Julie M. Silverstein, MD, Professor of Medicine and Neurological Surgery, and Medical Director of the Pituitary Center in the Division of Endocrinology, Metabolism & Lipid Research at WashU Medicine, is co-author of a study published in The Journal of Clinical Endocrinology & Metabolism. The article, titled “Cushing Disease Clinical Phenotype and Tumor Behavior Vary With Age: Diagnostic and Perioperative Implications,” examines how age influences the clinical features, tumor biology, and surgical outcomes of Cushing disease.
Cushing disease is a rare endocrine disorder caused by a pituitary tumor that leads to excess cortisol production. Using data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID), the research team evaluated 608 patients treated with transsphenoidal tumor resection at 11 medical centers between 2003 and 2023.
The investigators found that Cushing disease presents and behaves differently depending on a patient’s age. Younger patients were more likely to show classic symptoms such as weight gain, facial rounding, unwanted hair growth, skin changes, and menstrual irregularities. Older patients often had fewer hallmark features but more severe health issues. “Increasing age was associated with increasing comorbidities, frailty, rates of postoperative thromboembolic disease, Knosp grade, tumor size, and postoperative cortisol and adrenocorticotropin nadirs,” the study reports.
Furthermore, the study notes that “age plays a critical role in how Cushing disease manifests and responds to treatment” and that “recognizing these differences can help clinicians improve diagnosis, tailor surgical planning, and manage postoperative risks more effectively.” Older adults often experience a less classic, more indolent form of the disorder, which can delay diagnosis and increase perioperative risk. The authors emphasize the importance of developing age-specific diagnostic and therapeutic strategies to improve outcomes and long-term care.
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 9, September 2025, Pages 2595–2604, https://doi.org/10.1210/clinem/dgae904