Glucocorticoid-Induced Adrenal Insufficiency
Key Points
Key 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).
Definitions
- Physiologic daily dose equivalent: Daily glucocorticoid dose equivalent to average daily cortisol production (15–25 mg hydrocortisone, 4–6 mg prednisone or prednisolone, 3–5 mg methylprednisone, 0.25–0.5 mg dexamethasone). Endogenous production of cortisol is estimated to be 9–10 mg/day. The above mentioned doses are based on an estimate of bioavailability.
- Supraphysiologic glucocorticoid therapy: Any dose greater than physiologic daily dose equivalent (see above).
- Short-term glucocorticoid therapy: Any glucocorticoid therapy of less than 3–4 weeks duration.
- Long-term glucocorticoid therapy: Glucocorticoid therapy greater than 3–4 weeks duration with glucocorticoid doses greater than physiologic daily dose equivalent of hydrocortisone (15–25 mg hydrocortisone, 4–6 mg prednisone or prednisolone, 3–5 mg methylprednisone, 0.25–0.5 mg dexamethasone).
- Glucocorticoid taper: Taper of glucocorticoid therapy dose, initially guided by the management of the underlying disease (= therapeutic taper), and later by the management of glucocorticoid withdrawal and adrenal insufficiency (= endocrine taper).
- Glucocorticoid withdrawal syndrome: Symptoms experienced when lowering glucocorticoid dose within the supraphysiologic glucocorticoid dose range, that are not due to the underlying disease for which the glucocorticoids were initially prescribed for and per definition not due to untreated adrenal insufficiency, as the total glucocorticoid daily dose is still supraphysiologic.
Management
...agement...
...ral Recommendations for Glucocortico...
...ommendation 1.1We recommend that, in genera...
Recommendation 1.2We recommend that c...
...tion 1.3We recommend that patients on glucocor...
1.2 Recommendations Regarding Tap...
Recommendation 2.1We suggest not to taper g...
...ecommendation 2.2Glucocorticoid ta...
...mmendation 2.3We recommend consider...
...ecommendation 2.4We recommend against routine...
...ndation 2.5We suggest that patients taking lon...
...ndation 2.6We suggest that patients...
....7If confirmation of recovery of the HPA axis...
...n 2.8We suggest against routinely performing a dyn...
...dation 2.9We suggest awareness of possible...
...tion 2.10We suggest that patients with...
...2.11We suggest that patients aiming to disc...
...dation 2.12We recommend against the use of fludr...
...3 Recommendations on Diagnosis and Therapy o...
Recommendation 3.1We recommend that patients w...
...on 3.2We suggest that in patients w...
...igure 1. Schematic Representation...
...Proposed Approach to Systemic Glucoco...
...anagement of Patients at Risk of o...
...harmacologic Characteristics of Comm...
Table 2. Overview of Topics Prescribing Clinici...
...Factors for Developing Adrenal Insufficiency, an...
...le 4. Suggested Tapering Regimen Depending on Glu...
.... Clinical Features of Adrenal Insufficiency...
...ble 6. Non-oral Glucocorticoid Formulations...
...7. Signs and Symptoms of Glucocorticoid-...
...ggested Glucocorticoid Regimens in Patients at...
...r stress...
...erationsIf the patient is already taking hydrocor...
...Illness requiring bed rest Illness with fe...
...ample Minor surgery including any procedu...
...owel procedures not carried out under general an...
...e and major stress ...
...eneral considerationsIf the patient is a...
...Severe intercurrent illness, fo...
...e Surgery or any procedure requiri...
Example Surgery (including cesare...
...Labor and vaginal delivery Suggested reg...
...ble 9. Signs and Symptoms of Adrenal Crisis and...