New-onset adrenal insufficiency in COVID-19 patients without preexisting adrenal disease: A systematic review

Iman Fatima, Muneeb Ali Saif, Assylzhan M. Messova, Sagira T. Abdrakhmanova, Nadiar Maratovich Mussin, Amin Tamadon

Qatar medical journal, 2026

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.5339/qmj.2026.35
Data confidence 85 high
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Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder with potential endocrine sequelae. Emerging reports suggest that adrenal insufficiency (AI) may occur in patients with COVID-19 without preexisting adrenal disease, but the clinical spectrum and strength of evidence remain unclear. To systematically review the literature on new-onset AI associated with COVID-19 in patients without prior adrenal disorders, focusing on clinical presentation, diagnostic approaches, and underlying mechanisms. Methods: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to December 28, 2025. Eligible studies included observational studies, case reports, and case series reporting AI in COVID-19 patients without known adrenal disease. Risk of bias was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute tools. Given the heterogeneity, a qualitative synthesis was conducted. Results: Nine primary studies (two observational studies and seven case reports) were included. Four narrative reviews were used solely for contextual discussion. Cases involved adults and children and occurred during acute infection or the post-COVID period. Most reports described biochemically confirmed central AI, while fewer reported primary AI due to adrenal infarction, hemorrhage, or autoimmune adrenalitis. Some presentations based mainly on steroid responsiveness were interpreted as probable critical illness-related corticosteroid insufficiency. Diagnostic thresholds and the use of ACTH stimulation testing varied. Most patients improved with glucocorticoid replacement. Conclusion: New-onset AI has been reported in temporal association with COVID-19 and may represent an infrequently reported but clinically significant endocrine manifestation. Prospective studies with standardized hormonal assessment are needed to clarify incidence, mechanisms, and screening strategies. Registration: The review was registered with PROSPERO under registration number CRD420251275141.