Surgery favored over radiation to treat recurrent Cushing’s disease
Study into outcomes for 723 patients given one of three alternative treatments
People with recurrent Cushing’s disease who are treated with surgery are more likely to go into remission than patients given radiation therapy, a review study has found.
“Based on the results of the current study, surgery should be considered as a second-line treatment for recurrent [Cushing’s disease] patients as a safe method with higher remission rate with a low rate of complications,” the researchers wrote.
The study, “Recurrent Cushing’s disease: An extensive review on pros and cons of different therapeutic approaches,” was published in the journal World Neurology.
Cushing’s disease can reoccur in up to 25% of patients after initial treatment
Cushing’s disease is caused by a tumor in the brain’s pituitary gland. The pituitary tumor releases high levels of a signaling molecule called adrenocorticotropic hormone (ACTH), which triggers the adrenal glands, located just above the kidneys, to produce high levels of the stress hormone cortisol. Excessive cortisol levels give rise to typical Cushing’s symptoms.
The standard first-line treatment for Cushing’s disease is surgery to remove the pituitary tumor, which leads to disease remission in up to 90% of the cases. Disease recurrence, a phenomenon in which symptoms reappear months or years after surgery, is estimated to affect up to 25% of these patients.
Several treatment options exist for recurrent Cushing’s disease: patients can undergo another pituitary surgery, get radiation therapy on the pituitary tumor, take medications to control cortisol levels, or, in some extreme cases, undergo surgery to remove the adrenal glands.
A team of scientists in the U.S. and Iran conducted a review study and meta-analysis to assess the outcomes of these different treatment options for recurrent Cushing’s disease. In a meta-analysis, scientists pool data from multiple published studies and analyze it collectively.
Of note, the researchers focused on patients with recurrent Cushing’s, in whom symptoms initially disappear (remission) but then come back. Patients with persistent disease, in whom symptoms do not disappear after an initial surgery, were not included.
“In most studies, the outcome of the second treatment for persistent and recurrent [Cushing’s disease] is reported together. Such a system could cloud clinical judgment because the two courses of [Cushing’s disease] represent different situations with inherent complexities and therefore need to be reviewed independently,” the researchers wrote. “This study is the first meta-analysis comparing all therapeutic interventions currently used in clinical practice only for recurrent [Cushing’s disease].”
Their analysis included data from 723 people with recurrent Cushing’s across 61 studies, all of which were published between 2000 and 2021. Among these 723 patients, 499 underwent a second pituitary surgery, while 189 were given radiation therapy, and 35 were treated with medications.
The rate of remission following radiation therapy was 57%, 65% after surgery, and 75% following medical treatment. Statistical tests showed that the likelihood of remission was significantly lower for radiation therapy compared with the other two treatment approaches.
Surgery likely ‘most promising’ approach given remission and complication rates
Results suggest that a second pituitary surgery “should be considered as the most promising therapeutic modality in terms of remission rate,” the researchers wrote.
While the remission rate for patients given medical treatment was numerically higher, “the interpretation of the clinical efficiency of [medical treatment] must be cautious” due to the small number of patients included in the analysis, the researchers noted. They highlighted a need for further studies to assess medication’s effectiveness compared with surgery and radiation in recurrent Cushing’s patients.
Researchers also analyzed rates of well-documented complications with pituitary-targeting treatments: diabetes insipidus, a condition marked by excessive urination and extreme thirst due to a fluid imbalance, and hypopituitarism, marked by the pituitary gland failing to produce one or more hormones, which can arise from damage to the gland.
Diabetes insipidus was somewhat more common in patients who underwent surgery, while hypopituitarism was a bit more common in those treated with radiation therapy, results showed. However, the rate of complications did not significantly differ between these two treatments.
Although including data from many studies was a strength in this analysis, researchers noted that there was variation among studies in important factors like follow-up time and the criteria used to determine disease remission. Another limitation was that most included studies only assessed one type of treatment, rather than comparing them.
Nevertheless, the team noted that surgery should be considered a second-line treatment for Cushing’s patients who experience disease recurrence, since it’s a safe procedure associated with a relatively high remission rate and a low rate of complications.
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