Test may be ‘practical’ alternative for diagnosing Cushing’s in kids
Less expensive DDAVP test yields results comparable to CRH stimulation
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A diagnostic test using an artificial form of the naturally occurring hormone desmopressin could be a good alternative to the standard test used to diagnose Cushing’s disease in children and adolescents, according to a study.
Researchers found that the accuracy of the desmopressin stimulation test (DDAVP) was comparable to that of the standard corticotropin-releasing hormone (CRH) stimulation test, which is more expensive and is no longer manufactured in the U.S.
“The findings support the use of DDAVP as a reliable and practical alternative for diagnosing [Cushing’s disease] in children, particularly in settings where [CRH] is unavailable,” the scientists wrote. “This work addresses a critical gap in pediatric endocrinology and has the potential to improve diagnostic pathways and outcomes in this population.”
The study, “Diagnostic performance of desmopressin stimulation test in pediatric Cushing’s disease,” was published in Pituitary.
Cushing’s disease is caused by tumors in the brain’s pituitary gland. These tumors secrete excess adrenocorticotropic hormone (ACTH), which tells the adrenal glands to overproduce cortisol, ultimately leading to Cushing’s disease symptoms. A separate, rare condition called ectopic Cushing’s syndrome is caused by ACTH-secreting tumors outside the pituitary gland.
Data lacking on test’s value at diagnosing children with Cushing’s disease
Tests to diagnose Cushing’s disease involve measuring cortisol and ACTH levels in bodily fluids, as well as other assessments to pinpoint the source of ACTH.
The CRH stimulation test is a validated, minimally invasive method for distinguishing Cushing’s disease from ectopic ACTH secretion. Administering CRH will boost cortisol levels in people with an ACTH-producing pituitary tumor.
Doctors increasingly use the DDAVP stimulation test, in which a rise in ACTH and cortisol following DDAVP administration is suggestive of Cushing’s disease.
However, DDAVP’s use in children and adolescents with Cushing’s disease is limited by a lack of safety and accuracy data.
Scientists at the National Institutes of Health examined the medical records of 64 children and adolescents with confirmed Cushing’s disease. Half had undergone DDAVP, and half had been given the CRH test. The groups were matched for age, sex, and tumor size.
After DDAVP/CRH stimulation, ACTH and/or cortisol were measured in blood or via bilateral inferior petrosal sinus sampling (BIPSS). This invasive procedure measures ACTH levels in the veins draining from the pituitary gland.
The DDAVP test was considered consistent with Cushing’s disease if cortisol increased by more than 18% and ACTH by more than 33%. The CRH test was positive for Cushing’s disease if cortisol levels rose by more than 20% and ACTH by more than 35%.
The researchers measured blood responses to DDAVP/CRH at 15-minute intervals and found that cortisol levels peaked most commonly at 30 minutes in the DDAVP group and at 45 minutes in the CRH group. Peak ACTH levels most frequently occurred at 15 minutes in both groups. Overall, the median percentage change in blood cortisol was lower after DDAVP than CRH (58.2% vs. 82.3%), as was the median percentage change in blood ACTH (122% vs. 188%).
BIPSS results showed that both groups had similar post-stimulation ACTH changes and peak levels.
Using the diagnostic thresholds, the sensitivity — the ability of a test to correctly identify patients with Cushing’s disease — was similar for cortisol measurements obtained via DDAVP or CRH (96.9% vs. 93.8%). Although the sensitivity for ACTH was lower in the DDAVP group (81.3% vs. 96.9%), the difference was not statistically significant, meaning it could have arisen by chance.
Eight patients (12.5%) — six in the DDAVP group and two in the CRH group — showed a false-negative response, meaning that cortisol or ACTH levels didn’t rise sufficiently despite a confirmed Cushing’s disease diagnosis. Two patients, one in each group, had inadequate responses in both hormones and would have been misclassified as possible ectopic Cushing’s syndrome.
BIPSS sensitivity for ACTH after stimulation was lower with DDAVP than with CRH (80% vs. 100%). Three patients in the DDAVP group were misclassified; two of these had poorly developed petrosal veins, which likely limited the reliability of BIPSS.
Overall, patients tolerated the procedures without notable adverse events or complications. One patient in the CRH group reported a mild headache, which resolved within a few hours. No episodes of hyponatremia (low sodium) or venous thrombosis (blood clots in veins) were recorded.
“Although the DDAVP stimulation test demonstrates lower diagnostic accuracy compared to the CRH test, it still provides sufficient sensitivity and given its availability and lower cost, it represents a pragmatic alternative to CRH stimulation,” the scientists concluded.
