CVS May Aid in Cushing’s Diagnosis When MRI Scans Are Negative

Central venous sampling 'reliable' when pituitary tumors not detected on scans

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A minimally invasive procedure called central venous sampling (CVS) may help in the diagnosis of Cushing’s disease in people with a disease-causing pituitary tumor that is not detected by MRI scans, a study suggests.

CVS, which measures the levels of the adrenocorticotropic hormone (ACTH) from the brain’s pituitary gland, can be used in such cases to confirm a Cushing’s disease diagnosis, the researchers found.

“In our study, the accuracy in the [use] of CVS was found to be as high as that of MRI,” the team wrote, adding that, in cases with “MRI-negative pituitary [tumors], it can be a reliable procedure” for diagnosing Cushing’s.

The study, “Central venous sampling and magnetic resonance imaging in the diagnosis of ACTH-dependent Cushing’s syndrome,” was published in The Neuroradiology Journal.

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People with endogenous Cushing’s syndrome have excess cortisol levels in the body. The most common cause is a pituitary adenoma — a tumor in the pituitary gland — that releases high levels of ACTH, which increases cortisol production by the adrenal glands. In this case the condition is called Cushing’s disease.

Ectopic Cushing’s syndrome occurs when ACTH-producing tumors develop outside the pituitary gland, in organs like the pancreas and the lungs. They also may arise in the thyroid and thymus glands.

Tools for a Cushing’s disease diagnosis

An MRI of the pituitary gland is often used to confirm a Cushing’s diagnosis. However, the small size of pituitary adenomas — called microadenomas — means that they may not be detected even by MRI.

Central venous sampling, or CVS for short, is a minimally invasive procedure that can distinguish endogenous from ectopic ACTH-dependent Cushing’s syndrome. For the procedure, catheters are inserted into specific veins — in this case to access both inferior petrosal veins that collect blood from certain brain areas, including the pituitary gland. Central levels of ACTH are then compared to those obtained from circulating (peripheral) blood.

The procedure can be performed with and without corticotropin-releasing hormone (CRH) stimulation. CRH promotes the release of ACTH by the pituitary gland, which in turn leads to elevated cortisol levels. In the case of CRH stimulation, ACTH is measured at baseline (before treatment) and then within two, five, and 10 minutes of administration.

A ratio of central to peripheral ACTH of more than two before CRH stimulation and greater than three after CRH stimulation is consistent with pituitary Cushing’s disease. For ectopic cases, the ratio is typically under two both before and after CRH stimulation.

In this study, researchers in Turkey evaluated the accuracy of CVS with CRH stimulation versus MRI for the diagnosis of ACTH-producing pituitary microadenomas.

Their retrospective analysis involved 29 patients with Cushing’s syndrome who underwent central venous sampling with CRH stimulation and also were examined by MRI at their hospital from January 2008 to March 2021. The patients had a median age of 38, and most (89.6%) were female.

All of them underwent transsphenoidal surgery, a minimally invasive surgical procedure to remove tumors from the pituitary gland. Cushing’s disease was then confirmed by gland tissue analysis.

A total of 24 patients had MRI scans before undergoing surgery. Scans detected a pituitary adenoma in 17 patients, while no tumor was detected in seven others. These findings meant that preoperative pituitary MRI had a sensitivity, or in other words had the ability to correctly identify those with the disease, of 70.8%.

CVS was successfully performed on 26 patients, with 23 of them (88.4%) being diagnosed with Cushing’s disease.  Two patients (7.7%) were diagnosed with ectopic ACTH syndrome and the third patient received a Cushing’s disease diagnosis only after undergoing surgery.

Central to peripheral ratios of ACTH measured at baseline were 13.42, and then within two minutes of CRH stimulation 9.61, increasing to 13.83 after five and 10.91 after 10 minutes. Overall, this meant that CVS had a 95.8% sensitivity to diagnose Cushing’s disease, which was higher than that of MRI.

Also, the negative predictive value ratio — the ratio of people who tested negative and did not actually have Cushing’s — was higher in CVS than in MRI (66% vs. 22%).

Because accurate localization of the pituitary adenoma, also called adenoma lateralization, before surgery is crucial for tumor removal, researchers compared the accuracy of both methods.

Results showed that the accuracy of CVS was as high as that of MRI (73.9% vs. 76.4%).

Overall, CVS with CRH stimulation has higher sensitivity in the localization of pituitary microadenomas than MRI scans, the researchers noted.

The findings suggest that for patients with MRI-negative pituitary microadenomas, central venous sampling can be used with similar accuracy rate as MRI, they team concluded.