Locating tumors by IPSS may not lead to better surgery outcomes

Invasive test 70% accurate, but not linked to Cushing's remission: Analysis

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Accurately locating tumors in the brain’s pituitary gland by inferior petrosal sinus sampling or IPSS — an invasive test that’s been considered the gold standard for diagnosing Cushing’s disease — may not necessarily lead to better outcomes after surgery, according to a new meta-analysis.

While IPSS correctly determined tumor location — called lateralization — within the pituitary gland in nearly 70% of cases, this was not linked to remission, or to a cure. Remission is considered in Cushing’s when signs and symptoms of the disease have disappeared.

“These findings bring into question the utility of IPSS tumor lateralization in the context of preoperative planning and surgical approach rather than confirming a pituitary source [for Cushing’s disease],” the researchers wrote.

The meta-analysis, “Inferior petrosal sinus sampling (IPSS) tumor lateralization and the surgical treatment of Cushing’s disease: a meta-analysis and systematic review,” was published in the journal World Neurosurgery.

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Cushing’s disease is caused by a pituitary adenoma, a tumor that forms in the pituitary gland, located at the base of the brain. Among other hormones, the pituitary gland releases adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands, situated atop the kidneys, to produce cortisol.

A pituitary adenoma, however, can release too much ACTH, causing cortisol to rise to excessive levels in the body. This can lead to a wide array of symptoms, ranging from weight gain and fat accumulation in certain parts of the body to high blood pressure and and high blood sugar levels.

The first-line treatment usually recommended for Cushing’s disease is the surgical removal of the pituitary adenoma. Knowing its location can help guide plans for surgery. However, some tumors are too small to find on MRI scans and may be missed.

“It is then reasonable to conclude that correct IPSS tumor localization facilitates surgical planning and resection, leading to better clinical outcomes than if IPSS tumor localization is erroneous or inconclusive,” the researchers wrote.

IPSS is an invasive test that’s used to measure ACTH levels in both the left and right sinuses (vein channels) that drain blood and other fluids from the pituitary gland.

“A gradient between the sinuses may be established to determine the tumor lateralization adjacent to the pituitary gland,” the researchers wrote.

In this study, the team sought to assess the potential benefit of locating tumors by IPSS — specifically, “to determine whether accurate inferior petrosal sinus sampling (IPSS) tumor lateralization is associated with improved clinical outcomes following the surgical treatment of Cushings disease.”

To that end, the researchers analyzed data from 17 studies that included a total of 461 children and adults with a diagnosis of Cushing’s disease. About 75% of the patients were female.

IPSS correctly determined tumor lateralization in 69% of the cases. Over a mean follow-up of 59 months, or nearly five years, remission or a cure were achieved in 78% of cases after surgical removal of the pituitary adenoma.

In seven studies where MRI data were available for a total of 137 patients, tumor lateralization determined by IPSS was consistent with MRI data in 53% of cases. The rate of correct tumor lateralization did not distinguish patients who had a pituitary adenoma visible on an MRI scan versus those who didn’t (57% vs. 69%).

There was no significant link between the rate of correct tumor lateralization and the rate of remission or a cure after surgical removal of the pituitary adenoma. Similar findings were observed when looking at data from adults and children separately.

“Limited published data suggest that IPSS lateralization may not be positively associated with postoperative remission following surgical treatment of Cushing’s disease,” the researchers wrote.

Taking the risks, success rates, and described [lack of association] between tumor lateralization and postoperative endocrinologic outcomes [into account], this work suggests that there may be limited rationale to perform … IPSS for the sole purpose of tumor localization.

Given these findings, the team questioned the use of the invasive test only for locating pituitary tumors.

“Taking the risks, success rates, and described [lack of association] between tumor lateralization and postoperative endocrinologic outcomes [into account], this work suggests that there may be limited rationale to perform … IPSS for the sole purpose of tumor localization,” the researchers wrote.

More research is needed, the scientists said.

“These findings highlight the need for rigorous studies to further characterize the postoperative benefits/disadvantages of IPSS tumor lateralization in relation to surgical methodology, treatment, and outcomes,” the team wrote.