BIPSS test with desmopressin can help detect Cushing’s disease: Study

Valuable tool for investigating ACTH-dependent Cushing’s, researchers say

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A diagnostic test utilizing desmopressin, an artificial form of a hormone that’s used to control excessive thirst and urination and prevent dehydration, can help to accurately identify Cushing’s disease, a new study reports.

The study, “Enhancing Cushing’s disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS,” was published in the journal Frontiers in Endocrinology.

Diagnosing Cushing’s disease is a complex process. The disorder is caused by a tumor in the brain’s pituitary gland, which releases high amounts of adrenocorticotropic hormone (ACTH), a signaling molecule that prompts the adrenal glands sitting atop the kidneys to produce the stress hormone cortisol. Excessive cortisol levels ultimately drive symptoms of Cushing’s.

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Main challenge in diagnosing Cushing’s disease is pinpointing its cause

However, several other conditions can also cause cortisol levels to rise. Thus, the main challenge in diagnosing Cushing’s disease is pinpointing its cause, which is an ACTH-producing pituitary tumor. Often, these tumors are so small that they don’t show up on imaging tests, even with state-of-the-art equipment.

The gold standard method for detecting an ACTH-producing pituitary tumor is bilateral inferior petrosal sinus sampling (BIPSS). This test involves sampling blood from veins draining the pituitary gland to check for excessive ACTH levels. In Cushing’s disease, ACTH levels measured in these sinuses will be higher than in the rest of the body.

BIPSS is often combined with another test in which a compound is given to enhance pituitary activity, leading to a spike in ACTH levels in people with Cushing’s disease. Usually, a hormone called corticotropin-releasing hormone is used for this purpose, but it is not available in many countries.

Another compound called desmopressin can also be used for this test, but there’s a debate among experts about whether BIPSS combined with desmopressin can be used to accurately detect Cushing’s disease.

In this study, researchers in Brazil reviewed data from 50 people who underwent BIPSS before and after stimulation with desmopressin.

Among the patients, 48 had Cushing’s disease caused by a pituitary tumor. The other two had ACTH-producing tumors in other parts of the body.

Using standard cutoffs for ACTH levels measured in the sinuses and in the rest of the body, BIPSS before stimulation correctly identified 85.1% of Cushing’s disease patients. After desmopressin stimulation, 89.6% of Cushing’s disease patients were correctly identified — three were positively identified only after desmopressin stimulation.

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Nearly all patients were correctly identified using desmopressin stimulation

An even higher proportion of Cushing’s disease patients (91.7%) were correctly identified when researchers combined positive test data from before and after desmopressin stimulation. Notably, the two patients who did not have Cushing’s disease still retained their negative results.

Importantly, all patients who responded to desmopressin stimulation did so within a short period of five minutes.

“Our data recommend the use of stimulation with desmopressin in the BIPSS in the differential diagnosis of ACTH-dependent [Cushing’s syndrome],” the researchers wrote.

In additional statistical tests, the researchers found that, using a different set of cutoffs, they could accurately identify 97.9% of patients who had Cushing’s disease and those who didn’t. But the team said these findings should be interpreted cautiously since there were few patients who did not have Cushing’s disease.