Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation

The study explored autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) by examining hemodynamic responses, peripheral skin temperature rhythms, and endothelial function. In this cross-sectional case-control study, 67 female ME/CFS patients and 48 female healthy controls underwent a 10-minute passive standing test (NASA lean test), 7-day actigraphy for wrist temperature and activity rhythms, and blood sampling for endothelial biomarkers. ME/CFS patients exhibited significantly higher supine systolic and diastolic blood pressure and heart rate, along with elevated levels of endothelin-1 (ET-1, p=0.004) and vascular cell adhesion molecule-1 (VCAM-1, p<0.001) compared to controls. While no group differences were found in the postural hemodynamic responses or overall wrist temperature rhythms, ME/CFS patients had lower activity rhythm mesor and amplitude. A key finding was that circulating ET-1 levels in ME/CFS were significantly associated with worse scores on self-reported measures of fatigue, sleep quality, anxiety/depression, and autonomic symptoms. Furthermore, a discriminant analysis using diastolic blood pressure, ET-1, VCAM-1, and wrist temperature rhythm variables correctly classified 96% of ME/CFS patients and 85% of healthy controls. The study's limitations include its single-center design, small sample size, restriction to women with mild/moderate disease, and lack of data on potential confounders like menstrual cycle stage and metabolic factors, which prevents causal inference.