What are the adverse effects of systemic glucocorticoids (corticosteroids)?

From the Guidelines

Systemic glucocorticoids can cause numerous adverse effects with both short-term and long-term use, and it is essential to consider these risks when initiating therapy, as highlighted in a 2020 study 1.

Adverse Effects of Systemic Glucocorticoids

The adverse effects of systemic glucocorticoids can be categorized into short-term and long-term effects. Common short-term side effects include:

• Increased appetite
• Weight gain
• Fluid retention
• Mood changes (including euphoria, anxiety, and irritability)
• Insomnia
• Hyperglycemia With prolonged use, more serious complications develop, including:
• Osteoporosis
• Increased fracture risk
• Adrenal suppression
• Muscle weakness
• Skin thinning
• Easy bruising
• Impaired wound healing
• Increased susceptibility to infections Metabolic effects include:
• Diabetes
• Dyslipidemia
• Redistribution of body fat (cushingoid appearance with central obesity, moon face, and buffalo hump) Cardiovascular complications include:
• Hypertension
• Increased risk of atherosclerosis Ocular effects include:
• Cataracts
• Glaucoma Neuropsychiatric effects range from mood disorders to psychosis in susceptible individuals. Children may experience growth suppression.

Minimizing Risks

The risk of these adverse effects increases with higher doses, longer duration of treatment, and systemic rather than topical or inhaled administration. Strategies to minimize these risks include:

• Using the lowest effective dose for the shortest duration possible
• Alternate-day dosing when appropriate
• Calcium and vitamin D supplementation, as recommended in a 2007 study 1
• Bone density monitoring
• Gradual tapering when discontinuing therapy to prevent adrenal crisis, as suggested in a 2014 study 1 It is crucial to weigh the benefits and risks of systemic glucocorticoid therapy and to closely monitor patients for potential adverse effects, as emphasized in the 2020 study 1.

From the FDA Drug Label

ADVERSE REACTIONS (listed alphabetically, under each subsection) The following adverse reactions have been reported with prednisone or other corticosteroids: Allergic Reactions anaphylactoid or hypersensitivity reactions, anaphylaxis, angioedema Cardiovascular System bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, ECG changes caused by potassium deficiency, edema, fat embolism, hypertension or aggravation of hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS: Cardio-Renal), necrotizing angiitis, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis Dermatologic acne, acneiform eruptions, allergic dermatitis, alopecia, angioedema, angioneurotic edema, atrophy and thinning of skin, dry scaly skin, ecchymoses and petechiae (bruising), erythema, facial edema, hirsutism, impaired wound healing, increased sweating, Karposi’s sarcoma (see PRECAUTIONS: General Precautions), lupus erythematosus-like lesions, perineal irritation, purpura, rash, striae, subcutaneous fat atrophy, suppression of reactions to skin tests, striae, telangiectasis, thin fragile skin, thinning scalp hair, urticaria (associated symptoms include; arthralgias, buffalo hump, dizziness, life-threatening hypotension, nausea, severe tiredness or weakness) amenorrhea, postmenopausal bleeding or other menstrual irregularities, decreased carbohydrate and glucose tolerance, development of cushingoid state, diabetes mellitus (new onset or manifestations of latent), glycosuria, hyperglycemia, hypertrichosis, hyperthyroidism (see WARNINGS: Endocrine), hypothyroidism, increased requirements for insulin or oral hypoglycemic agents in diabetics, lipids abnormal, moon face, negative nitrogen balance caused by protein catabolism, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness) (see WARNINGS: Endocrine), suppression of growth in pediatric patients Fluid and Electrolyte Disturbances congestive heart failure in susceptible patients, fluid retention, hypokalemia, hypokalemic alkalosis, metabolic alkalosis, hypotension or shock-like reaction, potassium loss, sodium retention with resulting edema Gastrointestinal abdominal distention, abdominal pain, anorexia which may result in weight loss, constipation, diarrhea, elevation in serum liver enzyme levels (usually reversible upon discontinuation), gastric irritation, hepatomegaly, increased appetite and weight gain, nausea, oropharyngeal candidiasis, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis, vomiting. Hematologic anemia, neutropenia (including febrile neutropenia). Metabolic negative nitrogen balance due to protein catabolism Musculoskeletal arthralgias, aseptic necrosis of femoral and humeral heads, increase risk of fracture, loss of muscle mass, muscle weakness, myalgias, osteopenia, osteoporosis (see PRECAUTIONS: Musculoskeletal), pathologic fracture of long bones, steroid myopathy, tendon rupture (particularly of the Achilles tendon), vertebral compression fractures onvulsions, delirium, dementia (characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance), depression, dizziness, EEG abnormalities, emotional instability and irritability, euphoria, hallucinations, headache, impaired cognition, incidence of severe psychiatric symptoms, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, increased motor activity, insomnia, ischemic neuropathy, long-term memory loss, mania, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders including steroid psychoses or aggravation of preexisting psychiatric conditions, restlessness, schizophrenia, verbal memory loss, vertigo, withdrawn behavior Ophthalmic blurred vision, cataracts (including posterior subcapsular cataracts), central serous chorioretinopathy, establishment of secondary bacterial, fungal and viral infections, exophthalmos, glaucoma, increased intraocular pressure (see PRECAUTIONS: Ophthalmic), optic nerve damage, papilledema Other abnormal fat deposits, aggravation/masking of infections, decreased resistance to infection (see WARNINGS: Infection), hiccups, immunosuppression, increased or decreased motility and number of spermatozoa, malaise, insomnia, moon face, pyrexia.

