Long-Term Use of Oral and Inhaled Steroids Associated with Adrenal Insufficiency: Insights from Real-World Evidence

Long-term corticosteroid treatments markedly increase risk of adrenal insufficiency, new study reveals

Recent research presented at the upcoming Joint Congress of the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) sheds compelling light on the considerable risks associated with prolonged corticosteroid therapy. The large-scale study focuses on individuals undergoing treatment with steroid tablets or inhaled corticosteroids for extended durations, revealing a significantly heightened likelihood of adrenal insufficiency—a potentially life-threatening condition stemming from adrenal gland failure to produce adequate cortisol.

Steroids, medically classified as corticosteroids, are widely utilized for their potent anti-inflammatory and immunosuppressive properties. They play a critical role in managing a wide spectrum of chronic diseases, ranging from respiratory ailments such as asthma and chronic obstructive pulmonary disease (COPD), to autoimmune disorders like rheumatoid arthritis and allergic reactions. Despite their therapeutic advantages, corticosteroids are a double-edged sword, carrying a risk profile that demands meticulous consideration, especially when used continuously.

The research team, led by Dr. Patricia Vaduva from Rennes University Hospital in France, conducted an extensive analysis involving over half a million individuals taking corticosteroids either orally or via inhalation for periods between three months and five years. Their findings were unequivocal: patients on steroid tablets for more than three months were more than sixfold likelier to be diagnosed with adrenal insufficiency compared to those treated exclusively with non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, this subgroup faced over three times the risk of hospitalization due to adrenal crisis, underscoring the severity of long-term steroid supplementation.

Intriguingly, the data also revealed that inhaled corticosteroids, traditionally considered safer regarding systemic effects, were not devoid of risk. Individuals using these inhaled forms exhibited a 55% increased risk of developing adrenal insufficiency. Crucially, however, this did not translate to a higher rate of hospital admissions, suggesting a potentially milder clinical course or more subtle biochemical suppression in these cases.

Adrenal insufficiency occurs when the adrenal cortex fails to generate sufficient cortisol, a vital glucocorticoid hormone essential for regulating metabolism, immune response, and stress adaptation. Chronic corticosteroid therapy exerts negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis, suppressing endogenous cortisol production. Over time, this suppression can drive the adrenal glands into a dormant or ‘sleep-like’ state. Abrupt cessation of steroid therapy in such scenarios precipitates a dangerous cortisol deficit, potentially triggering adrenal crisis—a rapid and life-threatening decline characterized by hypotension, electrolyte disturbances, and shock.

This study stands out as the most comprehensive real-world investigation examining the correlation between long-term corticosteroid use and adrenal insufficiency, encompassing both oral and inhaled formulations. Previous research had largely focused on pituitary suppression and cortisol dynamics but lacked robust clinical data on incidence rates of adrenal insufficiency in large patient cohorts under chronic steroid therapy.

Dr. Vaduva emphasizes the clinical implications: “Even low doses of inhaled corticosteroids, once considered relatively benign regarding systemic effects, have demonstrable potential to induce adrenal insufficiency. This challenges current perceptions and highlights the necessity of heightened vigilance within the medical community.” This insight calls for reconsideration of steroid dosing strategies and stresses the importance of patient education on risks associated with both oral and inhaled corticosteroids.

The therapeutic challenge lies in balancing effective disease management with minimizing adverse metabolic and endocrine sequelae. When long-term corticosteroid treatment is warranted, the study advocates for careful dose tapering rather than abrupt discontinuation to prevent withdrawal syndrome and adrenal insufficiency. Moreover, substitutive therapy with naturally occurring steroids like hydrocortisone should be adopted in clinical practice to support adrenal function during and after cessation, thereby reducing morbidity and hospitalization rates.

Beyond clinical management, the findings raise important questions about monitoring practices for patients on prolonged steroid therapy. Routine assessment of adrenal function and cortisol levels may be necessary even in patients receiving inhaled steroids, urging clinicians to adopt a more proactive surveillance approach. Current guidelines might require updating to incorporate these insights, fostering safer steroid use paradigms in both hospital and outpatient settings.

The data also hint at a broader public health concern. Steroid medications are prescribed extensively worldwide, and under-recognition of adrenal insufficiency risks could lead to preventable complications. Educational initiatives targeting healthcare professionals and patients alike are imperative to improve awareness, promote adherence to tapering regimens, and ensure timely intervention when symptoms of adrenal suppression arise.

This research contributes to an evolving understanding of the endocrinological impact of corticosteroids. It underscores the delicate interplay between synthetic hormone administration and the body’s intrinsic regulatory mechanisms. Corticosteroid therapy remains indispensable in modern medicine; however, this study calls for a recalibrated perspective on risk assessment, guided by quantitative evidence and centered on patient safety.

As the Joint Congress of ESPE and ESE convenes in Copenhagen in May 2025, these findings promise to stimulate in-depth discussions and potentially shape future clinical guidelines. Their significance resonates not only within endocrinology but across a vast array of medical specialties relying on corticosteroids as cornerstone treatments.

In conclusion, this landmark study elucidates the profound endocrine consequences of chronic corticosteroid use, emphasizing a pressing need for comprehensive management strategies that safeguard adrenal integrity. By highlighting the risks associated with both oral and inhaled corticosteroids, it bridges a critical knowledge gap and equips clinicians with data to inform safer therapeutic choices, ultimately enhancing patient outcomes.

Subject of Research: Impact of long-term corticosteroid therapy on adrenal insufficiency incidence and hospitalization risk

Article Title: Long-term corticosteroid therapy significantly elevates risk of adrenal insufficiency: insights from the largest real-world study

News Publication Date: Prior to Joint Congress of ESPE and ESE, May 2025

Web References: https://mediasvc.eurekalert.org/Api/v1/Multimedia/dd1f5150-c0b2-448c-b18c-8abc9d5a83e0/Rendition/low-res/Content/Public

Image Credits: European Society of Endocrinology

Keywords: Corticosteroids, Steroid hormones, Cortisol, Steroids, Organic compounds, Hospitals, Medical facilities, Patient monitoring, Respiratory disorders, Asthma, Chronic obstructive pulmonary disease, Health care, Medications, Drug safety, Antiinflammatory drugs, Side effects, Diseases and disorders, Endocrinology, Hormones, Endocrine glands, Adrenal glands

Tags: adrenal insufficiency riskautoimmune disorder managementchronic disease managementcorticosteroid side effectscorticosteroid therapy complicationscortisol production impairmentlong-term corticosteroid useoral and inhaled steroidspatient safety in steroid usepediatric endocrinology insightsreal-world evidence studyrespiratory disease treatment