Objective: To highlight and summarize current literature on Cushing disease (CD)-related morbidity and mortality, focusing on residual complications after "cure" and the changing role of pharmacologic therapy in CD.
Methods: Current journal articles on the consequences of untreated or undertreated CD, CD recurrence, and recent trends in CD treatment were collected from PubMed searches and analyzed in combination in view of the authors' clinical experience.
Results: Timely recognition and treatment of de novo and recurrent CD remains a singular clinical challenge. Chronic excess cortisol exposure leads to potentially irreversible sequelae and death, stressing the importance of early diagnosis and treatment. Disease relapse after primary pituitary adenomectomy is prevalent and recurrence may manifest decades after initial surgery. Increased risk for mortality and hypercortisolism-related complications in postsurgical CD patients may indicate persistent subclinical disease and further underscores the need for cautious, ongoing observation and testing. Potential long-term pharmacologic treatment options (e.g., pasireotide, mifepristone) have recently emerged that may provide biochemical and symptomatic remission for those with refractory CD, or those for whom surgery is contraindicated.
Conclusion: Delays in CD diagnosis, management, and follow-up are common and lead to increased adverse metabolic complications and mortality. Rapid recognition and treatment as well as vigilant monitoring are therefore essential. After surgical treatment, some patients may suffer from persistent subclinical CD that remains difficult to detect with routine testing. Although long-term pharmacologic treatment has historically been limited by adverse reactions or escape from response, new treatments may offer more options for patients with refractory disease.