Dexamethasone suppression failed to help detect tumors in Cushing’s

No improvement seen in finding pituitary tumors on PET scans in study

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Dexamethasone suppression did not improve the detection of pituitary tumors via the use of PET, or positron emission tomography, scans in adults with Cushing’s disease, a new study has found.

In most cases, using imaging tests to determine tumor location before pituitary surgery — the first-line treatment for Cushing’s disease — helps improve the procedure’s efficacy. Dexamethasone, which is used as a diagnostic tool in Cushing’s, was thought to improve the ability of these imaging tests to determine tumor location.

Evidence supporting this assumption was not found, however, in this study by researchers at Yonsei University College of Medicine, in South Korea.

“This study is important for increasing the effectiveness of PET using [dexamethasone],” the scientists wrote.

Titled “Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors,” the study was published in the journal Cancer Imaging.

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Double pituitary tumors detected in up to 13% of Cushing’s patients

Disease remission as high as 90%-100% when tumor location is known

Cushing’s disease is marked by high levels of the hormone cortisol due to the presence of a tumor in the brain’s pituitary gland. These tumors, called adenomas, cause the pituitary gland to produce and release too much adrenocorticotropic hormone, or ACTH. This signaling molecule triggers the adrenal glands, which sit atop the kidneys, to produce excess cortisol.

A first-line or common initial treatment for Cushing’s disease is transsphenoidal adenomectomy, a surgical procedure used to remove disease-causing tumors from the pituitary gland.

When tumor location is known before surgery, disease remission rates can reach as high as 90%-100%. However, remission rates can drop to about 50%-60% when surgeons operate without knowing the exact location of the tumor.

An increased uptake of a radioactive tracer agent called 18 F-fluorodeoxyglucose (18F-FDG) in ACTH-producing pituitary tumors has been observed in PET scans. This agent is used to identify sites of abnormal glucose or blood sugar metabolism, such as those found in malignant cancers. As such, 18F-FDG may help physicians to localize, or determine the location of, disease-causing tumors before surgery.

Recent studies showed that corticotropin-releasing hormone (CRH) selectively increases glucose uptake in pituitary tumors, enhancing tumor detection on 18F-FDG PET scans.

Now, a team of researchers in Seoul hypothesized that dexamethasone suppression also might enhance the detection of pituitary tumors before surgery.

Normally, taking dexamethasone — a lab-made steroid similar to cortisol — suppresses the release of ACTH from the pituitary gland, leading to a marked drop in cortisol production by the adrenal glands. With ACTH-producing tumors that do not respond to dexamethasone, cortisol levels remain high, signaling the presence of Cushing’s.

“FDG uptake of corticotrophic adenomas is less suppressed than that of normal pituitary glands after [dexamethasone] suppression due to glucocorticosteroid resistance,” the researchers wrote. Glucocorticosteroid resistance refers to the body’s inability to respond to hormones like cortisol.

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No difference in detection with or without dexamethasone suppression

To test their hypothesis, the team analyzed data from 22 adults with Cushing’s disease. After diagnosis, but before surgery, all of the patients underwent two rounds of 18F-FDG PET, before and after dexamethasone suppression, followed by a pituitary MRI scan.

After surgery, immediate remission — defined as cortisol levels dropping blow 1.8 micrograms per deciliter (mcg/dL) within seven days — was achieved in 18 patients (81.8%). Delayed remission, or low cortisol within six months, occurred in three patients (13.6%), while one (4.6%) showed no response.

Among the pituitary tumors successfully localized by PET after dexamethasone suppression, the mean standardized uptake value (SUV) of 18F-FDG did not change from before or after dexamethasone compared with normal pituitary glands. Dexamethasone did increase the maximum SUV value, but the difference was not statistically significant.

Higher 18F-FDG uptake was seen in tumors measuring more than 5 millimeters compared with the surrounding tissue, but dexamethasone suppression did not affect these results.

MRI successfully located 90.9% of pituitary tumors, while inferior petrosal sinus sampling — an invasive method to detect ACTH-producing tumors — successfully found 84.6% of tumors in the 13 patients with available data.

In the first round of PET scans, pituitary tumors were visible in 17 scans and not in five, as assessed by specialists. A consensus that the tumor was evident in two scans was reached, but these clinicians disagreed on the exact location. After dexamethasone suppression, tumors were detected in 16 scans and not identified in five. Specialists disagreed on the presence location of tumors in only one case.

Agreement on tumor location between specialists was 87.2% before dexamethasone and 93.8% after, “confirming excellent interobserver agreements, and the result was judged reliable,” the team wrote.

“Among the instances where both opinions agreed, there were no lesions that showed differences in visibility between scans before and after [dexamethasone] administration,” the researchers wrote, adding that “this meant that lesions were either consistently visible or invisible in both scenarios.”

Overall, study findings indicated that “[dexamethasone] suppression did not improve the localization of 18F-FDG PET/CT in patients with [Cushing’s disease],” the team wrote.