Adrenal insufficiency, glucocorticoid-induced adrenal insufficiency, and glucocorticoid withdrawal syndrome
| Adrenal insufficiency | Glucocorticoid-induced adrenal insufficiency | Glucocorticoid withdrawal syndrome | |
|---|---|---|---|
| Diagnosis | Clinical symptoms and biochemical testing: Low 8 AM cortisol (< 4.8 μg/dL)a Abnormal response to corticotropin stimulation test (cortisol peak < 12.6 μg/dL at 30 minutes and 60 minutes)a Variable adrenocorticotropic hormone (for primary adrenal insufficiency > 63.3 pg/mL, for secondary adrenalinsufficiency < 7.2 pg/mL)b | After abrupt discontinuation or quick taper of exogenous glucocorticoid or Cushing syndrome: Low 8 AM cortisol (< 4.8 μg/dL)a Low adrenocorticotropic hormone (< 7.2 pg/mL)b Low dehydroepiandrosterone sulfatec Abnormal response to corticotropin stimulation test (cortisol peak < 12.6 μg/dL at 30 and 60 minutes)a | Clinical symptoms of adrenal insufficiency with or without cushingoid features while gradually tapering or after abrupt discontinuation of glucocorticoid No laboratory test to diagnose |
| Mechanism | Lack of glucocorticoid secretion from adrenal cortex due to either adrenal etiology (primary adrenal insufficiency) or pituitary or hypothalamic etiology (secondary adrenal insufficiency) | HPAA suppression due to excessive endogenous or exogenous glucocorticoid, leading to atrophy of adrenal cortex | Tolerance of and dependence on supraphysiologic doses of glucocorticoid |
| Prevention | Replace with physiologic doses of glucocorticoid | Gradually taper glucocorticoid until completely stopped | Use the lowest effective supraphysiologic glucocorticoid dose when indicated |
| Treatment | Replace with physiologic doses of glucocorticoid | Gradually taper glucocorticoid until completely stopped Consider stress-dose glucocorticoid under stressors | No effective treatment: empirically increase glucocorticoid to prolong HPAA suppression |
↵a Cortisol values per the Elecsys Cortisol II assay.
↵b Adrenocorticotropic hormone values per the Electro Chemiluminescence Immunoassay.
↵c Dehydroepiandrosterone sulfate normal values (μg/dL) per the Electro Chemiluminescence Immunoassay for females, by age:
15–19 years 65.1–368.0; 20–24 years 148–407; 25–34 years 98.8–340; 35–44 years 60.9–337; 45–54 years 35.4–256; 55–64 years 18.9–205; 65–74 years < 247; 75–99 years 12–154.
For males, by age:
15–19 years 70.2–492; 20–24 years 211–492; 25–34 years 160–449; 35–44 years 88.9–427; 45–54 years 44.3–331; 55–64 years 51.7–295; 65–74 years 33.6–249; 75–99 years 16.2–123.
HPAA = hypothalamic-pituitary-adrenal axis