What is the primary treatment for Cushing's disease?

Treatment for Cushing Disease

Selective transsphenoidal adenomectomy performed by an experienced pituitary surgeon is the first-line treatment for Cushing's disease. 1, 2

Primary Treatment Approach

• Transsphenoidal surgery aims to remove the ACTH-secreting pituitary adenoma while preserving normal pituitary tissue 1
• Surgical success is significantly influenced by surgeon experience, with higher remission rates reported for specialists in pituitary surgery 1
• Early post-operative remission is associated with successful adenoma identification during surgery, younger patient age, smaller adenoma size, and absence of cavernous sinus or dural invasion 1
• Remission rates with transsphenoidal surgery range from 50-90%, making it the most effective initial intervention 3
• Pure endoscopic endonasal approaches have shown promising results with remission rates of approximately 80% and low rates of major complications 4

Management of Persistent or Recurrent Disease

When initial surgery fails to achieve remission, a stepwise approach is recommended:

1. Repeat Transsphenoidal Surgery

   • Consider for patients with visible tumor on MRI 1, 2
   • Can achieve biochemical remission in up to 93% of cases, particularly in pediatric patients 1, 2

2. Radiation Therapy

   • Indicated for recurrent disease not amenable to curative surgery 1, 2
   • Options include stereotactic radiotherapy, fractionated proton beam therapy, and gamma knife radiosurgery 1
   • Effects may take months to years to fully manifest 3

3. Medical Therapy

   • Used to reduce cortisol burden while awaiting definitive treatment effects 1, 2
   • Primary options include:
     • Metyrapone: Inhibits 11-beta-hydroxylation in adrenal cortex, reducing cortisol production 5
     • Ketoconazole: Adrenal steroidogenesis inhibitor 1, 2
   • Monitoring during treatment should include urinary free cortisol, salivary cortisol levels, and clinical symptoms 2
   • Consider changing treatment if cortisol levels remain elevated after 2-3 months on maximum tolerated doses 2

4. Bilateral Adrenalectomy

   • Reserved for severe refractory cases or life-threatening emergencies 2
   • Provides definitive control of hypercortisolemia but requires lifelong glucocorticoid replacement 3

Important Clinical Considerations

• Cushing's disease is associated with significant morbidity including metabolic disorders, hypertension, immunosuppression, and neurocognitive changes 6, 7
• Early diagnosis and prompt treatment are crucial to limit long-term complications 7
• Bilateral inferior petrosal sinus sampling (BIPSS) may help lateralize ACTH secretion when MRI shows no visible lesion, with 75-80% predictive value for lateralization 1
• Lifelong follow-up is essential as recurrence can occur up to 15 years after apparent surgical cure 1, 2
• Monitor for development of hypopituitarism following surgery or radiotherapy 1
• Evaluate for growth hormone deficiency 3-6 months postoperatively in patients who have not completed linear growth 1, 2

Medication Side Effects to Monitor

• Metyrapone may cause hirsutism, dizziness, joint pain, fatigue, hypokalemia, nausea, and potential hyperandrogenism with advanced bone age in children 2
• Ketoconazole can cause hepatotoxicity, gastrointestinal disorders, and adrenal insufficiency 2
• Regular monitoring of medication efficacy and side effects is essential for optimal management 2