The adverse effects of systemic glucocorticoids include:

• Cardiovascular effects: bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure
• Dermatologic effects: acne, acneiform eruptions, allergic dermatitis, alopecia, angioedema
• Endocrine effects: development of cushingoid state, diabetes mellitus, hyperglycemia, hypertrichosis, hypothyroidism
• Gastrointestinal effects: abdominal distention, abdominal pain, anorexia, constipation, diarrhea
• Hematologic effects: anemia, neutropenia
• Metabolic effects: negative nitrogen balance due to protein catabolism
• Musculoskeletal effects: arthralgias, aseptic necrosis of femoral and humeral heads, increase risk of fracture, loss of muscle mass, muscle weakness
• Neurologic effects: convulsions, delirium, dementia, depression, dizziness, EEG abnormalities
• Ophthalmic effects: blurred vision, cataracts, central serous chorioretinopathy, establishment of secondary bacterial, fungal and viral infections
• Other effects: abnormal fat deposits, aggravation/masking of infections, decreased resistance to infection, hiccups, immunosuppression, increased or decreased motility and number of spermatozoa, malaise, insomnia, moon face, pyrexia 2.

From the Research

Adverse Effects of Systemic Glucocorticoids

• Systemic glucocorticoids can produce significant morbidity for patients due to their multiple side effects 3
• The side effects of systemic glucocorticoids can be managed and prevented with proper counseling, prophylaxis, and treatment 3
• Short-term systemic glucocorticoid administration can lead to metabolic side effects, drug interactions, and adverse reactions 4
• Glucocorticoid-induced osteoporosis is a significant concern, and bisphosphonates can be used to prevent and treat it 5, 6
• However, the long-term effects of bisphosphonates on bone quality and fracture risk reduction in patients with glucocorticoid-induced osteoporosis remain uncertain 6
• Local glucocorticoid injections can also have systemic side effects, including Cushing syndrome, loss of bone density, infection, and hyperglycemia 7
• The systemic absorption and clinical effects of locally injected glucocorticoids can vary significantly between individuals 7
• Caution should be exercised when using local glucocorticoid injections in higher risk patients, such as postmenopausal women, people with diabetes, and those considering surgery in the near term 7

Specific Adverse Effects

• Osteoporosis and osteonecrosis are significant concerns with long-term glucocorticoid use 3
• Hyperglycemia is a common side effect of short-term systemic glucocorticoid administration 4
• Atrial fibrillation, osteonecrosis of the jaw, upper gastrointestinal adverse events, and esophageal cancer risk are potential adverse events associated with bisphosphonate therapy in patients with glucocorticoid-induced osteoporosis 5
• Loss of bone density and infection are potential complications of local glucocorticoid injections 7