Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review

Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47–9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30–11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33–9.85). AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement. •Adrenal hemorrhage (AH) is included as a thrombotic manifestation in the microvascular domain of the ACR/EULAR APS criteria.•This study characterizes APS-AH via cohort analysis and systematic literature review.•APS-AH is rare but severe, with high risks of adrenal insufficiency and mortality.•Anticardiolipin IgG positivity was associated with primary adrenal insufficiency.•APS-AH is mostly diagnosed through imaging; some cases found post-mortem in catastrophic APS.