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

Managemen...

....1 General Recommendations for Glucocorticoid Th...

...endation 1.1We recommend that, in general, pa...

...ndation 1.2We recommend that clinicians who implem...

...1.3We recommend that patients on glucocortico...


...2 Recommendations Regarding  Taper of S...

....1We suggest not to taper glucocorticoids in...

...ommendation 2.2Glucocorticoid taper for patie...

...mmendation 2.3We recommend consideration of...

...2.4We recommend against routine test...

Recommendation 2.5We suggest that patients takin...

...mendation 2.6We suggest that patients on a...

Recommendation 2.7If confirmation of recovery of t...

...mendation 2.8We suggest against routinely p...

...ommendation 2.9We suggest awareness of...

....10We suggest that patients with current or previ...

...dation 2.11We suggest that patients aiming to...

...n 2.12We recommend against the use o...


...commendations on Diagnosis and Thera...

...dation 3.1We recommend that patients with curre...

...commendation 3.2We suggest that in patients...


...gure 1. Schematic Representation of...


Figure 2. Proposed Approach to Systemic G...


...agement of Patients at Risk of or With Diagnosed...


...ble 1. Pharmacologic Characteristics of...


Table 2. Overview of Topics Prescribing Clinician...


.... Risk Factors for Developing Adrenal...


...ble 4. Suggested Tapering Regimen Depending on G...


...ical Features of Adrenal Insufficie...


...al Glucocorticoid Formulations and Risk...


...7. Signs and Symptoms of Glucocorticoi...


...le 8. Suggested Glucocorticoid Regimens...

...r stress

...al considerationsIf the patient is alrea...

...llness requiring bed rest Illness with fe...

...r surgery including any procedure...

...mple Bowel procedures not carried out u...

...oderate and major...

General considerationsIf the patient is already ta...

...re intercurrent illness, for example: P...

...ample Surgery or any procedure requiring general...

...gery (including cesarean section) or any pro...

...and vaginal delivery Suggested regi...


...nd Symptoms of Adrenal Crisis and Po...