‘Practical’ desmopressin test seen to help diagnose Cushing’s disease
Noninvasive way of distinguishing the disease from ectopic Cushing’s supported
A diagnostic test using desmopressin, an artificial form of a naturally occurring hormone, can help to accurately identify people with Cushing’s disease, a study reports.
Easier than the current gold standard for diagnosing this disease, the desmopressin stimulation test might “reduc[e] the reliance on invasive procedures and provid[e] a practical solution for managing complex cases,” its researchers wrote.
The study, “Diagnostic Accuracy of the Desmopressin Stimulation Test in the Comprehensive Assessment of ACTH-Dependent Cushing’s Syndrome: A Comparative Analysis with BIPSS and TSS,” was published in the journal Endocrine Research.
Petrosal sinus sampling is gold standard for diagnosing Cushing’s disease
Cushing’s syndrome refers to a group of disorders characterized by excessive levels of the hormone cortisol.
The specific cause of Cushing’s disease is an abnormal increase in cortisol due to tumors in the pituitary gland that produce and release too much adrenocorticotropic hormone (ACTH), another hormone that promotes cortisol production. ACTH-producing tumors found outside the pituitary gland can lead to a rarer form of Cushing’s, known as ectopic Cushing’s syndrome.
To distinguish Cushing’s disease from ectopic Cushing’s, imaging tests like MRI can be used. However, in many cases, small tumors within or outside the pituitary gland may not be visible on imaging scans. As such, a “comprehensive biochemical assessment is essential to identify the underlying cause of excessive ACTH production,” the researchers wrote.
Bilateral inferior petrosal sinus sampling, or BIPSS, is considered a gold standard, the most reliable diagnostic tool for distinguishing between the two conditions, especially for patients with inconclusive imaging or biochemical results. It entails measuring ACTH levels in blood collected from the veins draining the pituitary gland.
But BIPSS is an invasive procedure that comes with significant radiation exposure, and its availability is limited to certain countries, the study noted.
“Alternatively, an approach combining dynamic tests and imaging in a multidisciplinary team can also be advantageous,” the scientists wrote. “This approach is relatively simpler, less complex, and more cost-effective than BIPSS, potentially reducing the need for BIPSS in certain cases.”
Giving desmopressin leads to higher ACTH or cortisol levels in patients
A desmopressin stimulation test (DST) has been proposed as a useful tool to distinguish Cushing’s disease from ectopic Cushing’s. This diagnostic test involves administering desmopressin — a lab-made version of the naturally occurring hormone that causes ACTH or cortisol levels to rise in people with Cushing’s disease, but generally not in those with ectopic Cushing’s.
Researchers in Iran evaluated the test’s value in distinguishing between people with different forms of ACTH-dependent Cushing’s syndrome.
Their study involved 23 patients with a mean age was 38.9, most of whom were women (78%). All underwent DST, BIPSS, and transsphenoidal adenomectomy, a standard surgical procedure used to remove pituitary tumors. Ultimately, 21 patients were diagnosed with Cushing’s disease and two with ectopic Cushing’s.
Two definitions for a positive DST result indicating the presence of Cushing’s disease were used. One was a post-desmopressin stimulation increase of at least 30% for ACTH or 20% for cortisol, while the other required a rise of at least 30% for ACTH and 20% for cortisol.
DST demonstrated robust sensitivity, correctly identify Cushing’s disease in patients already diagnosed as such by BIPSS: 90% under the first definition, and 76.2% under the second.
The positive predictive value — the probability of having a positive result for Cushing’s disease on BIPSS among those testing positive via DST — was also high: 95% under definition one and 94.1% under definition two.
Test shows ‘promise in accurately identifying’ disorder’s underlying cause
Conversely, the negative predictive value was 33.3% and 16.7% under the definitions, respectively, “suggesting that a negative result in the DST might not completely exclude the possibility of pituitary-dependent [Cushing’s syndrome],” the researchers wrote. Of note, the negative predictive value refers to the probability of having a negative result for Cushing’s disease on BIPSS among those testing negative for the condition on DST.
Compared with a transsphenoidal adenomectomy (TSS), DST showed good sensitivity in detecting Cushing’s disease: 90.9% under definition one and 77.3% under definition two. The positive predictive values under both definitions reached 100%, “indicating that a positive result in the DST was exceptionally accurate in identifying pituitary-dependent [Cushing’s syndrome] among the patients,” the team wrote.
As with BIPSS, the negative predictive value for DST against TSS was 33.3% under the first definition and 16.7% under the second.
No serious adverse events were reported following the DST and BIPSS.
“The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent [Cushing’s syndrome],” the scientists wrote. “Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.”
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