Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies

Abstract

Objective: Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here, we evaluated frequency, causes and risk factors of AC in patients with chronic AI. Methods: In a cross-sectional study, 883 patients with AI were contacted by mail. Five-hundred and twenty-six patients agreed to participate and received a disease-specific questionnaire. Results: Four-hundred and forty-four datasets were available for analysis (primary AI (PAI), nZ254; secondary AI (SAI), nZ190). Forty-two percent (PAI 47% and SAI 35%) reported at least one crisis. Three hundred and eighty-four AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat and pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6% and SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5 vs 28.4%, PZ0.003). Crisis incidence was not influenced by educational status, body mass index, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or GH deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of crisis (odds ratio (OR)Z2.02, 95% confidence interval (CI) 1.05-3.89, PZ0.036). In SAI, female sex (ORZ2.18, 95% CI 1.06-4.5, PZ0.035) and diabetes insipidus (ORZ2.71, 95% CI 1.22-5.99, PZ0.014) were associated with higher crisis incidence. Conclusion: AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of crisis prevention in patients with AI.

Adrenal Crisis: Still a Deadly Event in the 21st Century

“…( Table 3), [15][16][17][18] greater than other infections or febrile illnesses. This is likely because it directly affects the intestinal absorption of glucocorticoids taken orally.…”

“…31 Diabetes insipidus was also associated with higher risk of adrenal crisis in patients with secondary adrenal insufficiency, which could be due to the higher risk of dehydration, or the lack of V1-receptor mediated vasoconstriction during severe stress. 16 Other medical conditions (eg, type 1 and type 2 diabetes mellitus, hypogonadism) were associated with higher risk of adrenal crisis in some studies, although the mechanism is not clear ( Table 4). 15,17 The life-time risk of adrenal crisis in a patient with adrenal insufficiency is about 50%, 17 and those with previous adrenal crisis appear to be at greater risk of subsequent episodes.…”

“…[15][16][17] These estimates were based on retrospective studies using questionnaires, and limited by reporting bias. A recent prospective study 18 found 64 episodes of adrenal crisis in 423 patients with primary and secondary adrenal insufficiency (8.3 adrenal crises/100 PYs), and, alarmingly, 4 adrenal crisis-related deaths were noted over a follow-up period of 2 years (0.5 adrenal crisis-related deaths per 100 PYs).…”

“…[15][16][17][18] Gastrointestinal illness is consistently the largest precipitating factor for adrenal crisis …”

“…Patients with primary adrenal insufficiency may be at higher risk of adrenal crisis than patients with secondary adrenal insufficiency, due to the lack of mineralocorticoids and greater risk of dehydration and hypovolemia. 15,16,18 The true risk of adrenal crisis in patients with glucocorticoid-induced adrenal insufficiency is difficult to determine, as they form a heterogeneous group and only limited case reports are available. 22,23 It is important, nevertheless, to recognize that the most common cause of adrenal insufficiency is use of exogenous steroids, 3 and these patients are similarly at risk of adrenal crisis.…”