Glucocorticoid Withdrawal-An Overview on When and How to Diagnose Adrenal Insufficiency in Clinical Practice

Abstract

Glucocorticoids (GCs) are widely used due to their anti-inflammatory and immunosuppressive effects. As many as 1-3% of the population are currently on GC treatment. Prolonged therapy with GCs is associated with an increased risk of GC-induced adrenal insufficiency (AI). AI is a rare and often underdiagnosed clinical condition characterized by deficient GC production by the adrenal cortex. AI can be life-threatening; therefore, it is essential to know how to diagnose and treat this disorder. Not only oral but also inhalation, topical, nasal, intra-articular and intravenous administration of GCs may lead to adrenal suppression. Moreover, recent studies have proven that short-term (<4 weeks), as well as low-dose (<5 mg prednisone equivalent per day) GC treatment can also suppress the hypothalamic-pituitary-adrenal axis. Chronic therapy with GCs is the most common cause of AI. GC-induced AI remains challenging for clinicians in everyday patient care. Properly conducted GC withdrawal is crucial in preventing GC-induced AI; however, adrenal suppression may occur despite following recommended GC tapering regimens. A suspicion of GC-induced AI requires careful diagnostic workup and prompt introduction of a GC replacement treatment. The present review provides a summary of current knowledge on the management of GC-induced AI, including diagnostic methods, treatment schedules, and GC withdrawal regimens in adults.

Keywords: adrenal insufficiency; cortisol; glucocorticoid treatment; glucocorticoid withdrawal; glucocorticoid-induced adrenal insufficiency.

Figure 1

Diagnostic algorithm for patients before and after glucocorticoid withdrawal. Diagnostic workup should never postpone the start of GC replacement treatment when suspecting adrenal crisis. Data from: Furst et al. Glucocorticoid withdrawal. UpToDate. Accessed on 29 March 2021; Fleseriu et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society Clinical Practice Guideline (2016); Pofi et al. The short synacthen (corticotropin) test can be used to predict recovery of hypothalamo–pituitary–adrenal axis function (2018). Abbreviations: AI, adrenal insufficiency; GC, glucocorticoid; SST, short stimulation test with synthetic ACTH; ¹ prednisone or equivalent; ² as described in the GC withdrawal paragraph. Δ cortisol: 30-min cortisol minus basal cortisol.