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
...anagement...
...General Recommendations for Glucocorticoid Therap...
...mendation 1.1We recommend that, in general, patien...
...1.2We recommend that clinicians who implement trea...
...ndation 1.3We recommend that patients on glucocor...
...tions Regarding Taper of Systemic Glucoco...
...ecommendation 2.1We suggest not to taper glucoco...
...ation 2.2Glucocorticoid taper for patients on...
...commendation 2.3We recommend considerati...
...dation 2.4We recommend against rout...
...2.5We suggest that patients taking long-actin...
...endation 2.6We suggest that patients on a physio...
...ion 2.7If confirmation of recovery of the...
...dation 2.8We suggest against routinely perform...
...ecommendation 2.9We suggest awaren...
...endation 2.10We suggest that patients with...
...dation 2.11We suggest that patients...
...n 2.12We recommend against the use of fludroc...
...ecommendations on Diagnosis and Therapy of...
...ecommendation 3.1We recommend that patient...
...n 3.2We suggest that in patients w...
...re 1. Schematic Representation of HPA Axis Rec...
...posed Approach to Systemic Glucocorticoi...
...ure 3. Management of Patients at Risk o...
...1. Pharmacologic Characteristics of Commonly P...
...view of Topics Prescribing Clinicians Should Discu...
...le 3. Risk Factors for Developing Adrenal...
Table 4. Suggested Tapering Regimen De...
...5. Clinical Features of Adrenal Insuffi...
...n-oral Glucocorticoid Formulations and Ri...
...Signs and Symptoms of Glucocorticoid-ind...
...gested Glucocorticoid Regimens in Patient...
Minor stres...
...eneral considerationsIf the patient is alr...
...Illness requiring bed rest Illness with...
Example Minor surgery including any pr...
...Bowel procedures not carried out...
...e and major stress ...
...al considerationsIf the patient is already ta...
...xample Severe intercurrent illness, for exampl...
...Surgery or any procedure requiri...
...ery (including cesarean section) or any procedure...
...ample Labor and vaginal delivery...
...nd Symptoms of Adrenal Crisis and Pote...