Most Cushing’s patients in remission after 2nd pituitary surgery: Study

Repeat surgery found 'reliable and safe' in recurrent Cushing's disease

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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About 80% of people with recurrent Cushing’s disease who underwent a second surgery to remove tumors from the brain’s pituitary gland achieved remission, according to a real-world study.

These findings show that repeat surgery “emerges as a reliable and safe treatment modality for residual or recurrent Cushing’s disease, offering satisfactory remission rates and minimal complications,” the researchers wrote, calling the study “one of the largest case series in the literature.”

The study, “Repeat endoscopic endonasal transsphenoidal surgery for residual or recurrent cushing’s disease: safety, feasibility, and success,” was published in the journal Pituitary.

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Cushing’s disease is caused by the production and release of excessive amounts of a signaling molecule called adrenocorticotropic hormone (ACTH) from tumors in the brain’s pituitary gland. ACTH signals the adrenal glands on top of the kidney to produce too much cortisol, ultimately leading to Cushing’s symptoms.

Surgery to remove these tumors from the pituitary gland, called transsphenoidal adenomectomy, is typically the first-line treatment for Cushing’s disease. When performed by an experienced pituitary surgeon, this type of surgery has a rate of cure or full remission of about 80% to 90%.

In the remaining cases, however, some residual tumor remains, or the disease fully recurs. And little is known about the success of a second surgery to treat recurrent Cushing’s disease.

Here, the researchers noted that “reoperating for residual or recurrent [Cushing’s disease] presents challenges due to altered surgical landmarks and scar tissue formation from previous surgeries.”

To learn more, the team, from Turkey, examined the outcomes of 56 Cushing’s disease patients who underwent 65 repeat surgeries, either due to residual disease (72.3%) or recurrence (27.7%). All of the patients were treated at the department of neurosurgery of Hacettepe University School of Medicine between 2006 and 2020.

The patients had a mean age of 37.6 years and most were women (85.7%).

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2nd surgery ‘remarkably’ leads to remission for 82.1% of patients

Blood tests taken before and one day after surgery showed that average cortisol levels fell from 18.7 to 13.4 micrograms per deciliter of blood (mcg/dL). Median ACTH levels also dropped, from 182.7 to 43.3 picograms per mL of blood (pg/mL).

Less than half of the patients (46.2%) saw their cortisol levels drop below 5 mcg/dL on the first day after surgery. The impact of surgery on cortisol or ACTH levels was similar between those with residual or recurrent disease.

Residual disease occurred less often following endoscopic versus microscopic transsphenoidal surgery (44% vs. 90%). Endoscopic surgery uses a thin, lighted tube with a tiny camera to visualize tumors, while microscopic surgery is similar to endoscopic surgery, but uses a microscope instead of an endoscope.

Following the first repeat surgery, 47 of the 56 patients (83.9%) experienced initial disease remission, while the remaining nine (16.1%) had residual tumors. Remission was maintained without the need for further surgeries in 44 of the 47 cases (93.6%). In three cases (6.4%), patients experienced recurrence and needed a third surgery.

Of the nine patients who failed to achieve remission after a second surgery, six chose to undergo a third pituitary surgery, one to receive radiotherapy, one to undergo adrenal gland removal surgery (adrenalectomy), and one to defer treatment.

Following a third surgery, four of these patients (44.4%) achieved sustained remission, while five (55.6%) still had residual disease. Overall, most of these patients (78.5%) achieved remission after undergoing repeat surgery.

Post-surgical transient diabetes insipidus, or the production of too much urine, occurred in five patients (7.6%), and became permanent in two (3%). During surgery, leakage of cerebrospinal fluid, which surrounds the brain and spinal cord, occurred in 20 operations (30.7%).

Lastly, a statistical analysis of the data showed that Cushing’s patients whose blood cortisol levels exceeded 5 mcg/dL one day after surgery were 91% less likely to achieve sustained remission.

“Our study underscores the efficacy and safety of repeat endoscopic transsphenoidal surgery in managing residual or recurrent Cushing’s disease,” the scientists wrote, noting that, “remarkably, 82.1% of patients achieved remission after their first reoperation.”