Adrenal insufficiency is first manifestation in 73.6% of APS patients with adrenal involvement

Adrenal involvement is a rare but potentially severe immunothrombotic manifestation of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE)-spectrum disease. Because the term adrenal crisis should be reserved for patients with acute adrenal insufficiency accompanied by hypotension or shock, this review distinguishes adrenal vascular injury, adrenal insufficiency, and strict adrenal crisis. We performed a systematic review and individual-patient pooled analysis of published cases of APS/SLE-spectrum adrenal involvement through March 31, 2026. The initial database search was performed from inception to February 10, 2026 and was updated through March 31, 2026. The study selection followed PRISMA 2020 principles, and the protocol was registered in PROSPERO (CRD420261298329). Published patients were harmonized for diagnosis stratum, precipitating trigger, adrenal imaging phenotype, adrenal insufficiency chronology, immunologic profile, thrombotic burden, treatment/follow-up variables, CAPS presentation context, and outcomes. A total of 103 studies comprising 155 published patients were included; 143 entered the main analysis set. The median age was 43.8 years, 49.0% were female, and primary APS accounted for 67.1% of the main cohort. Hemorrhage-dominant adrenal injury was the leading imaging phenotype (66.9%), bilateral adrenal involvement was highly prevalent (86.3% of informative cases), and adrenal insufficiency was the first manifestation in 73.6% of informative cases. Among codable main-analysis cases, hypotension was documented in 60/125 (48.0%), strict adrenal crisis in 64/124 (51.6%), hyponatremia in 47/142 (33.1%), and hyperkalemia in 57/134 (42.5%). CAPS was treated as a presentation/severity context rather than as a downstream consequence and was reported in 59.8% of evaluable patients. Adrenal involvement in APS and lupus-spectrum disease is a heterogeneous but clinically recognizable high-risk phenotype characterized by bilateral adrenal injury, hemorrhagic predominance, frequent sentinel presentation as adrenal insufficiency, and substantial CAPS burden. Careful terminology helps separate adrenal vascular injury, adrenal insufficiency, and strict adrenal crisis while preserving the need for urgent endocrine rescue and systemic thrombotic evaluation. https://www.crd.york.ac.uk/prospero/, identifier CRD420261298329.