Is Korlym (mifepristone) an option for a patient with adrenal insufficiency and diabetes?

Korlym (Mifepristone) is Not Recommended for Patients with Adrenal Insufficiency and Diabetes

Korlym (mifepristone) is contraindicated in patients with adrenal insufficiency as it may worsen their condition by blocking the action of cortisol at the receptor level, potentially precipitating an adrenal crisis. 1

Rationale for Contraindication

Mifepristone is a glucocorticoid receptor antagonist that works by blocking the effects of cortisol. While this mechanism is beneficial in treating Cushing's syndrome (hypercortisolism), it poses significant risks in patients with adrenal insufficiency:

1. Mechanism of Action: Mifepristone blocks glucocorticoid receptors, preventing cortisol from exerting its effects 2

2. Risk of Adrenal Crisis: In adrenal insufficiency, patients already have insufficient cortisol production and require replacement therapy. Blocking the limited available cortisol could precipitate a life-threatening adrenal crisis 1, 3

3. Impact on Diabetes Management: While mifepristone can improve glycemic control in Cushing's syndrome patients, in adrenal insufficient patients with diabetes, it could destabilize glucose control by interfering with the necessary glucocorticoid replacement therapy 2

Appropriate Management for Adrenal Insufficiency

Instead of Korlym, patients with adrenal insufficiency should receive:

1. Glucocorticoid Replacement

• Hydrocortisone is the preferred glucocorticoid replacement (15-25 mg daily in divided doses) 1, 4
• Typical dosing schedule: 2/3 of the dose in the morning and 1/3 in the afternoon to mimic physiological cortisol rhythm 1
• Alternative regimens may include prednisolone or dexamethasone in specific circumstances 3

2. Mineralocorticoid Replacement (for Primary Adrenal Insufficiency)

• Fludrocortisone 0.05-0.2 mg daily 3, 1
• Dose adjusted based on blood pressure, electrolytes, and presence of edema 3

3. Special Considerations for Diabetes

• Glucocorticoid replacement must be carefully balanced to avoid both under- and over-replacement, which can affect glycemic control 5
• Blood glucose monitoring should be more frequent during dose adjustments 1
• Diabetes medications may need adjustment based on glucocorticoid dosing 1

Management During Stress or Surgery

Patients with adrenal insufficiency require increased glucocorticoid doses during periods of stress, illness, or surgery:

• Major surgery: Hydrocortisone 100 mg IV at induction, followed by continuous infusion of 200 mg/24h until oral intake is possible 3
• Minor procedures: Hydrocortisone 2 mg/kg IV or IM at induction 3
• Post-operative care: Double usual oral doses for 24-48 hours after minor procedures, tapering to normal doses over several days 3

Potential Pitfalls in Management

1. Failure to recognize adrenal crisis: Symptoms include hypotension, nausea, vomiting, abdominal pain, confusion, and hypoglycemia 1

2. Inadequate stress dosing: Insufficient glucocorticoid coverage during illness or procedures can precipitate adrenal crisis 1, 5

3. Drug interactions: Several medications can affect glucocorticoid metabolism, requiring dose adjustments 3:

   • Medications requiring increased hydrocortisone: Anti-epileptics, barbiturates, antituberculosis drugs
   • Medications requiring decreased hydrocortisone: Grapefruit juice, licorice

4. Perioperative management: All patients on glucocorticoid therapy for longer than 1 month who undergo surgery need adequate perioperative glucocorticoid replacement 3

Conclusion

For a patient with adrenal insufficiency and diabetes, appropriate management includes proper glucocorticoid and mineralocorticoid replacement therapy, careful monitoring of both conditions, and education about stress dosing. Korlym (mifepristone) is not an appropriate treatment option as it would antagonize the already deficient cortisol action, potentially leading to life-threatening complications.