Adrenal Insufficiency (AI) from Exogenous Steroids (Prednisolone): Diagnosis, Risk, and Tapering Guide

🔬 Pathophysiology

Adrenal insufficiency (AI) occurs when the adrenal glands fail to produce sufficient cortisol. In the case of secondary AI, the cause is most often suppression of the hypothalamic-pituitary-adrenal (HPA) axis due to prolonged use of exogenous glucocorticoids, such as prednisolone.

Glucocorticoids exert negative feedback on the hypothalamus and pituitary:

• ↓ CRH from hypothalamus

• ↓ ACTH from anterior pituitary

• ⟶ Atrophy of adrenal cortex (especially zona fasciculata)

• ⟶ Impaired cortisol production

This suppression may persist weeks to months after discontinuation, especially if not tapered properly.

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🩺 Diagnosis and Clinical Features

📍 Signs and Symptoms of AI

Often nonspecific, symptoms may include:

• Fatigue, weakness

• Nausea, vomiting, abdominal pain

• Hypotension

• Hypoglycemia

• Hyponatremia (due to ↑ ADH)

• Weight loss

• Dizziness or syncope

• Psychiatric symptoms (e.g., depression, irritability)

May present as acute adrenal crisis if triggered by stress (e.g., infection, surgery).

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📌 General Thresholds for Risk of Adrenal Suppression (Prednisolone)

Prednisolone Dose	Duration	Risk of Adrenal Suppression
≥ 20 mg/day	≥ 3 weeks	High risk
5–20 mg/day	> 3 weeks	Intermediate risk
< 5 mg/day	Any duration	Low risk, unless prolonged over months
Any dose	< 3 weeks	Usually no risk (can stop abruptly)

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⚠️ Key Considerations

• Exogenous corticosteroids suppress the HPA axis, reducing endogenous cortisol.

• Abrupt cessation after prolonged use can trigger adrenal crisis, especially during stress.

• Even physiologic doses (e.g., 5–7.5 mg/day) can cause suppression if used chronically.

• Symptoms of AI often overlap with the underlying condition (e.g., rheumatoid arthritis), making diagnosis challenging.
  

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🔬 How to Assess for Adrenal Suppression

• Morning serum cortisol:

  • < 3 µg/dL: Strongly suggests adrenal suppression

  • 10–15 µg/dL: Usually rules out suppression

• Cosyntropin (ACTH) stimulation test:

  • Gold standard to confirm secondary adrenal insufficiency

  • Normal response = ↑ cortisol > 18–20 µg/dL after 30–60 minutes
    

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✅ Practical Approach to Tapering

• ≥ 20 mg/day for > 3 weeks:

  • Do not stop abruptly

  • Gradual taper over weeks to months

• Low-dose long-term steroids:

  • Consider HPA axis testing prior to discontinuation

• During illness, surgery, trauma:

  • May need stress-dose steroids even after tapering, if axis remains suppressed