What are the potential side effects of Dexamethasone (corticosteroid) in patients, particularly those with a history of diabetes or osteoporosis?

Side Effects of Dexamethasone

Dexamethasone carries significant risks including hyperglycemia (particularly in diabetics), osteoporosis with fracture risk, gastrointestinal complications, neuropsychiatric effects, and infection susceptibility—risks that are substantially elevated in patients with pre-existing diabetes or osteoporosis. 1

Critical Considerations for High-Risk Populations

Patients with Diabetes

• Dexamethasone causes hyperglycemia and worsens diabetes control, requiring close blood glucose monitoring 1
• Blood glucose increases are dose-dependent: patients with diabetes may experience increases of approximately 32 mg/dL within 24 hours, compared to 13 mg/dL in non-diabetic patients 2
• Glucose intolerance and frank diabetes mellitus commonly develop with prolonged therapy 1
• Monitor blood glucose levels regularly, even during short courses 3

Patients with Osteoporosis

• Osteoporosis and increased fracture risk represent among the most serious complications, particularly in postmenopausal women 1
• Vertebral compression fractures occur in up to 27% of patients requiring treatment withdrawal 1
• Patients receiving high-dose steroids (daily dose ≥15 mg prednisone equivalent, cumulative exposure >1 g) have substantially increased fracture risk 4
• Baseline DEXA scan should be obtained before starting therapy in patients at increased fracture risk 4
• Annual bone mineral density testing is recommended for patients on long-term therapy 1

Dose-Dependent Side Effects by Duration

Short-Term Use (Days to Weeks)

• Gastrointestinal complications: High-dose dexamethasone (96 mg loading dose) caused serious gastrointestinal side effects in 14.3% of patients, including fatal ulcer hemorrhage, rectal bleeding, and gastrointestinal perforation 5
• Gastric irritation and increased peptic ulcer risk occur even with short courses 1
• Hypertension can develop or worsen quickly 1
• Weight gain and fluid retention often occur within the first few weeks 1
• Facial rounding (moon face) can begin developing even during short-term use 1
• Neuropsychiatric effects: Insomnia, restlessness, nervousness occur in >30% of patients; mood disturbances range from euphoria to severe depression and psychosis 1, 6

Long-Term Use (Months to Years)

• Osteoporosis with vertebral compression fractures 1
• Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 1
• Redistribution of body fat with truncal obesity, moon facies, and buffalo hump occurs in 80% of patients after two years 1
• Posterior subcapsular cataracts and increased intraocular pressure/glaucoma develop with prolonged use 1
• Myopathy affecting diaphragmatic and intercostal muscles 1
• Adrenal insufficiency upon withdrawal 6
• Increased risk of both opportunistic and non-opportunistic infections 1

Cardiovascular and Metabolic Effects

• Hypertension: Dexamethasone elevates blood pressure through mineralocorticoid-like effects, direct increase in cellular potassium efflux, and promotion of atherosclerosis 3
• Dyslipidemia occurs with long-term use, increasing cardiovascular disease risk 1
• Higher doses (≥5 mg prednisone equivalent) are associated with increased cardiovascular event risk 1
• Regular blood pressure monitoring is essential, even during short courses 3

Infection Risk

• Increased susceptibility to both opportunistic and non-opportunistic infections, including pneumonia, skin infections, and sepsis 1
• Consider Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone equivalent for ≥4 weeks 1
• Update all vaccines before starting therapy; avoid live vaccines once immunosuppressed 1
• High-dose glucocorticoids (>20 mg/day prednisone equivalent) adversely impact vaccine responses 1

Ophthalmologic Complications

• Posterior subcapsular cataracts develop with prolonged use 1
• Increased intraocular pressure and glaucoma can occur 1
• Regular eye examinations are essential for patients on long-term therapy 1
• Corticosteroids should be used cautiously in patients with ocular herpes simplex due to risk of corneal perforation 6

Critical Drug Interactions and Precautions

• Phenytoin, phenobarbital, ephedrine, and rifampin enhance metabolic clearance of dexamethasone, requiring dose adjustment 6
• Monitor prothrombin time frequently when combining with coumarin anticoagulants, as corticosteroids alter anticoagulant response 6
• Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia 6
• When combined with potassium-depleting diuretics, monitor closely for hypokalemia 6

Special Populations

Elderly Patients

• Require more careful monitoring and often lower doses due to increased risk of complications 1

Patients with Cirrhosis or Hypothyroidism

• Enhanced effect of corticosteroids occurs in these populations 6

Children

• Growth suppression is a significant concern with long-term therapy 1
• Growth and development should be carefully monitored 6

Conditions Requiring Cautious Use

Use dexamethasone with extreme caution in patients with: 6

• Nonspecific ulcerative colitis (risk of perforation)
• Diverticulitis
• Fresh intestinal anastomoses
• Active or latent peptic ulcer
• Renal insufficiency
• Myasthenia gravis
• Existing emotional instability or psychotic tendencies

Withdrawal Syndrome

• Following prolonged therapy, withdrawal may result in corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise—even without evidence of adrenal insufficiency 6
• When dose reduction is possible, it must be gradual 6

Monitoring Requirements for High-Risk Patients

For patients with diabetes: 1, 3

• Baseline blood glucose assessment
• Regular blood glucose monitoring during therapy
• Intensification of diabetes management as needed

For patients with osteoporosis: 4, 1

• Baseline DEXA scan before starting therapy
• Supplemental calcium (1200 mg/day) and vitamin D3 (800-1000 IU/day)
• Consider treatment with denosumab (60 mg subcutaneously every 6 months), zoledronic acid (5 mg intravenously annually), or alendronate (70 mg orally weekly)
• Follow-up DEXA scan after 1 year of therapy
• Regular assessment for vertebral compression fractures

For all patients on dexamethasone: 1, 3

• Regular blood pressure monitoring
• Weight monitoring to detect fluid retention
• Ophthalmologic evaluation for long-term users
• Assessment for signs of infection