Glucocorticoid-Induced Adrenal Insufficiency

Publication Date: May 10, 2024

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

Managem...

...al Recommendations for Glucocorticoid Therapy...

...ion 1.1We recommend that, in general,...

...ion 1.2We recommend that clinician...

...ion 1.3We recommend that patients on glucocorticoi...


...ndations Regarding  Taper of Syst...

...n 2.1We suggest not to taper glucocorticoids i...

...commendation 2.2Glucocorticoid taper for p...

...ecommendation 2.3We recommend consideration of g...

...ation 2.4We recommend against routine testing f...

...ecommendation 2.5We suggest that patie...

...ndation 2.6We suggest that patients on a physio...

...ion 2.7If confirmation of recovery...

...2.8We suggest against routinely per...

Recommendation 2.9We suggest awareness of po...

...mendation 2.10We suggest that patien...

...commendation 2.11We suggest that patie...

...ndation 2.12We recommend against the u...


...commendations on Diagnosis and Therapy...

...3.1We recommend that patients with current or rec...

...mmendation 3.2We suggest that in patient...


...ure 1. Schematic Representation of HPA Axis R...


...roposed Approach to Systemic Glucocor...


...ure 3. Management of Patients at Risk of...


.... Pharmacologic Characteristics of Commo...


...ble 2. Overview of Topics Prescribing Clin...


...actors for Developing Adrenal Insufficiency,...


...Suggested Tapering Regimen Depending on Glu...


...le 5. Clinical Features of Adrenal Insufficienc...


...l Glucocorticoid Formulations and Risk of G...


...and Symptoms of Glucocorticoid-induced...


...ble 8. Suggested Glucocorticoid Regimens in...

...nor stre...

...eneral considerationsIf the patient is alre...

...Illness requiring bed rest Illness w...

...Minor surgery including any procedure requirin...

...Bowel procedures not carried out...

...derate and major stress...

...siderationsIf the patient is already...

...evere intercurrent illness, for exa...

...e Surgery or any procedure requir...

...Surgery (including cesarean section) or a...

...ample Labor and vaginal delivery...


...e 9. Signs and Symptoms of Adrenal Crisis and P...