of this infection are scarce, a sequela of pituitary dysfunction, especially linked to pituitary autoimmunity in patients hospitalized from the acute phase of this infectious disease, could not be excluded.…”