Explain Why sudden withdrawal of glucocorticoids after prolong therapy is Contraindicated.
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glucocorticoid withdrawal AND adrenal insufficiency
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glucocorticoid withdrawal adrenal insufficiency tapering guideline endocrine society
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Sudden withdrawal of glucocorticoids after prolonged therapy is contraindicated because it may cause acute adrenal insufficiency, potentially an adrenal crisis.
Mechanism
Long-term exogenous glucocorticoids exert negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis:
Glucocorticoid treatment ↑
→ hypothalamic CRH ↓
→ pituitary ACTH ↓
→ adrenal cortisol production ↓ and adrenal cortex becomes atrophic.
→ hypothalamic CRH ↓
→ pituitary ACTH ↓
→ adrenal cortisol production ↓ and adrenal cortex becomes atrophic.
Thus, the body becomes dependent on the administered steroid. If it is stopped abruptly, the suppressed adrenal glands cannot immediately produce sufficient cortisol. Recovery may take weeks to months, and occasionally a year or longer. Goodman & Gilman's The Pharmacological Basis of Therapeutics, p. 1032; Katzung's Basic and Clinical Pharmacology, p. 1113.
Consequences of abrupt cessation
- Fatigue, weakness, malaise
- Nausea, vomiting, anorexia, weight loss
- Myalgia, arthralgia, fever
- Postural hypotension and hypoglycemia
- In severe cases: shock, circulatory collapse, and life-threatening adrenal crisis, especially during infection, trauma, surgery, or other physiologic stress.
Abrupt cessation can also cause:
- Recurrence or flare of the original disease for which steroids were prescribed.
- Glucocorticoid withdrawal syndrome, with fatigue, fever, muscle and joint pains, and mood symptoms, which can occur even without demonstrable cortisol deficiency.
Therefore
Glucocorticoids used for more than about 2-3 weeks, particularly at supraphysiologic doses, should generally be tapered gradually. Tapering allows ACTH secretion and adrenal cortisol synthesis to recover. Dose reduction is usually slower as the dose approaches normal physiologic replacement levels. Current Endocrine Society guidance likewise recommends individualized tapering because HPA-axis recovery varies substantially between people.
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