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
....1 General Recommendations for Gluco...
...mendation 1.1We recommend that, in...
...ion 1.2We recommend that clinicians wh...
...1.3We recommend that patients on glucocortic...
...Recommendations Regarding Taper of S...
...2.1We suggest not to taper glucocorticoids i...
...ecommendation 2.2Glucocorticoid taper for patients...
...ion 2.3We recommend consideration of glucoc...
...ation 2.4We recommend against routine tes...
...mmendation 2.5We suggest that patients taking...
...2.6We suggest that patients on a physiologic...
...ndation 2.7If confirmation of recovery of...
...mmendation 2.8We suggest against routinely...
...2.9We suggest awareness of possible gl...
...on 2.10We suggest that patients with...
...on 2.11We suggest that patients aiming to d...
...dation 2.12We recommend against the use of flu...
...commendations on Diagnosis and Therapy of...
...endation 3.1We recommend that patients with...
...ion 3.2We suggest that in patients with curren...
.... Schematic Representation of HPA Axis Recovery...
...osed Approach to Systemic Glucocorticoid Discon...
...gement of Patients at Risk of or With Diagnosed...
...1. Pharmacologic Characteristics of Com...
...iew of Topics Prescribing Clinicians Should Discu...
.... Risk Factors for Developing Adrenal Insuffici...
...ed Tapering Regimen Depending on G...
...able 5. Clinical Features of Adrenal Ins...
...e 6. Non-oral Glucocorticoid Formulations and R...
...7. Signs and Symptoms of Glucocorticoid-induc...
...sted Glucocorticoid Regimens in Patients at Ris...
...r stress...
...al considerationsIf the patient is...
...Illness requiring bed rest Il...
...ample Minor surgery including any procedure...
...mple Bowel procedures not carried ou...
...erate and major st...
...nsiderationsIf the patient is alre...
...evere intercurrent illness, for example:...
...rgery or any procedure requiring general or reg...
...rgery (including cesarean section) or an...
...and vaginal delivery Suggeste...
...s and Symptoms of Adrenal Crisis and...