Can a patient with primary adrenal insufficiency (PAI) experience fevers, chills, and sweats due to inadequate replacement steroid therapy while being treated with fluconazole for Coccidiomycosis?

Inadequate Steroid Replacement in Primary Adrenal Insufficiency Can Cause Fever, Chills, and Sweats During Coccidiomycosis Treatment

Yes, a patient with primary adrenal insufficiency who is not taking adequate replacement steroid therapy could experience fevers, chills, and sweats while being treated with fluconazole for coccidiomycosis. This presentation represents symptoms of an impending or early adrenal crisis that requires immediate intervention.

Mechanism and Presentation

The relationship between inadequate steroid replacement and these symptoms occurs through several mechanisms:

1. Adrenal Crisis Development:

   • Inadequate glucocorticoid replacement in PAI patients can lead to adrenal crisis, which commonly presents with fever, chills, and sweats 1, 2
   • Infections like coccidiomycosis create physiological stress that increases cortisol requirements, making previously adequate replacement doses insufficient 2

2. Fluconazole Interaction:

   • Fluconazole can potentially affect steroid metabolism and may require adjustment of steroid dosing 3
   • The FDA label for fluconazole specifically mentions adrenal insufficiency as a potential side effect 3
   • Azole antifungals, including fluconazole, can interfere with steroid metabolism 4

Management Algorithm

1. Immediate Intervention:

   • Administer stress-dose steroids immediately: 100mg hydrocortisone IV/IM bolus 2
   • Follow with continuous infusion of 200mg/24h or 50mg every 6 hours until stabilized 2
   • Provide fluid resuscitation with isotonic saline 2

2. Maintenance Therapy Adjustment:

   • During infection, increase maintenance glucocorticoid dose to at least 2-3 times the usual dose 2
   • For moderate illness with fever >38°C, triple the oral dose or use parenteral hydrocortisone 2
   • Monitor for signs of improvement: normalization of vital signs, resolution of symptoms

3. Fluconazole Considerations:

   • Continue fluconazole treatment for coccidiomycosis as prescribed
   • Be aware that fluconazole may require adjustment of steroid dosing 1, 3
   • Monitor for drug interactions between fluconazole and steroids 3

Important Clinical Considerations

• Warning Signs: Fever, chills, sweats, fatigue, nausea, vomiting, abdominal pain, and hypotension are early warning signs of adrenal crisis in PAI patients 1, 2

• Medication Interactions: The FDA label for fluconazole specifically mentions that "adrenal insufficiency has been reported in patients receiving azoles, including fluconazole" 3

• Monitoring Parameters:

  • Blood pressure (watch for orthostatic hypotension)
  • Serum electrolytes (particularly sodium and potassium)
  • Morning cortisol levels when stable
  • Clinical symptoms (fatigue, appetite, fever)

• Patient Education: All PAI patients should be educated about:

  • Stress dosing instructions
  • Recognition of early warning signs of adrenal crisis
  • Emergency injectable hydrocortisone use
  • Wearing a medical alert bracelet/card 2

Pitfalls and Caveats

• Don't Mistake for Worsening Infection: The symptoms of inadequate steroid replacement (fever, chills, sweats) can be misinterpreted as worsening coccidiomycosis, leading to inappropriate management.

• Avoid Delaying Steroid Increase: Any delay in increasing steroid doses during infection can precipitate full adrenal crisis, which has high mortality if untreated.

• Don't Overlook Drug Interactions: Fluconazole can interact with steroid metabolism, potentially requiring dose adjustments of replacement therapy 1, 3.

• Beware of Absorption Issues: Gastrointestinal symptoms from infection may impair oral steroid absorption, necessitating parenteral administration 5.

In conclusion, the symptoms described strongly suggest inadequate steroid replacement in the setting of infection and fluconazole treatment, requiring immediate intervention with stress-dose steroids to prevent progression to life-threatening adrenal crisis.