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
...nagement
...Recommendations for Glucocorticoid Therapy of...
...n 1.1We recommend that, in general, patients on,...
...dation 1.2We recommend that clinicians wh...
....3We recommend that patients on glu...
...ommendations Regarding Taper of Systemic...
...ation 2.1We suggest not to taper glucocor...
...ndation 2.2Glucocorticoid taper for patient...
...on 2.3We recommend consideration of glucocorticoid...
...commendation 2.4We recommend against routine...
...dation 2.5We suggest that patients taking long-act...
...ndation 2.6We suggest that patients on a physiolog...
....7If confirmation of recovery of the HPA axis is d...
...ndation 2.8We suggest against routinely perfor...
....9We suggest awareness of possible glucocort...
...ecommendation 2.10We suggest that pa...
Recommendation 2.11We suggest that pa...
...n 2.12We recommend against the use...
...Recommendations on Diagnosis and Th...
...n 3.1We recommend that patients with cur...
...tion 3.2We suggest that in patients wi...
...ure 1. Schematic Representation of HP...
...osed Approach to Systemic Glucocorticoid Disco...
...3. Management of Patients at Risk of o...
...rmacologic Characteristics of Commonly Pre...
...verview of Topics Prescribing Clinicians Should...
...3. Risk Factors for Developing Adrenal Insu...
...sted Tapering Regimen Depending on Glucocortico...
...nical Features of Adrenal Insufficiency, Glucoc...
...ral Glucocorticoid Formulations and Risk of Gluco...
...gns and Symptoms of Glucocorticoid-induced (Exogen...
...able 8. Suggested Glucocorticoid R...
...inor stress...
...considerationsIf the patient is already tak...
...xample Illness requiring bed res...
...Minor surgery including any procedure requiring...
...el procedures not carried out under general a...
Moderate and major str...
...l considerationsIf the patient is already taking...
...vere intercurrent illness, for example:...
...Surgery or any procedure requiring general or r...
...ry (including cesarean section) or any proced...
...and vaginal delivery Suggested regimen...
.... Signs and Symptoms of Adrenal Crisis and Potent...