What is the approach to managing a patient with adrenal cortex disease?

Management Approach to Patients with Adrenal Cortex Disease

The management of adrenal cortex disease requires prompt diagnosis, appropriate hormone replacement therapy, and comprehensive patient education to prevent potentially fatal adrenal crises. 1

Diagnostic Approach

Initial Evaluation

• Assess for characteristic symptoms:
  • Nonspecific symptoms: fatigue, weakness, malaise, anorexia, weight loss, nausea, diarrhea, joint/back pain
  • In primary adrenal insufficiency: hyperpigmentation
  • Emergency presentations: orthostatic hypotension, fever, hypoglycemia, severe abdominal pain, dehydration, altered mental status 1, 2

Laboratory Testing

• First-line tests:

  • Morning cortisol and ACTH levels (primary vs. secondary differentiation)
  • Electrolytes (hyponatremia, hyperkalemia in primary insufficiency)
  • Blood glucose (hypoglycemia)

• Confirmatory testing:

  • ACTH stimulation test (Synacthen test)
  • Metyrapone test: administer 30 mg/kg (max 3g) at midnight with food, measure 11-desoxycortisol and ACTH the following morning 3
  • An intact HPA axis is indicated by 11-desoxycortisol >70 mcg/L 3

Imaging

• CT or MRI of abdomen for adrenal gland visualization
• Chest CT for metastatic disease if adrenal cancer suspected
• Consider FDG-PET in selected cases 4

Treatment Approach

Hormone Replacement Therapy

For Adrenal Insufficiency

1. Glucocorticoid replacement:

   • Hydrocortisone 10-30mg daily in divided doses (typically 15-20mg in morning, 5-10mg in afternoon) 1
   • Mimic physiological cortisol secretion pattern

2. Mineralocorticoid replacement:

   • Fludrocortisone 0.1mg daily (for primary adrenal insufficiency)
   • Adjust based on plasma renin activity and clinical assessment 1

For Adrenocortical Carcinoma (ACC)

1. Surgical management:

   • Complete surgical extirpation (R0 resection) is the mainstay of potentially curative approaches
   • Include locoregional lymphadenectomy 4

2. Adjuvant therapy:

   • Mitotane for patients with incomplete resection (R1, Rx stage III) or high-risk features (Ki67>10%)
   • Consider adjuvant radiotherapy to tumor bed for R1 and Rx resections 4

3. Advanced/metastatic disease:

   • Fit patients with high tumor volume and rapid progression: combination cytotoxic chemotherapy plus mitotane (EDP-M)
   • Less fit patients or those with low tumor burden and slow progression: mitotane monotherapy with or without locoregional options 4

Special Situations

Stress Dosing for Adrenal Insufficiency

• Minor illness (fever, cold): Double oral glucocorticoid dose
• Severe illness/vomiting/diarrhea: 100mg hydrocortisone IM/IV
• Major surgery: 100mg hydrocortisone IM before anesthesia, then 100mg IM every 6 hours until oral intake possible 1
• Minor surgery/dental procedures: 100mg hydrocortisone IM before procedure, double oral dose for 24 hours 1

Adrenal Crisis Management

• Immediate treatment with 100mg hydrocortisone IV bolus
• Follow with 100-300mg/day as continuous infusion or divided doses
• Rapid IV isotonic saline administration
• Hourly blood glucose monitoring if fasting >4 hours 1, 5

Pregnancy Considerations

• Hydrocortisone dose may need 2.5-10mg daily increase in third trimester
• Fludrocortisone dose may need increase during late pregnancy
• During delivery: 100mg hydrocortisone bolus, repeated every 6 hours if necessary 1

Patient Education and Follow-up

Essential Education Points

• Stress dosing instructions
• Emergency injectable hydrocortisone use
• Medical alert bracelet/card
• Recognition of early warning signs of adrenal crisis 1

Follow-up Schedule

• For resected ACC: Regular follow-up every 3 months including abdominal CT/MRI, thoracic CT, and monitoring of initially elevated steroids
• After 2 years, intervals may gradually increase
• Continue follow-up for at least 10 years 4
• For adrenal insufficiency: Regular monitoring to assess replacement adequacy and watch for signs of over/under-replacement 1

Common Pitfalls and Caveats

• Delayed diagnosis due to nonspecific symptoms
• Inadequate stress dosing during illness or procedures
• Failure to recognize adrenal crisis
• Insufficient patient education about emergency management
• Inappropriate glucocorticoid dosing leading to under or over-replacement 1, 2
• Higher doses of hydrocortisone may negatively impact bone mineral density 1
• Avoid metyrapone testing in patients with suspected adrenal insufficiency without first confirming adrenal response to exogenous ACTH 3