Glucocorticoid-induced adrenal insufficiency

Abstract: Background: Glucocorticoids (GCs) are effective in treating many diseases and are widely used. However, glucocorticoid treatment can down-regulate the hypothalamic-pituitary-adrenal axis and lead to glucocorticoid-induced adrenal insufficiency. This thesis aimed to investigate the prevalence of oral GC prescriptions, related mortality, and the prevalence of GC-induced adrenal insufficiency during topical GC treatment and during intermittent high-dose GC therapy. Methods: Individuals, living in Västra Götaland county, with prescriptions of prednisolone ≥5 mg/day (or equivalent dose of other GCs) for ≥21 days during 2007–2014 were identified in The Swedish Prescribed Drug Register. By using a personal identification number, patients were cross-linked with four other Swedish registries to collect information on indication for GC treatment, comorbidities, and cause-of death. To study if death was related to GC-induced adrenal insufficiency, medical records from 300 patients who died from sepsis were investigated. Twenty-seven patients with oral lichen planus receiving topical GC were studied and in a prospective study 10 adults with lymphoma receiving intermittent, high-dose GC were included. Results: During 2007–2014, 14.1% of inhabitants (n=223 211) in Western Sweden received prescriptions for oral GCs at doses associated with risk of developing GC-induced adrenal insufficiency. GC users had a 2-fold overall risk of dying compared to controls (adjusted hazard ratio 2.1, 95% confidence interval 2.0–2.1). Under- and undiagnosed GC-induced adrenal insufficiency possibly contributed to the death in 47 of 300 (16%) patients considered to have died from sepsis. Approximately 20% of patients receiving chronic topical GCs in the oral cavity had GC-induced adrenal insufficiency. None of the patients receiving intermittent high-dose GC therapy had GC-induced adrenal insufficiency. Conclusion: Oral GC treatment is common and can lead to GC-induced adrenal insufficiency and increased mortality. GC-induced adrenal insufficiency is underdiagnosed and awareness is essential for the diagnosis and treatment.