Management of Cushing's Disease

First-Line Treatment: Surgical Approach

The Endocrine Society recommends selective transsphenoidal adenomectomy as 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
Surgery should be performed by an experienced surgeon specializing in pituitary surgery, as surgeon experience is a significant predictor of success 1, 3
Early post-operative remission is associated with successful identification of the adenoma during surgery, while 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

Repeat transsphenoidal surgery is considered for patients with persistent or recurrent disease, especially when tumor is visible on MRI, with early biochemical remission rates of up to 93% reported in pediatric patients 1, 4
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, 5
Medical therapy, including metyrapone or ketoconazole as adrenal steroidogenesis inhibitors, is used to reduce cortisol burden while awaiting definitive surgery or the effect of radiotherapy 2, 4, 6

Lifelong follow-up is essential as recurrence can occur up to 15 years after apparent surgical cure, with monitoring for development of hypopituitarism following surgery or radiotherapy 1, 6
Evaluate for growth hormone deficiency 3-6 months postoperatively in patients who have not completed linear growth 7

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% 3

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, as recommended by the Endocrine Society 8
Pituitary hormone deficiencies are common after surgical or radiotherapeutic cure of Cushing's disease, with growth hormone deficiency being the most frequent pituitary deficit, according to the Endocrine Society 8

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, as suggested by the Endocrine Society 8