What is the main treatment for a pituitary adenoma causing Cushing's disease?

Treatment for Pituitary Adenoma Causing Cushing's Disease

Selective transsphenoidal adenomectomy is the first-line treatment of choice for patients with Cushing's disease caused by a pituitary adenoma. 1

Primary Treatment Approach

Transsphenoidal surgery offers several key advantages:

• Maximizes preservation of normal pituitary tissue
• Low rates of post-operative hypopituitarism
• High remission rates (approximately 80% of patients) 1, 2
• Can be effective even with normal MRI findings 3

The endoscopic approach is preferred over microscopic transsphenoidal surgery, particularly in children and adolescents, as it potentially better preserves pituitary function 4.

Surgical Considerations

• Surgery should be performed by experienced pituitary surgeons (performing at least 50 pituitary operations per year) 4
• Morning serum cortisol level <1 μg/dl post-operatively is a strong predictor of surgical success 1
• Complete resection typically results in ACTH deficiency due to suppression of normal corticotrophs by pre-existing hypercortisolemia 5
• Strict fluid and electrolyte balance monitoring is essential peri-operatively and post-operatively 4

Management of Persistent or Recurrent Disease

If initial surgery fails to achieve remission, several second-line options are available:

1. Repeat transsphenoidal surgery

   • Consider when residual tumor is visible on MRI
   • Can achieve early biochemical remission rates up to 93% 1
   • Carries increased risk of hypopituitarism 6

2. Radiation therapy

   • Options include focal external beam radiotherapy, stereotactic radiotherapy, fractionated proton beam radiotherapy, and gamma knife radiosurgery
   • Typically initiated 2-4 weeks after unsuccessful surgery
   • Fractionated radiotherapy (45 Gy in 25 fractions over 35 days) achieves biochemical remission in approximately 80% of patients 1
   • Requires distance of 3-5 mm between tumor and optic chiasm to limit damage 1

3. Medical therapy

   • Used to control hypercortisolism while awaiting definitive treatment or when surgery/radiation is contraindicated
   • First-line medications include:
     • Ketoconazole (400-600 mg/day initially, increased to 800-1,200 mg/day until cortisol normalization)
     • Metyrapone (provides rapid cortisol reduction)
     • Osilodrostat (86% UFC normalization rate) 1

4. Bilateral adrenalectomy

   • May be appropriate when other options have failed
   • Particularly suitable for women desiring fertility without visible residual tumors 2

Post-Treatment Monitoring

• Clinical examination and laboratory tests (24h UFC, electrolytes, morning serum cortisol) every 6 months for at least 2 years
• Annual clinical assessment thereafter for patients in remission
• Monitoring for pituitary hormone deficiencies and psychiatric/neurocognitive co-morbidities 1

Special Considerations

• Complications of transsphenoidal surgery include changes in water metabolism and AVP regulation (diabetes insipidus in 26%, SIADH in 14%) 4
• Hypopituitarism occurs in 25-50% of patients receiving radiation therapy and increases over time 1
• In children, transsphenoidal surgery is effective even with incompletely pneumatized sphenoid sinuses 4

Surgical remission rates are notably different based on tumor visibility: 84% for microadenomas, 92% for macroadenomas, but significantly lower for patients with no visible adenoma on MRI 7.