ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This article presents the joint European Society of Endocrinology and Endocrine Society clinical guideline on the diagnosis and treatment of Glucocorticoid (GC)-induced adrenal insufficiency

Comment: The prevalence of oral glucocorticoid (GC) use is ~1% in adults (1). The risk for glucocorticoid-induced adrenal insufficiency is evident. These guidelines provide both endocrinologists and general practitioners with guidance to manage such patients, regarding tapering of GC doses, assessing adrenal function and providing stress dosing. Any route of GC administration has potential to suppress the hypothalamic-pituitary-adrenal (HPA) axis, and suppression is dependent on the dose, duration of treatment and the potency of the GC. A meta-analysis suggested the risk of biochemical GC-induced adrenal insufficiency (AI) was 4.2% with nasal administration, 49% with oral administration, and 52% with intra-articular administration (2). However, biochemical AI is not the same as clinically-evident AI. Symptoms of AI were reported in only 10% of patients with biochemical AI (2).

Clinical question I: What is the incidence of recovery of HPA-axis function in patients with GC-induced AI? Meta-analysis (2) showed that the prevalence of AI decreased from 39% to 15% by 4 weeks after discontinuation of short-term GC therapy (< 4 weeks treatment). With moderate doses and long-term GC therapy (> 1 y) the prevalence of AI decreased from 56% to 25% by 6 months after GC discontinuation.

Clinical question II: Which clinical/biochemical parameters predict recovery of HPA-axis function in patients with GC-induced AI? Higher cortisol increments on standard ACTH stimulation testing (just after GC discontinuation) were observed in patients who recovered vs. did not recover (219 vs. 99 nmol/L) (3). Patients who recovered also had higher ambulatory morning cortisol concentrations (286 vs. 186 nmol/L) (4).

Clinical question III: What is the optimal tapering scheme? It is safe to stop GC use abruptly after short term use (< 4 weeks) of high dose GC-treatment without testing. With long-term GC use, rapid tapering can be used to reduce from supra-physiologic doses, followed by slower taper once on physiologic doses. HPA recovery is possible while on physiologic doses (4-6 mg PRED or 15-25 mg HC). Patients taking long-acting GC should be switched to short-acting when possible.

Clinical question IV: What is the diagnostic accuracy of a morning cortisol value vs. 250 mcg ACTH test? Morning cortisol values >300 nmol/L indicate a normal HPA-axis. Morning cortisol values < 150 nmol/L indicate that GC treatment should continue, with retesting after a few months. For morning cortisol values between 150-300 nmol/L, physiologic GC dosing should continue, with a retest after weeks-months.

The authors suggest that routine dynamic testing is not necessary. If dynamic testing is performed, it should be done 24-h after stopping GC treatment to avoid assay interference. If the HPA axis has not recovered after 1 year on physiologic GC doses, patients should be evaluated by an endocrinologist. Patients with current or recent GC use who have not undergone biochemical testing for AI should have stress dose GC coverage when they undergo stress.

References: 1. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford). 2011; 50(11): 1982-90. 2. Broersen LH, Pereira AM, Jørgensen JO, Dekkers OM. Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2015; 100(6): 2171-80. 3. Baek JH, Kim SK, Jung JH, Hahm JR, Jung J. Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency. Endocrinol Metab (Seoul). 2016; 31(1): 153-60. 4. Leong SH, Shander S, Ratnasingam J. Predicting Recovery of the Hypothalamic-Pituitary-Adrenal Axis After Prolonged Glucocorticoid Use. Endocr Pract. 2018; 24(1): 14-20.