Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Dominic Stanculescu,Lars Larsson,Jonas Bergquist

doi:10.3389/fmed.2021.672370

Abstract

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.

Highlights

Critical illness refers to the physiological response to virtually any severe injury or infection, such as sepsis, liver disease, HIV infection, SARS-CoV-2 infection, head injury, pancreatitis, burns, cardiac surgery, etc. generally resulting in intensive care unit (ICU) hospitalization [1]
Evidence exists of some benefits from these treatments for patients suffering from either illness, when given in combination
Difficulties with finding optimal dosing and risks of causing harm to patients have contributed to controversies and limited their application for both prolonged critical illness and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Summary

INTRODUCTION

Critical illness refers to the physiological response to virtually any severe injury or infection, such as sepsis, liver disease, HIV infection, SARS-CoV-2 infection, head injury, pancreatitis, burns, cardiac surgery, etc. generally resulting in intensive care unit (ICU) hospitalization [1]. Given that a chronic suppressed HPA axis leads to adrenal atrophy—the result of prolonged under-stimulation of the adrenal glands by ACTH [178]—a switch to a “normal-cortisol” HPA-axis steady-state is necessarily a gradual process paced by the capacity for adrenal regeneration [190] In this context it is necessary to mention that some researchers have administered CRH to ME/CFS patients—not in order to Reactivation of the Somatotropic (HPS) and Thyrotropic (HPT) Axes. Researchers have injected fibromyalgia patients simultaneously with CRH, TRH, GHRH as well as GnRH— this was not done in order to assess the therapeutic potential of secretagogues but to study the patients’ endocrine dysfunctions [170] They found that the injection of the four releasing-hormones led to an “exaggerated” ACTH secretion compared to controls; this was not the case when CRH was administered alone [see above [101]]. The concurrent reactivation of endocrine axes in ME/CFS for therapeutic purposes remains largely unexplored

Intermediate Conclusions

Results in prolonged critical illness

CONCLUSION