Cushing’s Treatment Needs Better Therapies to Improve Surgical Outcomes, Study Shows

A retrospective analysis shows that nearly 30 percent of patients with Cushing’s disease (CD) are not able to control the levels of cortisol in their blood, despite multiple treatments. 

The study, “Biochemical Control During Long-term Follow-up of 230 Adult Patients with Cushing’s Disease: a Multi-center Retrospective Study,” which was published in the journal Endocrine Practice, reveals the need for new, more efficient therapies for this patient population.

The research was led by Beverly M.K. Biller, MD, an endocrinologist at Massachusetts General Hospital in Boston, and a professor of medicine at Harvard Medical School. The scientists focused on the effectiveness of treatment outcomes for CD patients.

CD is characterized by excessive blood levels of the hormone cortisol caused by a pituitary tumor. The disease can occur at all ages in men and women, although data from the U.S. shows that female adults 20 to 50 years old are more susceptible.

Inadequately-treated CD results in significant mortality and multiple morbidities, such as hypertension, glucose intolerance and diabetes, obesity, thrombosis, or depression.

The primary treatment for CD is surgery to remove the tumor in the pituitary. A subsequent operation, bilateral adrenalectomy (removal of adrenal glands), radiotherapy, and medical treatment are used for recurrent disease. Nevertheless, information about the success of these therapies, or a combination of them, in the remission of chronic CD is lacking and could be important in improving long-term outcomes.

The study included 230 CD patients from eight pituitary centers in four major U.S. regions: The Northeast, Midwest, South, and West. Subjects had been diagnosed within the past 20 years after the age of 18.

The results showed 79 percent of the patients were female (median age at diagnosis 39 years) and that the mean length of follow-up was three years. The most common co-morbidities were hypertension (67.3%), polycystic ovary syndrome, an endocrine system disorder characterized by enlarged ovaries containing small collections of fluid, called follicular cysts (43.5%), and high cholesterol (41.5%).

The most prevalent symptoms before initial CD treatment included weight gain, easy bruising, fatigue, muscle weakness, hirsutism (abnormal hair growth in women), headache, and anxiety.

Biochemical control of CD with initial pituitary surgery was successful in 41.4% of patients, not successful in 50%, and undetermined in 8.6%. At the end of follow-up, pharmacotherapy, radiotherapy, and/or bilateral adrenalectomy, had enabled control of cortisol levels in 49.1% of patients. But there were still 29.9% of patients who did not see their disease controlled after treatment, and 21% had undetermined outcomes.

The lack of disease control in approximately 30 percent of patients at the end of follow-up shows that, despite multiple treatments, long-term control is not achieved in a substantial number of patients with CD, demonstrating that more effective multi-modal therapies are necessary.

The observed remission after primary surgery of approximately 41 percent was lower than that found in earlier studies. This could be due to the inclusion of a larger proportion of macroadenomas (a pituitary tumor larger than 10 mm) in the present study, the authors say. The data also “illustrate that there are different surgical outcomes across a range of medical centers, surgeons, and geographic regions,” and highlight “a need for improvement in surgical outcomes for patients with CD, as well as the importance of treatment at a specialized center with an experienced surgeon.”

Of note, the authors point out the study’s limitations, including the lack of information of dosing, duration of treatment in patients subjected to pharmacotherapy, the unknown remission status at the most recent follow-up in 21 percent of the patients, and possible inconsistencies in the group, precluding accurate representation of the general CD population.