Are patients on chronic steroid replacement therapy at increased risk of complications?

From the Guidelines

Yes, patients on chronic steroid replacement therapy are at increased risk of complications, including adrenal crisis, osteoporosis, increased susceptibility to infections, poor wound healing, glucose intolerance, hypertension, and electrolyte abnormalities. These complications occur because exogenous steroids suppress the hypothalamic-pituitary-adrenal axis, leading to adrenal atrophy and inability to increase endogenous cortisol production during stress 1. Additionally, chronic steroid exposure affects multiple body systems through prolonged glucocorticoid receptor activation, altering metabolism, immune function, and bone remodeling.

To mitigate these risks, patients require stress-dose steroids during illness or procedures (typically 2-3 times their maintenance dose), with hydrocortisone 100mg IV being common for major surgery or severe illness 1. Patients should wear medical alert identification and carry emergency hydrocortisone for self-administration. Regular monitoring of bone density, blood pressure, blood glucose, and electrolytes is essential. The lowest possible dose of steroids should be used for the shortest possible duration to minimize the harmful impact of steroids 1. Certain patients with pre-existing conditions like diabetes mellitus or an immune-compromised status and the elderly will need special attention.

Some of the potential complications of chronic steroid replacement therapy include:

• Adrenal crisis during times of stress, infection, or surgery
• Osteoporosis
• Increased susceptibility to infections
• Poor wound healing
• Glucose intolerance
• Hypertension
• Electrolyte abnormalities
• Cosmetic changes, such as facial rounding, dorsal hump formation, striae, weight gain, acne, alopecia, and facial hirsutism 1
• Severe side effects, including osteopenia with vertebral compression, brittle diabetes, psychosis, hypertension, and malignancy 1

It is crucial to evaluate the patient’s pre-existing conditions and carefully monitor steroid-related complications, using prophylactic agents to prevent certain opportunistic infections and preemptive measures to mitigate various toxicities 1. A multidisciplinary approach may be used in the management of certain steroid-related complications, and institutional guidelines should be considered in decision-making 1.

From the FDA Drug Label

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment Corticosteroids, including prednisone tablets, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens The rate of infectious complications increases with increasing corticosteroid dosages.

Patients on chronic steroid replacement therapy are at increased risk of complications, including:

• Infections
• Osteoporosis
• Adrenal insufficiency
• Cardiovascular complications
• Gastrointestinal complications
• Musculoskeletal complications
• Neuro-psychiatric complications
• Ophthalmic complications

This is because corticosteroids suppress the immune system and can cause a range of adverse effects, particularly with long-term use 2, 2. The risk of complications increases with the size of the dose and the duration of treatment 2. Therefore, the lowest possible dose of corticosteroids should be used to control the condition under treatment 2.

From the Research

Complications of Chronic Steroid Replacement Therapy

• Patients on chronic steroid replacement therapy are at increased risk of complications, including osteoporosis and fractures 3, 4, 5.
• The use of glucocorticoids can lead to a rapid decline in bone strength, particularly in the first 3-6 months of treatment, due to increased bone resorption and decreased bone formation 4.
• The risk of fracture is a major concern, with even low doses of glucocorticoids potentially increasing the risk of fragility fracture 5.
• Other potential complications of chronic steroid replacement therapy include:
  • Toxicity to articular cartilage 6
  • Systemic side effects, such as increases in blood glucose levels and a reduction in immune function 6
  • Increased risk of infections 6

Management of Complications

• Patients on chronic steroid replacement therapy should be counselled on lifestyle measures to maintain bone strength, including nutrition and weight-bearing exercise 4.
• Pharmacological therapy, such as oral bisphosphonates, may be considered for patients at moderate to high risk of fracture 4, 5.
• The use of glucocorticoids should be prescribed at the lowest dose and shortest duration necessary to minimize the risk of complications 4, 5.