Corticosteroids & Adrenal Insufficiency: Hospitalisation Risk

The long-term use of systemic corticosteroids, medications used to reduce inflammation, is linked to an increased risk of adrenal insufficiency and related hospitalizations. This finding, reported by Medscape News UK, underscores the importance of careful monitoring for patients on prolonged steroid therapy. Whereas the risk is most pronounced with systemic corticosteroids – those taken orally or intravenously – even long-term use of inhaled corticosteroids, commonly used for asthma and COPD, shows a more modest association with the condition.

Understanding Adrenal Insufficiency

Adrenal insufficiency, similarly known as adrenal failure, occurs when the adrenal glands don’t produce enough cortisol. Cortisol is a vital hormone that helps the body respond to stress, regulates metabolism, maintains blood pressure, and controls inflammation. When the adrenal glands are suppressed by external sources of corticosteroids, they can struggle to resume normal function, particularly after prolonged use. This suppression of the hypothalamic-pituitary-adrenal (HPA) axis, as described in the European Society of Endocrinology and Endocrine Society Joint Clinical Guideline, is an inevitable consequence of chronic exogenous glucocorticoid therapy.

The severity of adrenal insufficiency can range from mild fatigue and weakness to a life-threatening adrenal crisis. Symptoms can include chronic fatigue, muscle weakness, weight loss, decreased appetite, nausea, vomiting, and low blood pressure. An adrenal crisis is a medical emergency requiring immediate treatment with intravenous fluids and corticosteroids.

Who is at Risk?

The risk of developing adrenal insufficiency is directly related to the dose and duration of corticosteroid use. According to the clinical practice guideline, glucocorticoid exposure that poses a risk for adrenal insufficiency is expected to exceed a duration of 3-4 weeks or a daily hydrocortisone equivalent of 15-25 mg (roughly 4-6 mg of prednisone or prednisolone). At least 1% of the population uses chronic glucocorticoids as anti-inflammatory or immunosuppressive agents, meaning a significant number of individuals could be potentially affected. This includes people with conditions like rheumatoid arthritis, lupus, inflammatory bowel disease, and certain types of cancer, as well as those receiving organ transplants.

It’s important to note that the risk isn’t limited to high doses. Even low-dose glucocorticoid use (prednisone 2.5–7.5 mg/day) has been linked to increased risks of cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, fractures, and increased overall mortality, particularly in individuals with concurrent type 2 diabetes mellitus.

The Challenge of Diagnosis and Management

Diagnosing adrenal insufficiency can be complex, particularly in hospitalized patients. A study published in PubMed highlights that relative adrenal insufficiency is the most common cause of low cortisol levels in ill patients, and both cortisol and synthetic ACTH challenge assays can be unreliable in critically ill individuals. The study suggests that hydrocortisone should be the preferred steroid for most patients with relative adrenal insufficiency, with fludrocortisone considered on a case-by-case basis for those with refractory shock.

The European Society of Endocrinology and Endocrine Society guideline provides clinicians with practical guidance on evaluating adrenal function in adults on long-term steroid therapy and for supplementation therapy if adrenal insufficiency develops. Yet, the guideline also acknowledges the variability in recovery of adrenal function among individuals, making personalized assessment crucial.

Beyond Steroids: Other Causes of Adrenal Insufficiency

While this discussion focuses on glucocorticoid-induced adrenal insufficiency, it’s important to remember that other causes exist. Primary adrenal insufficiency, such as Addison’s disease, results from direct damage to the adrenal glands, often due to an autoimmune reaction. Secondary adrenal insufficiency occurs when the pituitary gland doesn’t produce enough adrenocorticotropic hormone (ACTH), which signals the adrenal glands to produce cortisol. These conditions require different diagnostic approaches and treatment strategies.

What Does This Mean for Patients?

If you are taking corticosteroids long-term, it is crucial to discuss the potential risks and benefits with your doctor. Do not stop taking your medication without medical advice, as abrupt cessation can also lead to adrenal insufficiency. Your doctor may recommend periodic monitoring of your adrenal function, especially if you are planning to discontinue steroid therapy. Be aware of the symptoms of adrenal insufficiency and seek medical attention if you experience any concerning signs.

Guidance Updates and Ongoing Research

The clinical practice guideline from the European Society of Endocrinology and Endocrine Society, published in June 2024, represents the most current consensus on the diagnosis and management of glucocorticoid-induced adrenal insufficiency. This guideline is expected to be reviewed and updated periodically as new evidence emerges. Further research is needed to better understand the long-term effects of steroid therapy on adrenal function and to develop more effective strategies for preventing and treating adrenal insufficiency. Hospital physicians are continuing to evaluate the use of steroids in patients with septic shock and hypocortisolemia, seeking to refine treatment protocols and improve patient outcomes.