What are the treatments for cortisol imbalance?

Treatment of Cortisol Imbalance

The treatment for cortisol imbalance depends on whether the patient has excess cortisol (Cushing syndrome) or cortisol deficiency (adrenal insufficiency), with surgical intervention being first-line for tumor-related causes and hormone replacement therapy for deficiency states. 1

Hypercortisolism (Cushing Syndrome)

Diagnosis

• Elevated 24-hour urine cortisol levels indicate Cushing syndrome 1
• Determine source by measuring ACTH levels:
  • Elevated ACTH suggests pituitary or ectopic source 1
  • Low/normal ACTH suggests adrenal source 1

Treatment Algorithm

1. ACTH-Dependent Cushing Syndrome (elevated ACTH)

   • Pituitary source (Cushing disease): Transsphenoidal surgery is first-line treatment 1
   • Ectopic source: Surgical removal of the tumor if possible 1
   • If tumor is unresectable:
     • Bilateral laparoscopic adrenalectomy OR
     • Medical management with adrenostatic agents 1

2. ACTH-Independent Cushing Syndrome (normal/low ACTH)

   • Benign adrenal tumor: Laparoscopic adrenalectomy 1
     • Postoperative corticosteroid supplementation required until HPA axis recovery 1
   • Malignant adrenal tumor: Open adrenalectomy with lymph node removal 1
     • Suspect malignancy if tumor >5cm or has irregular margins/local invasion 1
   • Bilateral multinodal hyperplasia:
     • Asymmetric cortisol production: Unilateral adrenalectomy of most active side 1
     • Symmetric cortisol production: Medical management 1

3. Medical Management Options

   • Ketoconazole (400-1200 mg/day) - most commonly used due to availability and tolerability 1
   • Mitotane - alternative adrenostatic agent 1
   • Octreotide - for ectopic ACTH if tumor is Octreoscan-positive 1

Management of Complications

• Monitor and treat cardiovascular complications (hypertension, heart failure) 1
• Address bone disease with calcium, vitamin D, and possibly bisphosphonates 1
• Evaluate for growth hormone deficiency, especially after surgical treatment 1

Hypocortisolism (Adrenal Insufficiency)

Diagnosis

• Morning cortisol <250 nmol/L with elevated ACTH during acute illness confirms primary adrenal insufficiency 1
• Low ACTH with low cortisol indicates secondary (central) adrenal insufficiency 1

Treatment Algorithm

1. Primary Adrenal Insufficiency

   • Maintenance therapy:
     • Hydrocortisone 15-25 mg daily in split doses (first dose upon waking, last dose ≥6 hours before bedtime) 1
     • Fludrocortisone 50-200 μg once daily for mineralocorticoid replacement 1
     • Advise liberal salt intake 1

2. Secondary Adrenal Insufficiency

   • Hydrocortisone replacement as above, but fludrocortisone typically not required 1
   • Evaluate and treat other pituitary hormone deficiencies 1

3. Adrenal Crisis Management

   • Immediate IV/IM hydrocortisone 100 mg followed by 100 mg every 6-8 hours until recovery 1
   • Rapid IV isotonic saline (0.9%) at 1 L/hour initially 1
   • Identify and treat precipitating cause (often infection) 1

Special Situations

• Surgery/Procedures: Increase hydrocortisone dose according to stress level 1

  • Major surgery: 100 mg IV before anesthesia, then 50 mg IV every 8 hours for 24 hours 1
  • Minor procedures: Double oral dose for 24 hours 1

• Stress Dosing: Patients should be educated to increase their dose during illness 1

Important Considerations

• All patients with adrenal insufficiency should wear medical alert identification and carry a steroid alert card 1
• Patients require education on stress dosing and emergency self-injection 1
• For patients on long-term corticosteroid therapy, consider alternate-day therapy to minimize HPA axis suppression 2
• Monitor patients annually for weight, blood pressure, electrolytes, and development of new autoimmune disorders 1
• Assess bone mineral density every 3-5 years to monitor for steroid-induced osteoporosis 1

Common Pitfalls

• Failure to recognize adrenal crisis as a medical emergency, which requires immediate treatment before completing diagnostic workup 1
• Inadequate stress dosing during illness or procedures, leading to adrenal crisis 1
• Not providing patients with emergency injection kits and proper education 1
• Overlooking the need for mineralocorticoid replacement in primary adrenal insufficiency 1
• Misinterpreting cortisol levels without considering diurnal variation or protein-binding effects 3, 4