What are the common systemic side effects of oral or intravenous glucocorticoids and how should they be monitored and prevented?

Systemic Glucocorticoid Side Effects: Monitoring and Prevention

Systemic glucocorticoids cause serious, dose-dependent complications affecting nearly every organ system, with severe reactions occurring in approximately 6% of patients and mild-to-moderate reactions in 28%, requiring proactive monitoring and prevention strategies from the outset of therapy. 1, 2

Immediate and Short-Term Side Effects (Days to Weeks)

Metabolic and Endocrine

• Hyperglycemia and diabetes exacerbation occur commonly, requiring blood glucose monitoring even during short courses, particularly in diabetic patients who may need adjustment of antidiabetic medications 3, 1
• Increased appetite and rapid weight gain develop within the first few weeks of therapy 3, 1
• Weight monitoring is essential to detect rapid fluid retention 1

Gastrointestinal

• Gastric irritation occurs in 21-32% of patients and can be ameliorated with H2-receptor antagonists 1
• Pancreatitis is a rare but documented adverse effect 3, 4

Neuropsychiatric

• Psychiatric disturbances are extremely common, with insomnia, restlessness, and nervousness occurring in more than 30% of patients 3, 1
• Short-term therapy typically causes euphoria and hypomania, while long-term therapy tends to induce depressive symptoms 2
• Behavioral changes including irritability, fussiness, and personality changes occur in up to 29% of patients 1
• Mood swings and frank psychosis are possible, with dosage directly related to incidence but not to timing, severity, or duration of effects 3, 2

Cardiovascular

• Hypertension develops commonly and requires regular blood pressure monitoring for all patients 3, 1
• Fluid retention and facial swelling occur frequently 3

Other Acute Effects

• Acne, blurred vision, easy bruising, increased body hair growth, and muscle weakness are common 3
• Lower resistance to infection develops early 3

Long-Term and Severe Complications (Months to Years)

Musculoskeletal (Most Serious)

• Osteoporosis and increased fracture risk are among the most serious complications, with vertebral compression fractures occurring in up to 27% of patients requiring treatment withdrawal 1
• Recent (within 12 months) and prolonged (≥90 days) use is independently associated with reduced bone mineral density and increased fracture risk 4
• Aseptic necrosis of femoral and humoral heads can develop even at moderate doses 1
• Osteonecrosis and fractures occur more commonly in patients with preexisting bone or joint problems 3
• Steroid myopathy affecting diaphragmatic and intercostal muscles may occur 1

Ophthalmologic

• Posterior subcapsular cataracts develop with prolonged use 3, 1
• Glaucoma and increased intraocular pressure can occur, requiring regular ophthalmologic evaluation 3, 1

Immunologic

• Increased risk of both opportunistic and non-opportunistic infections, including pneumonia, skin infections, and sepsis 1
• Rare cases of Pneumocystis carinii pneumonia have been reported, with some experts advocating prophylaxis with trimethoprim-sulfamethoxazole 1

Endocrine

• Adrenal suppression is a critical concern requiring stress-dose steroids for surgical patients on long-term therapy 4, 1
• Cushing's syndrome develops with prolonged use 5

Cardiovascular (High-Risk Mortality Data)

• In high-risk populations with severe comorbidities treated with very high-dose intravenous methylprednisolone, mortality has been documented from cardiac arrest, infection, and congestive heart failure 1

Critical Monitoring Algorithm

Baseline Assessment (Before Starting Therapy)

• Blood pressure measurement 1
• Fasting blood glucose (especially in diabetics or pre-diabetics) 1
• Baseline weight 1
• Bone mineral density (DEXA scan) if anticipating long-term therapy 1
• Ophthalmologic examination if anticipating long-term therapy 1
• Update all vaccines before starting immunosuppressive therapy; avoid live vaccines once started 1

During Therapy Monitoring

• Blood pressure: Periodically throughout treatment 3, 1
• Blood glucose: Regularly, particularly in diabetic patients 3, 1
• Weight: At each visit to detect fluid retention 1
• Growth parameters (height, weight) in pediatric patients 3, 1
• Morning cortisol levels if prolonged use or concern for adrenal suppression 1

Long-Term Therapy Monitoring (>3 months)

• Annual DEXA scans for bone mineral density 1
• Regular ophthalmologic examination for cataracts and glaucoma 1
• Infection surveillance: Patient education about increased risk and when to seek care 1

Prevention and Risk Mitigation Strategies

Dosing Principles

• Use the lowest possible dose for the shortest duration to control the condition 3, 1, 6
• Doses exceeding 10 mg prednisone daily for more than 18 months significantly increase risk of severe complications 1
• Begin tapering 2 weeks after complete remission rather than continuing high doses unnecessarily 3
• High-dose glucocorticoid treatment should be given for no longer than 16 weeks 3
• Consider alternate-day therapy when appropriate to reduce adrenal suppression 1

Bone Protection

• Initiate calcium and vitamin D supplementation for all patients anticipated to receive at least 5 mg prednisone equivalent for at least 3 months 1
• This is mandatory, not optional, for bone protection 1

Gastrointestinal Protection

• Consider H2-receptor antagonists to prevent gastric irritation, particularly in patients with history of peptic ulcer disease 1

Patient Education (Critical)

• Provide steroid card or similar notification listing emergency-care considerations for acute medical presentation, fracture, serious infection, need for surgery, or general anesthesia 3
• Do not stop taking corticosteroids suddenly 6
• Seek medical attention if becoming unwell 6
• Awareness of increased susceptibility to infections, especially chickenpox 6
• Dietary modification: low calorie, low sodium, high potassium 6
• Single morning dose to minimize adrenal suppression 6

Route and Frequency Individualization

• Daily oral glucocorticoids are most commonly used, but every-other-day oral glucocorticoids can be used safely in some conditions 3
• Intravenous steroids may be beneficial in the presence of bowel edema 3

Common Pitfalls to Avoid

• Underestimating the impact of sleep disturbances and mood changes on quality of life, which occur in >30% of patients 1
• Failing to recognize that increasing the dose in poorly responsive patients confers little additional benefit and is significantly more toxic 1
• Not providing stress-dose steroids for surgical patients on long-term therapy, risking adrenal crisis 1
• Inadequate patient education about infection risk and when to seek care 1
• Failing to initiate bone protection early in patients anticipated to require prolonged therapy 1
• Not monitoring blood glucose in non-diabetic patients, assuming they are not at risk 1

Special Population Considerations

Patients with Diabetes

• Particularly high risk for hyperglycemia requiring intensive glucose monitoring 1
• May require adjustment of antidiabetic medications 1

Pediatric Patients

• May experience growth suppression requiring linear growth monitoring 3, 1
• Almost all children experience "catch-up" growth after completion of therapy 3, 1

Patients with Pre-existing Conditions

• Patients with pre-existing hypertension, diabetes, or cardiovascular disease are at particularly high risk for serious complications 1
• Patients with bone or joint problems have increased risk of osteonecrosis and fractures 3

When to Consider Alternative Therapies

Repeated or prolonged exposure to glucocorticoids should be avoided in patients relapsing more than infrequently, and alternative therapies including cyclophosphamide, rituximab, calcineurin inhibitors, or mycophenolic acid analogs should be used instead 3

The side effects of long-lasting steroid therapy can be very serious and irreversible, making careful patient monitoring and proactive prevention strategies mandatory rather than optional 3