Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency

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.

We recommend that patients on glucocorticoid therapy have access to current up-to-date and appropriate information about different endocrine aspects of glucocorticoid therapy.

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.

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).

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.

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.

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.

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.

We suggest against routinely performing a dynamic test for diagnosing adrenal insufficiency in patients tapering or stopping glucocorticoid therapy.

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.

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.

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.

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.