What is the recommended steroid replacement therapy regimen after resection of an Adrenocorticotropic hormone (ACTH) secreting tumor?

Steroid Replacement Therapy After ACTH-Secreting Tumor Resection

After resection of an ACTH-secreting tumor, patients should receive hydrocortisone 100 mg intravenously at induction, followed by a continuous infusion of 200 mg/24 hours while nil by mouth, then transition to double the normal oral hydrocortisone dose for 48 hours or up to a week following major surgery. 1

Pathophysiology and Rationale

The removal of an ACTH-secreting tumor results in sudden withdrawal of excessive ACTH stimulation to the adrenal glands, which can lead to adrenal insufficiency. During the period of tumor presence:

• The hypothalamic-pituitary-adrenal (HPA) axis was suppressed due to excess ACTH and cortisol
• Normal corticotrophs in the pituitary were inhibited
• The contralateral adrenal gland may have atrophied

This creates a high risk for acute adrenal insufficiency post-operatively, which can be life-threatening if not properly managed.

Immediate Post-Operative Management

For the immediate post-operative period:

• Administer hydrocortisone 100 mg intravenously on induction 1
• Follow with continuous infusion of hydrocortisone 200 mg/24 hours 1
• Alternative: hydrocortisone 50 mg every 6 hours by intramuscular injection 1
• Continue this regimen while the patient is nil by mouth or experiencing post-operative vomiting 1

Transition to Oral Therapy

When the patient can take oral medications:

• Double the normal hydrocortisone replacement dose for 48 hours 1
• For major surgery, continue double dosing for up to a week 1
• Typical maintenance dose ranges from 15-25 mg/day in divided doses 2
• Common dosing schedule: 10 mg (morning) + 5 mg (noon) + 2.5 mg (afternoon) 2

Long-Term Management

After the initial post-operative period:

• Continue steroid replacement until recovery of the HPA axis 1
• Monitor morning cortisol levels to assess recovery
• A morning cortisol ≥8 μg/dl can indicate adequate adrenal function 3
• Recovery of the HPA axis may take months to years, and some patients may require lifelong replacement

Monitoring for Recovery

To assess recovery of the HPA axis:

• Check morning cortisol levels (8:00 AM) at regular intervals
• A cut-off value of 8 μg/dl can be used to evaluate HPA status 3
• Consider low-dose (1 μg) ACTH stimulation test at 6 weeks and repeat at 12 months 3
• Signs of over-replacement: weight gain, insomnia, peripheral edema 2
• Signs of under-replacement: lethargy, nausea, poor appetite, weight loss 2

Special Considerations

• All patients should receive medical alert identification indicating adrenal insufficiency 2
• Patient education on stress dosing is essential:
  • Minor illness with fever <38°C: double oral dose 2
  • Moderate illness with fever >38°C: triple oral dose 2
  • Severe illness or surgery: 100 mg hydrocortisone IV/IM before procedure, then every 6 hours 2

Common Pitfalls to Avoid

• Failure to provide adequate steroid coverage during the immediate post-operative period
• Tapering steroids too quickly before HPA axis recovery
• Not educating patients about stress dosing and emergency management
• Overlooking signs of adrenal insufficiency: hypotension, hyponatremia, hyperkalemia, hypoglycemia
• Not providing patients with emergency injectable hydrocortisone and instructions for use

Important Note

The need for steroid replacement is universal in patients with Cushing syndrome from ACTH-secreting tumors. In a study of 331 consecutive adrenalectomies, all patients with Cushing syndrome required steroid replacement therapy post-operatively 4. Failure to provide adequate steroid coverage can result in life-threatening adrenal crisis.