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

...anagement

...General Recommendations for Glucocorticoid Therap...

...1.1We recommend that, in general, patients on,...

...ation 1.2We recommend that clinicians...

...commendation 1.3We recommend that...


...tions Regarding  Taper of Systemic Gluc...

...dation 2.1We suggest not to taper glucocorticoids...

...endation 2.2Glucocorticoid taper for pa...

...ation 2.3We recommend consideration of glucocort...

...ommendation 2.4We recommend against routi...

...dation 2.5We suggest that patients taking...

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

...n 2.7If confirmation of recovery of the HPA axi...

Recommendation 2.8We suggest against...

...on 2.9We suggest awareness of possibl...

...tion 2.10We suggest that patients with current...

...n 2.11We suggest that patients aiming to d...

Recommendation 2.12We recommend against the use...


...endations on Diagnosis and Therapy of...

...ndation 3.1We recommend that patient...

...endation 3.2We suggest that in patients...


...matic Representation of HPA Axis Recovery...


...roposed Approach to Systemic Glucoco...


Figure 3. Management of Patients at Risk of...


...harmacologic Characteristics of Commonl...


...iew of Topics Prescribing Clinicians Shou...


Table 3. Risk Factors for Developing Adrenal...


...ggested Tapering Regimen Depending on...


...e 5. Clinical Features of Adrenal I...


...n-oral Glucocorticoid Formulations an...


...Signs and Symptoms of Glucocorticoid...


...gested Glucocorticoid Regimens in Patient...

...inor stres...

...considerationsIf the patient is alre...

Example Illness requiring bed rest Illne...

...mple Minor surgery including any pro...

...e Bowel procedures not carried out un...

...and major stress ...

...ral considerationsIf the patient is...

...le Severe intercurrent illness, for examp...

...gery or any procedure requiring general...

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

...Labor and vaginal delivery Suggested regi...


...and Symptoms of Adrenal Crisis and Pote...