Endoscopic transsphenoidal surgery safe, effective: Study

Remission 3-6 months post-surgery linked to higher rates of long-term remission

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Endoscopic transsphenoidal surgery (ETSS), a type of minimally invasive surgery to remove pituitary tumors through the nose, was found to be safe and effective for bringing about remission in Cushing’s disease, according to a study in Turkey.

In patients in whom tumors were larger and had spread into the cavernous sinuses, the hollow spaces located behind each eye socket, the rates of remission following surgery were lower.

These findings confirm “the usefulness of ETSS for the treatment of [Cushing’s disease], and highlight the importance of the size of the [tumor] and presence/absence of cavernous sinus invasion on preoperative MRI in predicting long-term remission postoperatively,” the researchers wrote.

The study, “Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease,” was published in the Journal of Korean Neurosurgical Society.

Cushing’s disease, a form of Cushing’s syndrome, is generally caused by benign tumors (adenomas) in the pituitary gland that trigger the production of  adrenocorticotropic hormone (ACTH). This hormone signals the adrenal glands to produce and release cortisol, leading to Cushing’s symptoms.

Most patients undergo ETSS to remove the pituitary tumor and achieve disease remission. However, previous studies have reported varying remission rates, between 45% and 95%, with the disease recurring or returning in 3% to 66% of the cases.

Further analyses from different clinical centers may help unveil the reasons behind this variability.

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Data from patients who had endoscopic transsphenoidal surgery

With this in mind, a team of surgeons in Turkey retrospectively analyzed data from 87 patients with Cushing’s disease who underwent ETSS at Sakura City Hospital in Istanbul between 2014 and 2022. The analysis included data gathered before and after the surgery.

Patients had a mean age of 42.2 years and most (79%) were women. They were followed for  a mean of 39.5 months (about 3.3 years).

A total of 96 surgeries were performed: 79 were first-time surgeries, six were performed for residual tumors, and 11 following disease recurrence. Eight of the 17 patients who had the surgery more than once had the previous operation at another center.

Remission was achieved between three and six months after surgery in 74 cases (77%), with long-term remission being attained in 79 cases (82%).

Patients were considered to be in remission when their cortisol levels were below 5 micrograms per deciliter (mcg/dL), or were 1.8 mcg/dL or lower after a dexamethasone suppression test conducted between three to six months after surgery and during their latest follow-up. The dexamethasone test is usually performed to confirm the presence of hypercortisolism (high cortisol levels); it measures blood cortisol levels in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks its production.

Among the 79 first-time surgeries, 62 cases (78%) of remission were achieved between three and six months. In two cases (2.5%), the tumor reappeared during follow-up, while in 60 others (97%) remission was sustained.

There were 17 cases (22%) where the disease persisted in the first six months after surgery. Remission was eventually achieved in five (29%). In two cases, remission was reached after stereotactic radiosurgery (STRS), a type of radiation therapy that uses several precise radiation beams to target tumors. In two other cases, remission was attained with medication alone, and in another with a combination of STRS and medication.

Remission achieved in 82% of patients after first surgery

At the latest follow-up visit, remission after the first surgery was seen in 65 cases (82%).

Of the 17 patients who required a second surgery, remission was achieved in 12 (71%) and long-term remission in 13 (77%). No statistically significant differences were seen regarding remission rates between three and six months in patients with one surgery or a second.

Based on MRI scans, tumors were classified according to their invasiveness into surrounding tissues using the Knosp and Hardy classifications, which are standard methods for predicting prognosis.

The analysis revealed that in the case of extended tumor invasion into the cavernous sinus, a tumor larger than 2 centimeters was linked to lower remission rates after surgery. Achieving remission between three and six months after surgery was linked to higher rates of long-term remission.

Analysis of the 96 tumors collected via ETSS showed 74% were positive for ACTH and were classified as adenomas.

Post-surgical complications were seen in 20% of the cases, with the most frequent being temporary and permanent diabetes insipidus, a condition wherein the kidneys are unable to prevent water from being eliminated. Hypopituitarism, which occurs when the pituitary gland fails to produce enough of certain hormones, occurred in 4% of the cases.

Overall, these findings suggest “ETSS is a safe and effective method for the treatment of [Cushing’s disease]. Some characteristics of adenomas, such as size, cavernous sinus invasion, and postoperative residue, may predict long-term remission,” the researchers wrote.