Clinical Practice Guideline

Glucocorticoid-Induced Adrenal Insufficiency Guideline Resources

May 13, 2024

Full Guideline: European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency
JCEM | June 2024 (online May 2024)

Felix Beuschlein (Chair), Tobias Else (Co-Chair), Irina Bancos, Stefanie Hahner, Oksana Hamidi, Leonie van Hulsteijn, Eystein S Husebye, Niki Karavitaki, Alessandro Prete, Anand Vaidya, Christine Yedinak, Olaf M Dekkers (Methodologist)

This 2024 guideline is a joint guideline between the European Society of Endocrinology (ESE) and the Endocrine Society led by ESE

Resources

  • Guidelines Pocket Card | Guideline Central COMING SOON
  • Patient Resources | ESE Patient Zone COMING SOON

Essential Points

  • At least 1% of the population uses chronic glucocorticoids (GC) as anti-inflammatory or immunosuppressive agents
  • Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an inevitable effect of chronic exogenous glucocorticoid therapy, and recovery of adrenal function varies greatly amongst individuals.
  • Even low dose glucocorticoid use (prednisone 2.5–7.5 mg/day) increases risks of cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis and fractures, and increases overall mortality with concurrent type 2 diabetes mellitus.
  • Glucocorticoid exposure via oral administration that poses risk for adrenal insufficiency is expected to at least exceed both of the following thresholds:
  • Duration of glucocorticoid therapy to pose risk for adrenal insufficiency: 3–4 weeks or greater.
  • Dose of glucocorticoid therapy to pose risk for adrenal insufficiency: any dose greater than daily hydrocortisone equivalent of 15–25 mg (4–6 mg prednisone or prednisolone, 3–5 mg methylprednisone, 0.25–0.5 mg dexamethasone).

List of Recommendations

1.1 General recommendations for glucocorticoid therapy of non-endocrine conditions and recommendations regarding patient education

  • R 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.
  • R 1.2 We recommend that clinicians who implement treatment with glucocorticoids educate patients about various endocrine aspects of glucocorticoid therapy. (Good clinical practice)
  • R 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. (Good clinical practice)

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

  • R 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. (⊕○○○)
  • R 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 (e.g., 4-6 mg prednisone). (Good clinical practice)
  • R 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. (Good clinical practice)
  • R 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. (Good clinical practice)
  • R 2.5 We suggest that patients taking long-acting glucocorticoids (e.g., dexamethasone or betamethasone) should be switched to shorter-acting glucocorticoids (e.g., hydrocortisone or prednisone) when long-acting glucocorticoids are no longer needed. (⊕○○○)
  • R 2.6 We suggest that patients on a physiologic daily dose equivalent, and aiming to discontinue glucocorticoid therapy, either:
  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. (⊕○○○)
  • R 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. (⊕○○○)

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.
  • R 2.8 We suggest against routinely performing a dynamic test for diagnosing adrenal insufficiency in patients tapering or stopping glucocorticoid therapy. (⊕○○○)
  • R 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.
  • R 2.10 We suggest that patients with current or previous glucocorticoid treatment presenting with signs and symptoms of exogenous Cushing syndrome are assumed to have glucocorticoid-induced adrenal insufficiency. (Good clinical practice)
  • R 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. (Good clinical practice)
  • R 2.12 We recommend against the use of fludrocortisone in patients with glucocorticoid-induced adrenal insufficiency.

1.3. Recommendations on diagnosis and therapy of adrenal crisis in patients with glucocorticoid-induced adrenal insufficiency

  • R 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. (Good clinical practice)<
  • R3.1A Oral glucocorticoids should be used in case of minor stress and when there are no signs of hemodynamic instability or prolonged vomiting or diarrhea.
  • R3.1B 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.
  • R 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. (Good clinical practice)
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