Date Published: August 15, 2013
Publisher: BioMed Central
Author(s): Dora Liu, Alexandra Ahmet, Leanne Ward, Preetha Krishnamoorthy, Efrem D Mandelcorn, Richard Leigh, Jacques P Brown, Albert Cohen, Harold Kim.
Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing’s syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods. This comprehensive article reviews these adverse events and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.
Since their discovery in the 1940s, corticosteroids have become one of the most widely used and effective treatments for various inflammatory and autoimmune disorders (see Table 1). They are used as replacement therapy in adrenal insufficiency (at physiologic doses) as well as in supraphysiologic doses for the management of various dermatologic, ophthalmologic, rheumatologic, pulmonary, hematologic, and gastrointestinal (GI) disorders. In the field of respirology, systemic corticosteroids are used for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) and severe, uncontrolled asthma, as well as for inflammatory parenchymal lung diseases such as hypersensitivity pneumonitis and immune-mediated vasculitis. These are just some of the many important uses of this group of medications that are utilized in almost all areas of medicine.
Corticosteroids are synthetic analogues of the natural steroid hormones produced by the adrenal cortex. Like the natural hormones, these synthetic compounds have glucocorticoid (GC) and/or mineralocorticoid properties. Mineralocorticoids affect ion transport in the epithelial cells of the renal tubules and are primarily involved in the regulation of electrolyte and water balance. GCs, on the other hand, are predominantly involved in carbohydrate, fat and protein metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive effects (Table 2) .
A number of systemic corticosteroid compounds are commercially available in Canada. These agents differ with respect to potency, duration of action and ratio of mineralocorticoid to GC properties, which determine the corticosteroid’s efficacy and therapeutic use (see Table 3) [1,8].
A thorough review of corticosteroid dosing is beyond the scope of this manuscript since dosages must be individualized based on the pharmacokinetics of the different preparations, the underlying condition being treated, potential drug interactions with concurrently administered non-steroid agents, and patient response to GC treatment. In non-endocrine disorders, GCs are commonly given in pharmacologic (therapeutic) doses to suppress inflammation. In endocrine disorders, however, corticosteroid doses are often given at or close to physiologic doses (rather than in therapeutic ranges).
Systemic corticosteroids are widely used to treat a variety of autoimmune and inflammatory disorders. Despite the benefits of these agents, their prolonged use (particularly at high doses) is associated with potentially serious AEs affecting the musculoskeletal, endocrine, CV, and central nervous systems as well as the GI tract. Many of these side effects can be minimized through careful patient monitoring and implementation of preventive measures, including the use of lower potency agents and the lowest effective dose required for management of the underlying condition.
A1C: Glycated hemoglobin; ACTH: Adrenocorticotropic hormone; AE: Adverse event; AF: Atrial fibrillation; ALL: Acute lymphoblastic leukaemia; apo B: Apolipoprotein B; AS: Adrenal suppression; BG: Blood glucose; GI: Gastrointestinal; BMC: Bone mineral content; BMD: Bone mineral density; BMI: Body mass index; CBC: Complete blood count; CDA: Canadian Diabetes Association; CI: Confidence interval; COPD: Chronic obstructive pulmonary disease; CSCR: Central serous chorioretinopathy; CVD: Cardiovascular disease; DPP-4: Dipeptidyl peptidase-4; DMARD: Disease-modifying antirheumatic drug; FPG: Fasting plasma glucose; FRAX: Fracture Risk Assessment Tool; FRS: Framingham Risk Score GC, glucocorticoid; GI: Gastrointestinal; GLP-1: Glucagon-like peptide-1; HCTZ: Hydrochlorothiazide; HDL-C: High-density lipoprotein cholesterol; HPA: Hypothalamic-pituitary-adrenal; ICU: Intensive care unit; INR: International normalized ratio; ITT: Insulin tolerance test; LDL-C: Low-density lipoprotein cholesterol; NSAIDS: Non-steroidal anti-inflammatory drugs; OGTT: Oral glucose tolerance test; OR: Odds ratio; PG: Plasma glucose; PPI: Proton pump inhibitor; RR: Relative risk; SLE: Systemic lupus erythematosus; TC: Total cholesterol; TG: Triglycerides; TIA: Transient ischemic attack.
Dr. Alexandra Ahmet has received honoraria for continuing education from Nycomed. Dr. Harold Kim has received consulting fees and honoraria for continuing education from AstraZeneca, Pfizer, Merck Frosst, Novartis, and Takeda. Dr. Leanne Ward has received consultant fees from Novartis Pharmaceuticals and Amgen in the past 5 years. She has no non-financial competing interests to declare. Dr. Albert Cohen has received consulting fees and honoraria from Janssen and AbbVie. Dr. Richard Leigh has received consulting fees and honoraria for continuing education from AstraZeneca, GlaxoSmithKline, Novartis and Takeda. Dr. Jacques P. Brown has received research grants from Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-aventis, Servier, Takeda, and Warner Chilcott. He has received consulting fees or other remuneration from Amgen, Eli Lilly, Merck, Novartis, Sanofi-aventis, and Warner Chilcott, and has served on the speaker’s bureau for Amgen, Eli Lilly, and Novartis. Dr. Preetha Krishnamoorthy has received honoraria for continuing medical education from Takeda (previously Nycomed).
DL, AA, HK, LW, RL, and EM contributed to the conception, drafting and writing of the manuscript and to revising it for important intellectual content. AC, PK and JB contributed to the revision and intellectual content of this manuscript. All authors read and approved the final manuscript.