Spironolactone for ME/CFS in a Patient Homozygous for rs5522 (I180V): A Case Report

Abstract Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with no consistently effective treatment. The mineralocorticoid receptor variant rs5522 (I180V) is associated with enhanced MR response to cortisol and altered stress responsiveness, but has not been linked to ME/CFS treatment response. Case: A 48-year-old woman with 28 years of treatment-resistant ME/CFS was found to be homozygous for rs5522. Following initiation of spironolactone, an MR antagonist, she experienced restorative sleep within 48 hours, resolution of post-exertional malaise within 3 days, and sustained functional improvement at one month. Conclusion: MR overactivity may drive ME/CFS in patients with rs5522. Genetic stratification could identify patients who benefit from MR antagonism. Keywords: myalgic encephalomyelitis/chronic fatigue syndrome, mineralocorticoid receptor, glucocorticoid receptor, rs5522, I180V, spironolactone, genetic stratification, HPA axis, cortisol, biomarker