Does budesonide (corticosteroid) affect adrenal gland function?

Budesonide Can Cause Adrenal Gland Suppression

Yes, budesonide can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, potentially leading to adrenal insufficiency, though this risk is lower than with systemic corticosteroids. 1, 2

Mechanism and Evidence

Budesonide, like other corticosteroids, can affect the HPA axis through:

• Inhibition of ACTH secretion from the pituitary gland
• Direct suppression of adrenal cortisol production
• Negative feedback on the hypothalamus and pituitary 3

The FDA drug label for budesonide specifically warns about adrenal suppression as a potential adverse effect, noting that "when budesonide extended-release tablets are taken for a long period of time (chronic use), the adrenal glands do not make enough steroid hormones (adrenal suppression)" 2.

Risk Factors for Adrenal Suppression

The risk of adrenal suppression with budesonide depends on several factors:

• Dose: Higher doses increase risk 4
• Duration: Longer treatment periods increase risk 2
• Route of administration: Risk varies by delivery method
• Individual susceptibility: Some patients are more susceptible even at conventional doses 1
• Concomitant medications: Drug interactions can increase systemic exposure (e.g., itraconazole) 5

Route-Specific Considerations

Inhaled Budesonide

• Low-to-medium doses generally have minimal effects on the HPA axis in most patients 1
• However, case reports document adrenal suppression even at standard doses:
  • A 7-year-old girl developed growth retardation, centripetal weight gain, and Cushingoid features with unmeasurable cortisol levels after treatment with 600-1000 μg daily 6
  • An 8-year-old boy developed malaise and lowered serum cortisol levels with just 400 μg daily 6

Oral Budesonide

• Higher risk of systemic effects than inhaled formulations
• Can cause complete suppression of the HPA axis 7
• Abrupt discontinuation can precipitate an Addisonian crisis 7

Clinical Implications

1. Monitoring recommendations:

   • For children on long-term therapy: Monitor growth, morning cortisol levels, and consider periodic ACTH stimulation testing 1
   • For adults: Be alert for signs of adrenal insufficiency (fatigue, weakness, nausea, vomiting, low blood pressure) 2

2. Drug interactions:

   • CYP3A4 inhibitors (like itraconazole) can dramatically increase systemic budesonide exposure and risk of adrenal suppression 5
   • Avoid grapefruit juice which can increase budesonide blood levels 2

3. Discontinuation:

   • Taper budesonide slowly rather than stopping abruptly to allow recovery of the HPA axis 2
   • Recovery of adrenal function may take months after discontinuation 5

Special Populations

Children

• More vulnerable to adrenal suppression effects
• May experience growth suppression and delayed development 1
• The Canadian Association of Gastroenterology specifically recommends against budesonide for maintenance therapy in pediatric Crohn's disease due to adrenal suppression risk 1

Elderly

• May have increased susceptibility to adrenal suppression
• British Thoracic Society guidelines note clinically important adrenal suppression with inhaled corticosteroids in bronchiectasis patients 1

Conclusion

While budesonide generally has fewer systemic effects than traditional corticosteroids, it can still cause clinically significant adrenal suppression. Healthcare providers should be aware of this risk, monitor patients appropriately, and take precautions when discontinuing therapy.