What is the primary treatment for Cushing's disease?

Primary Treatment for Cushing's Disease

Selective transsphenoidal adenomectomy is the first-line treatment for Cushing's disease, performed by an experienced pituitary surgeon with the goal of removing the ACTH-secreting adenoma while preserving normal pituitary tissue. 1, 2

Surgical Approach

• Transsphenoidal surgery is considered the treatment of choice once the diagnosis of Cushing's disease has been established 1, 3
• The procedure should be performed by an experienced surgeon specializing in pituitary surgery, as surgeon experience is a significant predictor of success 1
• Early post-operative remission is associated with successful identification of the adenoma during surgery 1
• Long-term remission correlates with younger age, smaller adenoma size, absence of cavernous sinus or dural invasion, and morning serum cortisol <1 μg/dl after surgery 1

Surgical Outcomes and Monitoring

• Remission rates of approximately 75% can be expected 5 years after surgery 3
• Serum cortisol measurements at 6-12 weeks after transsphenoidal surgery provide better discrimination of continuing remission than levels obtained within 2 weeks of surgery 4
• Cortisol levels less than 35 nmol/L at 6-12 weeks post-surgery suggest a favorable long-term outcome 4
• To assess possible recurrence, patients in remission should receive 6-monthly clinical examination, 24-hour urinary free cortisol measurements, electrolytes, and morning serum cortisol for at least 2 years, followed by lifelong annual clinical assessment 5

Management of Persistent or Recurrent Disease

• Repeat transsphenoidal surgery may be considered for patients with persistent or recurrent disease, especially when tumor is visible on MRI 1, 2
• Radiotherapy is indicated for recurrent disease not amenable to curative surgery, with options including stereotactic radiotherapy, fractionated proton beam therapy, and gamma knife radiosurgery 1, 2
• Medical therapy with adrenal steroidogenesis inhibitors (metyrapone or ketoconazole) can be used to reduce cortisol burden while awaiting definitive surgery or the effect of radiotherapy 1, 2
• For patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative, pasireotide (SIGNIFOR LAR) is indicated at an initial dose of 10 mg administered by intramuscular injection once every 4 weeks 6

Important Clinical Considerations

• Bilateral inferior petrosal sinus sampling (BIPSS) may help lateralize pituitary ACTH secretion when no lesion is visible on MRI, with predictive value for lateralization of 75-80% 1
• Even with sophisticated imaging, tiny microadenomas may not be directly visualized, making the surgical procedure technically challenging 3
• Recurrences may occur even in patients who initially achieve remission, highlighting the importance of long-term follow-up 3, 7
• Pituitary hormone deficiencies are common after surgical or radiotherapeutic cure of Cushing's disease, with growth hormone deficiency being the most frequent pituitary deficit 5

Long-term Follow-up Considerations

• Lifelong follow-up is essential as recurrence can occur up to 15 years after apparent surgical cure 1, 2
• Monitoring for development of hypopituitarism following surgery or radiotherapy is necessary 1
• Evaluation for growth hormone deficiency should be performed 3-6 months postoperatively in patients who have not completed linear growth 1, 2
• Long-term monitoring for psychiatric and neurocognitive co-morbidities following remission of Cushing's disease should be considered, as cognitive and memory problems may persist in approximately 25% of patients despite cure 5