Are patients on lifelong steroid replacement therapy at increased risk of steroid-related complications?

From the Guidelines

Yes, patients on lifelong steroid replacement therapy are at increased risk of steroid-related complications, but these risks can be mitigated with proper management and monitoring. The risk of complications, such as osteoporosis, glucose intolerance, and cardiovascular disease, increases with higher doses or prolonged use of steroids 1. To minimize these risks, clinicians should use the lowest effective dose, consider alternate-day therapy when possible, and monitor for early signs of complications through regular bone density scans, blood glucose testing, and blood pressure measurements 1. Additionally, patients should be educated about proper stress dosing to avoid overuse and provided with preventive measures, such as calcium and vitamin D supplements, to reduce the risk of osteoporosis 1. The underlying mechanism for these complications relates to glucocorticoids' effects on multiple body systems, including metabolism, bone remodeling, and immune function, even when attempting to replicate normal physiologic levels. Some key points to consider in managing patients on lifelong steroid replacement therapy include:

• Using the lowest effective dose to minimize complications
• Monitoring for early signs of complications, such as osteoporosis and glucose intolerance
• Providing preventive measures, such as calcium and vitamin D supplements
• Educating patients about proper stress dosing to avoid overuse
• Considering alternate-day therapy when possible to reduce the risk of complications. It is essential to weigh the benefits of steroid replacement therapy against the potential risks and to individualize treatment plans to minimize complications and optimize patient outcomes 1.

From the FDA Drug Label

ADVERSE REACTIONS Most adverse reactions are caused by the drug’s mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis When fludrocortisone is used in the small dosages recommended, the glucocorticoid side effects often seen with cortisone and its derivatives are not usually a problem; however, the following untoward effects should be kept in mind, particularly when fludrocortisone is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid Musculoskeletal—muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones, and spontaneous fractures.

WARNINGS In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Corticosteroids may mask some signs of infection, and new infections may appear during their use.

Patients on lifelong steroid replacement therapy are at increased risk of steroid-related complications, including:

• Musculoskeletal complications such as muscle weakness, steroid myopathy, and osteoporosis
• Infections due to suppressed immune system
• Metabolic complications such as hyperglycemia and glycosuria
• Ophthalmic complications such as posterior subcapsular cataracts and glaucoma
• Dermatologic complications such as impaired wound healing and thin fragile skin 2 3

From the Research

Steroid Replacement Therapy and Complications

Patients on lifelong steroid replacement therapy may be at increased risk of steroid-related complications. The following points highlight some of the potential risks:

• Bone mineral density loss: Studies have shown that patients on long-term steroid replacement therapy are at risk of developing osteoporosis and osteopenia, particularly at higher doses 4.
• Kidney function decline: Research suggests that steroid replacement therapy may be associated with a higher risk of kidney function decline, including a 67% higher risk of kidney outcome compared to those not on steroid replacement therapy 5.
• Adrenal insufficiency: Long-term corticosteroid use can lead to secondary adrenal insufficiency, which can be life-threatening in the event of an adrenal crisis 6.
• Osteoporosis: Glucocorticoids can cause a rapid decline in bone strength, leading to secondary osteoporosis in about 30-50% of chronic users 7.

Patient-Specific Risks

The risk of steroid-related complications may vary depending on the individual patient and their specific condition. For example:

• Patients with Cushing syndrome or bilateral adrenal disease may require lifelong steroid replacement therapy and are at higher risk of complications 8.
• Patients undergoing unilateral adrenalectomy for non-Cushing adrenal disease may not require steroid replacement therapy and are at lower risk of complications 8.
• The dose and duration of steroid replacement therapy can also impact the risk of complications, with higher doses and longer durations associated with increased risk 4, 5.