Study Recommends 2nd Surgery as an Option for Recurrent Cushing’s
Repeat transsphenoidal surgery led to 'reasonable' remission rates in China
A second transsphenoidal surgery (TSS) in Cushing’s disease patients with or without visible MRI lesions in the brain’s pituitary gland led to reasonable remission rates, a study reports.
Of 42 patients, 29 (69%) achieved immediate remission after repeated surgery, with no difference in remission rates between patients with recurrent and persistent Cushing’s. In addition, remission was not associated with detectable MRI abnormalities in the pituitary gland.
“Our findings suggest that for most patients who experience recurrent or persistent [Cushing’s disease], reoperation should be an option even with negative MRI findings,” the researchers wrote.
The study, “Reoperation for Recurrent and Persistent Cushing’s Disease without Visible MRI Findings,” was published in the Journal of Clinical Medicine.
Transsphenoidal surgery is first-line treatment for Cushing’s
Excessive production of adrenocorticotropic hormone (ACTH) due to a tumor in the pituitary gland, a pea-sized structure found at the base of the brain, is the hallmark of Cushing’s disease.
Overproduction of ACTH causes the adrenal glands — located atop the kidneys — to produce too much cortisol, triggering Cushing’s symptoms.
TSS is considered a first-line option among treatments for Cushing’s disease. It is a minimally invasive surgery to remove adenomas (benign tumors) from the pituitary gland, with a reported remission rate of 70%–90%.
However, hypercortisolism (excessive cortisol levels) persists in some patients. It also recurs in 3%–29% of patients, even among those who have been in remission for more than 10 years.
MRI scans are used to detect abnormalities in the pituitary gland. A second TSS can be considered when lesions remain visible in MRI scans after a first operation.
Yet, these imaging tests have limitations for the prognosis of patients living with Cushing’s, particularly in the context of repeated surgery, as the original TSS may alter the normal structure of the pituitary gland.
This uncertainty requires a discussion of risk factors and the necessity to repeat the surgery, especially for patients with non-visible lesions (negative) in MRI scans. Moreover, patients with recurrent or persistent hypercortisolism typically have a low incidence rate of positive MRI results.
Our findings suggest that for most patients who experience recurrent or persistent [Cushing’s disease], reoperation should be an option even with negative MRI findings
Researchers study efficacy of repeating TSS for recurrent or persistent Cushing’s
Now, researchers in China have investigated the efficacy of repeating TSS in patients with recurrent or persistent Cushing’s disease. They also determined if there was a relationship between positive MRI results and early remission.
The study included 42 patients — 27 with recurrent and 15 with persistent Cushing’s — each of whom had two surgeries by a single neurosurgeon between 2002 and 2021. All patients with recurrent disease had a definitive pituitary adenoma in MRI scan results before undergoing the first surgery, while 12 of those with persistent hypercortisolism had visible lesions.
Patients had a mean age of 44 years at the time of the second surgery. Both surgeries were separated by a median time interval of 43 months (a little over 3.5 years). After the second surgery, patients were followed for a median period of 15.5 months.
Immediate remission was seen in 29 patients (69%) after repeated surgeries.
Remission rates were higher among patients with recurrent Cushing’s than in those with persistent disease (77.8% vs. 57.1%). Yet, this difference was not considered statistically significant.
Repeated TSS was beneficial for patients with MRI scans indicating the presence of tumors in the pituitary gland before surgery and for those with persistent hypercortisolism but no clear evidence of an adenoma in MRI scans.
In the recurrent group, patients with positive MRI findings had an 88.2% remission rate, while those with negative results had a 60.0% remission rate — similar to that seen in patients with persistent disease who had visible lesions (63.6%).
Negative MRI findings before surgery were not found to be associated with lower chances of immediate remission after repeated surgery.
Most patients recovered well after the second surgery, except for one patient with persistent hypercortisolism who died from a severe intracranial infection.
Overall, these findings are similar to those of other studies.
“Immediate remission rates after reoperation for recurrence have been reported in the literature up to 87%,” the researchers wrote, noting that “negative MRI findings do not necessarily indicate the inexistence of pituitary adenomas or negative … results.”
However, further studies are required to verify the present results, they said. These should contain larger groups of patients treated with TSS and followed for longer periods of time to improve repeated surgery outcomes and determine which patients should be selected for such treatment.
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