title: High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.
abstract: OBJECTIVE
  Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI), which according to retrospective data represents a significant clinical complication. Here we aimed to prospectively assess incidence of AC and mortality associated with AC in patients with chronic AI.
  
  
  METHODS
  A total of 423 patients with AI (primary AI, n = 221; secondary AI, n = 202) were prospectively followed up for 2 years. Baseline assessment included a general questionnaire and detailed written instructions on glucocorticoid dose adaptation during stress. Patients received follow-up questionnaires every 6 months and were contacted by phone in case of reported adrenal crisis.
  
  
  RESULTS
  A total of 423 data sets were available for baseline analysis, and 364 patients (86%) completed the whole study. Sixy-four AC in 767.5 patient-years were documented (8.3 crises per 100 patient-years). Precipitating causes were mainly gastrointestinal infection, fever, and emotional stress (20%, respectively) but also other stressful events (eg, major pain, surgery, strenuous physical activity, heat, pregnancy) or unexplained sudden onset of AC (7%) were documented. Patients with a previous AC were at higher risk of crisis (odds ratio 2.85, 95% confidence interval 1.5-5.5, P < .01). However, no further risk factors could be identified. Ten patients died during follow-up; in four cases death was associated with AC (0.5 AC related deaths per 100 patient-years).
  
  
  CONCLUSIONS
  Even in educated patients with chronic adrenal insufficiency, AC occurs in a substantial proportion of cases. Furthermore, we identified AC-associated mortality in approximately 6% of AC. Our findings further emphasize the need for improved management of AC in patients with chronic AI.
authors.affiliation: Endocrinology and Diabetes Unit (S.H., C.S., M.F., S.B.-S., K.L., D.M., B.A.), Department of Medicine I, University Hospital, and Comprehensive Heart Failure Center (S.H., M.F., B.A.), University of Wuerzburg, 97080 Wuerzburg, Germany; Department of Endocrine Research (F.B.), Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität, 80539 Munich, Germany; Division for Specific Endocrinology (H.S.W.), Medical Faculty, University Duesseldorf, 40225 Duesseldorf, Germany; and Clinical Endocrinology Unit (M.Q.), Department of Medicine, Gastroenterology, Hepatology, and Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, 10117 Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Christina
authors.initials: C
authors.lastname: Spinnler
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Stephanie
authors.initials: S
authors.lastname: Burger-Stritt
authors.forename: Katharina
authors.initials: K
authors.lastname: Lang
authors.forename: Danijela
authors.initials: D
authors.lastname: Milovanovic
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
mesh_terms: D000309:Adrenal Insufficiency / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D005938:Glucocorticoids