Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency
1.1 General Recommendations for Glucocorticoid Therapy of Non-Endocrine Conditions and Recommendations Regarding Patient Education
Recommendation 1.1
We recommend that, in general, patients on, or tapering off glucocorticoids for non-endocrine conditions do not need to be evaluated by an endocrinology specialist.
()Recommendation 1.2
Recommendation 1.3
We recommend that patients on glucocorticoid therapy have access to current up-to-date and appropriate information about different endocrine aspects of glucocorticoid therapy.
( UGPS )1.2 Recommendations Regarding Taper of Systemic Glucocorticoid Therapy for Non-Endocrine Conditions, Diagnosis and Approach to Glucocorticoid-Induced Adrenal Insufficiency, and Glucocorticoid Withdrawal Syndrome
Recommendation 2.1
We suggest not to taper glucocorticoids in patients on short-term glucocorticoid therapy of <3-4 weeks, irrespective of the dose. In these cases, glucocorticoids can be stopped without testing due to low concern for HPA axis suppression.
( 2-VL )Recommendation 2.2
Glucocorticoid taper for patients on long-term glucocorticoid therapy should only be attempted if the underlying disease for which glucocorticoids were prescribed is controlled, and glucocorticoids are no longer required. In these cases, glucocorticoids are tapered until approaching the physiologic daily dose equivalent is achieved (eg, 4-6 mg prednisone).
( UGPS )Recommendation 2.3
We recommend consideration of glucocorticoid withdrawal syndrome that may occur during glucocorticoid taper. When glucocorticoid withdrawal syndrome is severe, glucocorticoid dose can be temporarily increased to the most recent one that was tolerated, and the duration of glucocorticoid taper could be increased.
( UGPS )Recommendation 2.4
We recommend against routine testing for adrenal insufficiency in patients on supraphysiologic doses of glucocorticoids, or if they are still in need of glucocorticoid treatment for the underlying disease.
( UGPS )Recommendation 2.5
We suggest that patients taking long-acting glucocorticoids (eg, dexamethasone or betamethasone) should be switched to shorter-acting glucocorticoids (eg, hydrocortisone or prednisone) when long-acting glucocorticoids are no longer needed.
( 2-VL )Recommendation 2.6
1. continue to gradually taper the glucocorticoid dose, while being monitored clinically for signs and symptoms of adrenal insufficiency, or
2. be tested with a morning serum cortisol. ( 2-VL )
Recommendation 2.7
If confirmation of recovery of the HPA axis is desired, we recommend morning serum cortisol as the first test. The value of morning serum cortisol should be considered as a continuum, with higher values more indicative of HPA axis recovery.
( 1-VL )As a guide:
1. we suggest that the test indicates recovery of the HPA axis if cortisol is >300 nmol/L or 10 μg/dL and glucocorticoids can be stopped safely;
2. we suggest that if the result is between 150 nmol/L or 5 μg/dL and 300 nmol/L or 10 μg/dL, the physiologic glucocorticoid dose should be continued, and the morning cortisol repeated after an appropriate time period (usually weeks to months);
3. we suggest that if the result is <150 nmol/L or 5 μg/dL, the physiologic glucocorticoid dose should be continued, and the morning cortisol repeated after a few months.
Recommendation 2.8
We suggest against routinely performing a dynamic test for diagnosing adrenal insufficiency in patients tapering or stopping glucocorticoid therapy.
( 2-VL )Recommendation 2.9
We suggest awareness of possible glucocorticoid-induced adrenal insufficiency in patients:
1. with current or recent use of non-oral glucocorticoid formulations presenting with signs and symptoms indicative of adrenal insufficiency, or
2. using multiple glucocorticoid formulations simultaneously, or
3. using high-dose inhaled or topical glucocorticoids, or
4. using inhaled or topical glucocorticoids for >1 year, or
5. who received intra-articular glucocorticoid injections in the previous 2 months, or
6. receiving concomitant treatment with strong cytochrome P450 3A4 inhibitors.
Recommendation 2.10
Recommendation 2.11
We suggest that patients aiming to discontinue glucocorticoids, but without recovery of HPA axis in one year while on physiologic daily dose equivalent, should be evaluated by an endocrinology specialist. We suggest that patients on glucocorticoids and history of adrenal crisis should also be evaluated by an endocrinology specialist.
( UGPS )Recommendation 2.12
1.3 Recommendations on Diagnosis and Therapy of Adrenal Crisis in Patients With Glucocorticoid-induced Adrenal Insufficiency
Recommendation 3.1
We recommend that patients with current or recent glucocorticoid use who did not undergo biochemical testing to rule out glucocorticoid-induced adrenal insufficiency should receive stress dose coverage when they are exposed to stress.
Recommendation 3.1A
- Oral glucocorticoids should be used in case of minor stress and when there are no signs of hemodynamic instability or prolonged vomiting or diarrhea.
Recommendation 3.1B
- Parenteral glucocorticoids should be used in case of moderate to major stress, procedures under general or regional anesthesia, procedures requiring prolonged avoidance or inability of oral intake, or when there are signs of hemodynamic instability or prolonged vomiting or diarrhea.
Recommendation 3.2
We suggest that in patients with current or recent glucocorticoid use who did not undergo biochemical testing to rule out glucocorticoid-induced adrenal insufficiency and present with hemodynamic instability, vomiting, or diarrhea, the diagnosis of adrenal crisis should be considered irrespective of the glucocorticoid type, mode of administration, and dose; patients with suspected adrenal crisis should be treated with parenteral glucocorticoids and fluid resuscitation.
( UGPS )Recommendation Grading
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Overview
Title
Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency
Authoring Organizations
Endocrine Society
European Society of Endocrinology
Publication Month/Year
May 10, 2024
Last Updated Month/Year
May 29, 2024
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
Global
Document Objectives
Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Assessment and screening, Treatment, Management
Diseases/Conditions (MeSH)
D005938 - Glucocorticoids, D000309 - Adrenal Insufficiency
Keywords
glucocorticoids, adrenal insufficiency, adrenal crisis, steroids
Source Citation
Felix Beuschlein, Tobias Else, Irina Bancos, Stefanie Hahner, Oksana Hamidi, Leonie van Hulsteijn, Eystein S Husebye, Niki Karavitaki, Alessandro Prete, Anand Vaidya, Christine Yedinak, Olaf M Dekkers, European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae250, https://doi.org/10.1210/clinem/dgae250