Disease symptoms, surgery outcomes vary with patient age
Older patients show fewer classic symptoms, face higher risk from surgery
Older Cushing’s disease patients less frequently present classical symptoms of the disease, and have more coexistent conditions and larger tumors than those who develop the disease at a younger age.
That’s according to a study that analyzed patients at several sites in the U.S. who underwent surgery to remove pituitary gland tumors, which cause the disease.
Researchers also found that older patients tend to have a higher risk of developing postoperative complications, including thromboembolism, or the formation of blood clots inside deep veins that may obstruct blood flow.
“These findings underscore the need for tailored diagnostic and therapeutic approaches across age groups, with a focus on managing long-term comorbidities and optimizing surgical outcomes,” the researchers wrote.
The study, “Cushing’s Disease Clinical Phenotype and Tumor Behavior Vary with Age: Diagnostic and Perioperative Implications,” was published in The Journal of Clinical Endocrinology and Metabolism.
Cushing’s treatment
Cushing’s syndrome encompasses conditions driven by chronically high levels of the hormone cortisol. Cushing’s disease, one of its most common forms, is caused by pituitary tumors that produce and release large amounts of adrenocorticotropic hormone (ACTH). ACTH triggers the adrenal glands, sitting atop the kidneys, to produce excessive amounts of cortisol that ultimately drive Cushing’s symptoms.
The first line of treatment for Cushing’s disease is transsphenoidal surgery, a minimally invasive surgical procedure used to remove the disease-causing pituitary tumor through the nose. Radiation therapy may also be used to destroy cancer cells in patients who are not eligible for surgery or in whom the procedure failed to completely remove the tumor. Medications that reduce cortisol levels may also be used in combination with surgery or radiation therapy, or as a first-line treatment in cases where neither surgery nor radiation are considered good or viable options.
However, “little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing’s disease (CD) with aging,” the researchers wrote.
The team, led by researchers at the University of California Los Angeles, reviewed data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) for patients with Cushing’s disease who underwent transsphenoidal surgery at 11 centers in the U.S. between 2003 and 2023. They evaluated 608 patients with a median age of 44 at the time of surgery. Some 81.6% were women.
The researchers found that as patients’ ages increased, so did the number of coexistent conditions, tumor size, and Knosp grade — a classification system that assesses the extent of pituitary tumor invasion into surrounding structures and the likelihood of disease remission after tumor removal, with higher values indicating greater invasion and a lower chance of remission.
Rates of postoperative thromboembolic disease also increased as patients became older.
Younger patients most commonly had hallmark features of Cushing’s, including weight gain, facial rounding and redness, acne, abdominal stretch marks, excessive growth of body hair, fat buildup between the shoulder blades, and menstrual irregularities.
Older patients less frequently had common Cushing’s symptoms. They also had lower 24-hour urinary free cortisol levels before surgery and lower Ki-67 indices. Ki-67 is a cell proliferation marker; high Ki-67 indices indicate rapid cell division, suggesting that a tumor is more likely to grow and spread.
Obstructive sleep apnea, a condition characterized by blockage or narrowing of the airways during sleep that interrupts breathing, and infections were also more common in older patients.
The researchers said these “age-related differences suggest a more indolent tumor behavior in older patients, potentially contributing to delayed diagnosis and increased perioperative risk.”
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