Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland's pulsatile secretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a “reactivation” of the pituitary gland's pulsatile secretion of tropic hormones, or (b) the interruption of the “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients—and the resulting positive metabolic effects—could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones—including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis—also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS.

We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research. Specifically, we combine emerging findings regarding (a) hypoperfusion and endotheliopathy, and (b) intestinal injury in these illnesses with our previously published hypothesis about the role of (c) pituitary suppression, and (d) low thyroid hormone function associated with redox imbalance in ME/CFS. Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS. New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.