Chapter 15 - Cushing's disease

Abstract

Cushing's disease (CD) is caused by a pituitary tumor secreting corticotropin (ACTH), leading to cortisol excess. Patients with CD comprise approximately 70% of patients with endogenous Cushing's syndrome (CS). If the diagnosis and treatment are delayed, patients with CD may suffer the deleterious consequences of hypercortisolism, leading to significant morbidity and mortality. The diagnosis of CD is complex and includes two separate steps: establishing the presence of pathologic hypercortisolism and identifying the underlying cause. The management of CD usually includes transsphenoidal pituitary surgery (TSS) as the primary form of therapy. Pituitary surgery by the most experienced surgeons leads to remission of CD in 70-90% of patients. Recurrence of CD may occur in up to 25% of patients on long-term follow-up. Patients with recurrent CD may be treated with repeat TSS, radiation therapy to the pituitary with interim medical therapy (including steroidogenesis inhibitors, centrally acting agents or a glucocorticoid receptor antagonist) or bilateral adrenalectomy. Improvements in diagnosis and management of CD have led to higher patient survival. However, quality of life is impaired on long-term follow-up in some patients, even those in remission. Better understanding of the pathogenesis of CD may lead to the development of more effective therapies.