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

Treatment for Pituitary Microadenoma Causing Cushing's Disease

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

Primary Treatment: Surgical Approach

Transsphenoidal Surgery

• Selective adenomectomy is strongly recommended as first-line therapy (strong recommendation, moderate-quality evidence) 1
• Surgery should be performed by an experienced pituitary surgeon to maximize success rates
• Benefits of selective adenomectomy:
  • Maximizes preservation of normal pituitary tissue 1
  • Low rates of post-operative hypopituitarism in large studies 1
  • Remission rates of 75-80% in adults 2

Predictors of Surgical Success

• Identification of adenoma during surgery
• Younger age
• Smaller adenoma size
• Absence of cavernous sinus or dural invasion
• Post-operative morning serum cortisol level <1 μg/dl (<28 nmol/l) 1

Surgical Considerations

• Surgeon experience is a critical predictor of success 1
• Selective microadenomectomy can be technically challenging, especially in children 1
• Bilateral inferior petrosal sinus sampling (BSIPSS) may help lateralize the tumor when not visible on MRI, with predictive value for lateralization of 75-80% 1

Management of Persistent or Recurrent Disease

Repeat Surgery

• Consider repeat transsphenoidal surgery for persistent or recurrent disease (moderate recommendation, low-quality evidence) 1
• Early biochemical remission rates of up to 93% have been reported with repeat surgery 1

Radiotherapy

• Offer radiotherapy to patients with recurrent disease not amenable to curative surgery (strong recommendation, moderate-quality evidence) 1
• Options include:
  • Focal external beam radiotherapy
  • Stereotactic radiotherapy
  • Fractionated proton beam radiotherapy
  • Gamma knife radiosurgery
• Radiotherapy is typically initiated 2-4 weeks after unsuccessful surgery 1
• For fractionated treatment, a total dose of 45 Gy in 25 fractions over 35 days is effective 1

Medical Therapy

• Medical therapies are primarily used:
  1. As bridging therapy before surgery
  2. When awaiting effects of radiotherapy
  3. When surgery is contraindicated
• Options include:
  • Ketoconazole (64% UFC normalization) 2
  • Metyrapone (rapid cortisol reduction) 2
  • Osilodrostat (86% UFC normalization) 2
  • Pasireotide (15-26% UFC normalization) - FDA approved for adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative 2, 3
  • Cabergoline (~40% efficacy) 2
  • Mifepristone (improves hyperglycemia and weight gain) 2

Bilateral Adrenalectomy

• Consider as last resort when other treatments fail 2
• Induces adrenal insufficiency requiring lifelong replacement therapy

Follow-up and Monitoring

• Lifelong follow-up is essential due to potential recurrence up to 15 years after apparent surgical cure 1
• Monitor:
  • 24-hour urinary free cortisol
  • Morning serum cortisol
  • Late-night salivary cortisol 2
  • Clinical symptoms of recurrence

Important Considerations and Pitfalls

• Surgical expertise matters: Success rates vary significantly based on surgeon experience 1
• Recurrence risk: Despite initial remission, recurrence can occur years after successful treatment 1
• Medical therapy monitoring: Each medication requires specific monitoring (e.g., liver function for ketoconazole, glycemic control for pasireotide) 2
• Cyclical Cushing's syndrome: Can complicate diagnosis and treatment monitoring 2
• Adrenal insufficiency risk: Post-surgical cortisol levels must be monitored to detect and manage adrenal insufficiency

Treatment Algorithm

1. First-line: Transsphenoidal selective adenomectomy
2. If persistent/recurrent disease:
   • Consider repeat transsphenoidal surgery
   • If not amenable to surgery → radiotherapy
3. While awaiting definitive treatment effects:
   • Medical therapy to control hypercortisolism
4. If all other treatments fail:
   • Consider bilateral adrenalectomy