medwireNews: The European Society of Endocrinology and the Endocrine Society have published a joint guideline on glucocorticoid-induced adrenal insufficiency (AI) that is designed to help clinicians manage patients who have or are at risk for developing the condition.
It is the first joint clinical practice guideline developed by the two societies and is published in their respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism. The recommendations were also presented at the European Congress of Endocrinology 2024 in Stockholm, Sweden.
Felix Beuschlein (University of Zürich, Switzerland) and co-authors explain that glucocorticoid therapy is widespread and is applied by most medical disciplines, often for a prolonged duration. Treatment can lead to glucocorticoid-induced AI, which requires careful education and management and, in the rare cases of adrenal crisis, prompt diagnosis and therapy.
In addition, patients can develop glucocorticoid withdrawal syndrome while tapering glucocorticoids within the supraphysiologic dose range, which has similar clinical features to those of AI. However, the authors note that AI symptoms are much more likely to develop when the overall total daily glucocorticoid dose is below physiologic levels, or at levels required for an adequate stress response.
The guideline begins with general recommendations for glucocorticoid therapy of non-endocrine conditions and advises that patients in this category do not need to be evaluated by an endocrinologist, but they should be educated about various endocrine aspects of glucocorticoid therapy, particularly the risk for AI for patients tapering glucocorticoid medication below the physiologic daily dose equivalent.
Taper of systemic glucocorticoid therapy for non-endocrine conditions is unnecessary for patients on short-term glucocorticoid therapy of less 3–4 weeks, irrespective of the dose, and treatment can be stopped without testing for hypothalamic–pituitary–adrenal (HPA) axis suppression.
For patients on long-term glucocorticoid therapy, taper should only be attempted if the underlying disease for which glucocorticoids were prescribed is controlled. The guidelines provide a table with a suggested tapering regimen according to the patient’s current daily glucocorticoid dose.
Clinicians should consider the possibility of glucocorticoid withdrawal syndrome during tapering. For severe symptoms, the authors recommend increasing the dose to the most recent tolerated level and lengthening the taper duration.
They do not recommend routine testing for AI in patients on supraphysiologic doses of glucocorticoids, as suppression of the HPA axis is expected at this level.
Clinicians should be particularly aware of the possibility for glucocorticoid-induced AI among current or recent users of:
- Non-oral glucocorticoid formulations who present with AI symptoms
- Multiple glucocorticoid formulations
- High-dose inhaled or topical glucocorticoids
- Inhaled or topical glucocorticoids for more than 1 year
- Intra-articular glucocorticoid injections
- Concomitant P450 3A4 inhibitors
The authors recommend morning cortisol testing for suspected AI in patients tapering or stopping glucocorticoid therapy and dynamic testing when the result is indeterminate.
They also suggest that patients with a history of glucocorticoid use presenting with symptoms of exogenous Cushing’s syndrome should be assumed to have glucocorticoid-induced AI.
The guideline recommends referral to an endocrinologist for patients who aim to discontinue glucocorticoids but have not had HPA axis recovery during a year on physiologic daily dose equivalent and for those with a history of adrenal crisis.
There are three recommendations related to stress dosing, supported by a chart with suggested glucocorticoid doses for patients at risk for or diagnosed with glucocorticoid-induced AI who are experiencing: minor stress, such as minor illness or infection; moderate to major stress, including severe acute illness, such as prolonged vomiting or diarrhea, and no signs of hemodynamic instability; or suspected adrenal crisis.
Finally, the document recommends that a diagnosis of adrenal crisis should be considered, irrespective of the glucocorticoid type, mode of administration, and dose in patients who are currently taking or have recently taken glucocorticoids and present with hemodynamic instability, vomiting or diarrhea, and have not undergone biochemical testing to rule out glucocorticoid-induced AI.
The recommended treatment for patients with suspected adrenal crisis is parenteral glucocorticoids and fluid resuscitation.
Beuschlein and co-authors note that the evidence for most recommendations “is low or very low.” They therefore conclude that “future epidemiology research needs to define the true risk of clinical adrenal crisis and adrenal insufficiency.”
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European Journal of Endocrinology 2024; 5: G25–G51
The Journal of Clinical Endocrinology & Metabolism 2024; doi:10.1210/clinem/dgae250
European Congress of Endocrinology 2024, Stockholm, Sweden, May 11–14.