Long-term steroid use linked to adrenal gland impairment: real-world evidence

Treatment with steroid tablets for longer than three months has been shown to increase the likelihood of diagnosis with adrenal insufficiency (AI) by more than six times when compared with those treated with non-steroidal anti-inflammatory drugs (NSAIDs). It has also been found that these patients have a higher risk of hospitalisation for AI – also called Addison’s disease – but also that the long-term users of inhaled steroids have an increased risk of developing AI although without any increase in frequency of hospitalisation. 

These findings were presented at the first Joint Congress between the European Society of Endocrinology (ESE) and the European Society of Paediatric Endocrinology (ESPE) held in Copenhagen, in May 2025. This real-world evidence (RWE) highlights the need for alternative treatments – for example hydrocortisone – in order to prevent the AI disease.

Anti-inflammatory steroids – also called corticosteroids – are drugs used to treat conditions ranging from asthma, chronic obstructive pulmonary disease (COPD), allergies, arthritis and autoimmune disorders. When taking these medicines for longer than three weeks, – e.g., if prednisolone is used to treat a serious asthma exacerbation – the dose taken must be gradually reduced. Stopping abruptly can lead to the adrenal gland ceasing production of the stress hormone cortisol which is known as AI.

Dr Patricia Vaduva, and her research team from France, examined patient records in their study of more than half a million users of steroid tablets or inhaled steroids – from three months to five years – and compared them to individuals who were treated only with NSAIDs. 

The team saw that those who used steroid tablets three months or longer were more than six times more likely to be diagnosed with AI. Significantly, they were also more than three times more likely to be hospitalised for AI than those who only used NSAIDs. Similarly, a greater than 50% risk of AI diagnosis was seen in those who took inhaled steroids. This cohort however did not exhibit a higher risk of hospitalisation for AI.

“Our real-world study is the largest to investigate the association between long-term corticosteroid use and AI,” said Dr Vaduva from Rennes University Hospital, and lead author of the study.

“The impact of corticosteroids on the pituitary gland – which is located in the brain and regulates adrenal gland cortisol secretion – has been looked at previously, but studies on the incidence of AI following the chronic [long-term] use of both oral- and inhaled-corticosteroids [have been] lacking.”

“Our findings show that even low doses of inhaled steroids can lead to AI, contrary to what [has been] thought until now. This information should be [shared] widely across the medical community,” added Dr Vaduva.

“The presence of synthetic corticosteroids in the blood can cause the adrenal glands to go into a ‘sleep-like’ state, where they reduce or stop producing cortisol. 

“Therefore, when long-term corticosteroid therapy is stopped suddenly, a substitutive treatment with a naturally occurring steroid like hydrocortisone is needed to avoid AI and its potential life-threatening consequences. 

“This will allow patients to be safe and will prevent numerous hospitalisations,” concluded Dr Vaduva.

Abstract (as presented in Copenhagen)

Real-world incidence of adrenal insufficiency after long-term use of systemic and inhaled corticosteroids

AIM: The incidence of adrenal insufficiency following chronic use of both systemic and inhaled corticosteroids remains poorly known. The aim of our study was to assess the incidence of hospitalization for adrenal insufficiency (AI) after long-term use of systemic and inhaled corticosteroids in a large population-based cohort.

METHODS: We used TriNetx Research Collaborative network, with access to electronic medical records from a number of participating health care organizations, to identify participants. Diagnosis was done using the International Classification of Diseases codes, and data on medications were studied. We included individuals who were treated with long-term systemic or inhaled only corticosteroids. We excluded those with a past history of causes of primary and secondary adrenocortical insufficiency. We used a 1:1 propensity-score to compare matched subjects treated by long term systemic (n=243,430) or inhaled (n=315,237) steroid to subjects treated by NSAID only.

RESULTS: Mean age of the population studied was 56.5 ± 18 years, with 40% of men. Over a mean follow-up of 2.4 ± 1.9 years, long-term systemic corticosteroids use was associated with a more frequent diagnosis of AI (0.20% vs 0.04% per year; HR: 6.32, 95%CI [5.50-7.26], p<0.001) and a greater incidence of hospitalization for AI (0.02% vs 0.008% per year; HR: 3.52, 95%CI [2.57-4.84], p<0.001) as compared to individuals treated with NSAID. Long-term inhaled corticosteroids use was associated with a more common diagnosis of AI (0.05% vs 0.04% per year; HR: 1.55, 95%CI [1.34- 1.80], p<0.001), without increased risk of hospitalization for AI (0.01% vs 0.01% per year; HR: 1.26, 95%CI [0.91-1.76], p=0.17) as compared to NSAID therapy.

CONCLUSIONS: Long-term use of systemic corticosteroids was associated with an increased risk of diagnosed AI with a greater incidence of hospitalization for AI over a 2.4-year follow-up. Inhaled corticosteroids use was associated with an increased incidence of diagnosed AI. These findings from a large real world-based cohort underscore the importance of preventing the onset of corticotropic insufficiency among individuals with long-term corticosteroids treatment.