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Marcus Quinkler, Robert D Murray, Pinggao Zhang, Claudio Marelli, Robert Petermann, Andrea M. Isidori, and Bertil Ekman

Objective: This study aimed to characterize the clinical and biochemical features of patients with primary (PAI) and secondary (SAI) adrenal insufficiency who developed adrenal crises (ACs) and estimate the incidence of ACs in these patients.

Design: Retrospective case-control analysis of the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387).

Methods: 2694 patients with AI (1054 PAI; 1640 SAI) enrolled in EU-AIR. Patients who developed ≥1 AC were matched 1:3 with patients without ACs for age, sex and AI type. Data were collected at baseline and follow-up (mean±SD: PAI 3.2±1.7 years; SAI 2.9±1.7 years).

Results: 148/2694 patients (5.5%; n=84 PAI; n=64 SAI) had an AC during the study: 6.53 (PAI) and 3.17 (SAI) ACs/100 patient-years. Of patients who experienced an AC, 16% (PAI) and 9.4% (SAI) experienced ≥1 AC/year. The incidence of adverse events, infectious intercurrent illnesses and infectious serious adverse events were higher in patients with ACs than without ACs.

No differences were observed in BMI, HbA1c, blood pressure and frequencies of diabetes mellitus or hypertension between subgroups (PAI and SAI, with and without ACs). At baseline, PAI patients with AC had higher serum potassium (4.3±0.5 vs 4.2±0.4mmol/L; P=0.03) and lower sodium (138.5±3.4 vs 139.7±2.9mmol/L; P=0.004) than patients without AC. At last observation, SAI patients with AC had higher hydrocortisone doses than patients without AC (11.9±5.1 vs 10.1±2.9mg/m2; P<0.001).

Conclusions: These results demonstrate that concomitant diseases and cardiovascular risk factors do not feature in the risk profile of AC; however, patients with AC had a higher incidence of infectious events.