Olaf Dekkers highlights this new European Society of Endocrinology (ESE) and Endocrine Society (ES) Joint Clinical Guideline,¹ the first of many future collaborations

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory and immunosuppressive agents. It is estimated that at least 1% of the adult population is on chronic GC therapy.² As exogenous GCs suppress the hypothalamus−pituitary−adrenal (HPA) axis, this population is potentially at risk for GC-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the GC, the route of administration and individual susceptibility.³ The recently published guideline, a joint effort of the ESE and the ES, aims to provide advice regarding diagnosis and therapy of GC-induced adrenal insufficiency.¹ Considering the widespread use of GCs and the risk of GC-induced adrenal insufficiency, the guidance will support not only endocrinology specialists, but also other specialists involved in the care of these patients.

Developing the guideline

To create the guideline, we performed systematic reviews to guide the recommendations. The reviews considered the incidence of recovery of the HPA axis after GC-induced adrenal insufficiency, the optimal tapering scheme for GCs in patients no longer in need of these drugs for the underlying condition, and the diagnostic accuracy of biochemical testing for adrenal insufficiency in GC users. Taking into account the high prevalence of GC use, the evidence was (surprisingly) limited. Most papers on biochemical testing did not relate the data to clinical symptoms compatible with adrenal insufficiency or adrenal crisis. We also did not find good evidence for the optimal tapering scheme in GC users. However, there was no clear evidence that patients who were tapering were at serious risk for adrenal crisis.¹

Clinical management

The guideline recommends that, in general, patients on or tapering off GCs for non-endocrine conditions do not need to be evaluated by an endocrinology specialist. However, these patients should be informed about various endocrine aspects of their GC therapy. This includes iatrogenic Cushing’s, adrenal insufficiency and GC withdrawal syndrome.

Tapering

When considering tapering, two types of tapering should be distinguished:

• tapering of GC therapy dose guided by the status of the underlying disease (=therapeutic tapering)
• tapering guided by the management of GC withdrawal and (prevention of) adrenal insufficiency (=endocrine tapering).

It should be emphasised that the evidence behind the recommendations on tapering is weak, and that individual patient characteristics and patient preferences need to be taken into account.

The guideline suggests not to taper GCs in patients on short term GC therapy of less than 3−4 weeks, irrespective of the dose. In these cases, GCs can be stopped without testing, due to low concern for HPA axis suppression. Endocrine tapering should only be attempted if the underlying disease no longer needs GC therapy. In these cases, GCs are tapered until the physiologic daily dose equivalent is approached (e.g. 4−6mg prednisone). In general, tapering of GCs can be more rapid within a supraphysiological range, followed by a slower taper when GC dosing is physiological.

GC withdrawal syndrome should be taken into consideration as it may occur during GC tapering. When GC withdrawal syndrome is severe, the GC dose can be temporarily increased to the most recent one that was tolerated, and the duration of GC tapering could be increased.

Measuring HPA axis function

The central question is how to determine the adequate functioning of the HPA axis. Again, there is no firm evidence that can guide the optimal strategy. The guideline proposes two approaches: a) continue to gradually taper the GC dose, while clinically monitoring for signs and symptoms of adrenal insufficiency, or b) test using a morning serum cortisol (see the guideline for discussion of the cut-offs¹ ). We suggest against routinely performing a dynamic test for diagnosing adrenal insufficiency in patients who are tapering or stopping GC therapy, as morning cortisol measurement can serve as a simple approach to HPA axis assessment, obviating the need for other tests in many individuals.

Emergency situations

In patients with current or recent GC use, who have not undergone biochemical testing to rule out GC-induced adrenal insufficiency and who present with haemodynamic instability, vomiting or diarrhoea, the guideline suggests that the diagnosis of adrenal crisis should be considered, irrespective of the GC type, mode of administration and dose. Patients with suspected adrenal crisis should be treated with parenteral GC and fluid resuscitation.

References

1. Beuschlein, Else et al. 2024 European Journal of Endocrinology https://doi.org/10.1093/ejendo/lvae029 and Journal of Clinical Endocrinology & Metabolism https://doi.org/10.1210/clinem/dgae250
2. Fardet et al. 2011 Rheumatology https://doi.org/10.1093/rheumatology/ker017.
3. Broersen et al. 2015 Journal of Clinical Endocrinology & Metabolism https://doi.org/10.1210/jc.2015-1218

Supplementary information

• Patient Leaflet
• Emergency Card
• Presentation Slides from ECE 2024 in May, where the Guideline was presented
• Pocket Guide
• Video of a discussion between the Joint Guideline co-Chairs

Disclosures: This article was provided to touchENDOCRINOLOGY by the ESE. No fees or funding were associated with this short publication.