Adrenal Insufficiency in Aspergillosis: Important Risks for Patients and GPs

🫁 Who is at Risk?
People with aspergillosis — especially ABPA (Allergic Bronchopulmonary Aspergillosis) and CPA (Chronic Pulmonary Aspergillosis) — are often treated with:

• Steroids (inhaled or oral, such as fluticasone or prednisolone)
• Azole antifungal medications (like itraconazole, voriconazole, posaconazole)

Both of these can affect the adrenal glands, though azole antifungals only do so indirectly in combination with a steroid medication. When used together, or when steroids are used on their own for long periods of time at a high dose, they can significantly increase the risk of a serious condition called adrenal insufficiency (AI) — when the body can’t produce enough cortisol to respond to stress or illness.

💊 Why Azole Antifungals Make This Worse
Azoles (itraconazole, voriconazole, posaconazole) block liver enzymes (CYP3A4) that normally break down inhaled or oral steroids. As a result:

• Even inhaled steroids (like fluticasone or budesonide) can build up in the body

This can lead to systemic steroid effects, including:

• Adrenal suppression
• Cushing’s-like symptoms (weight gain, moon face, skin thinning)
• Higher risk of adrenal crisis if steroids are stopped too fast or during illness

This is especially well documented with fluticasone + itraconazole — a known high-risk combination.

🚨 What is Adrenal Insufficiency?
Adrenal insufficiency means your adrenal glands cannot produce enough cortisol, the hormone your body needs to:

• Regulate blood pressure and sugar
• Respond to infections and illness
• Maintain energy, mood, and salt balance

Without cortisol, even a minor illness can become life-threatening — this is called an adrenal crisis.

🔍 Warning Signs of Adrenal Suppression

• Fatigue and muscle weakness
• Low mood or confusion
• Weight loss or loss of appetite
• Dizziness when standing (low blood pressure)
• Nausea, abdominal pain
• Skin changes (e.g. thin skin, stretch marks, bruising)
• Cushingoid appearance (round face, fat on upper back)
• During stress (infection, surgery, trauma), people may:
• Vomit or collapse
• Become drowsy or disoriented
• Experience dangerously low blood pressure or blood sugar

🛡️ What GPs and Patients Should Do
For GPs:

• Be alert to the interaction between inhaled corticosteroids and azoles
• If a patient is using inhaled fluticasone or budesonide and starts azoles:
• Consider switching to a non-CYP3A4-metabolised inhaler (e.g. beclometasone)
• Monitor for signs of adrenal suppression or Cushing’s
• If adrenal insufficiency is suspected:
• Arrange morning cortisol testing
• Consider Short Synacthen Test (SST)
• Educate patients on sick day rules and ensure:
• A steroid emergency card is provided
• An adrenal crisis plan is in place
• Emergency hydrocortisone is prescribed if needed

For Patients:

Tell your GP or specialist if you are on:

• • Azoles (like itraconazole, posaconazole)
  • Any form of steroids (inhaled, nasal, oral, injected)
• Never stop steroids suddenly — they may need to be reduced slowly
• Report symptoms like fatigue, nausea, or dizziness
• Ask about a sick day plan — you may need to double your steroid dose during illness
• If you become very unwell, tell emergency services you are at risk of adrenal crisis

💬 Summary
Adrenal insufficiency is a real and under-recognised risk in aspergillosis — especially when azole antifungals are used alongside inhaled or oral steroids. Patients and GPs should work together to prevent and manage this serious complication.