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Commonly Used Test Appears to Overdiagnose CAI in Prader-Willi Syndrome

A first-of-its-kind study shows poor agreement between two testing methods for central adrenal insufficiency.

No consensus guidelines exist for evaluating central adrenal insufficiency (CAI) in patients with Prader-Willi syndrome, at least in part because previous studies have shown little consistency in CAI rates in that population. Different tests for CAI suggest rates as low as zero percent or as high as 60 percent.

Research led by endocrinologists at Nationwide Children’s Hospital appears to be the first to examine how two CAI tests can lead to different conclusions in the same patient – suggesting that one test may have a high false-positive rate. The findings were presented at the 10th International Meeting of Pediatric Endocrinology.

“Clinicians have a dilemma over how to screen for central adrenal insufficiency in their patients with Prader-Willi syndrome,” says Kathryn Obrynba, MD, a member of the Section of Endocrinology and the Prader-Willi Syndrome Clinic physician team at Nationwide Children’s, and lead author of the study. “That, in turn, leads to a dilemma about the need for steroid treatment during times of physical stress or illness.”

“...To avoid overdiagnosis and treatment, OMT may be the preferred method of screening for CAI...”

– Manmohan Kamboj, MD

Researchers studied 21 patients with Prader-Willi syndrome, who had not been previously diagnosed with CAI. Each completed a low-dose adrenocorticotropic hormone (ACTH) stimulation test and then a single-dose overnight metyrapone test (OMT).

The OMT directly assesses the response of the entire hypothalamic-pituitary-adrenal (HPA) axis, and therefore is ideal to evaluate central hormonal deficiencies and ACTH reserve. The low-dose ACTH stimulation test relies on indirect assessment of adrenal gland function. This test is readily available, quick, inexpensive and safe, and therefore has become the accepted method for assessing for CAI in most patients.

Twenty patients passed the OMT and one test was inconclusive, so none had evidence of CAI. In contrast, only 15 passed the ACTH stimulation test, meaning 29 percent had evidence of CAI, suggestive of a high false-positive rate.

Discrepancies in testing methods have been shown in earlier studies, but never before in the same patients, says Manmohan Kamboj, MD, chief of Endocrinology at Nationwide Children’s and senior author of the study.

“In an effort to avoid overdiagnosis and treatment, OMT may be the preferred method of screening for CAI in Prader-Willi syndrome,” she says.

Obrynba K, Hoffman R, Repaske D, Bucker J, Anglin K, Coshway L, Cazeau R, Lozano R, Pyle-Eiola A, Kamboj M. Could we be over diagnosing central adrenal insufficiency in Prader-Willi Syndrome? International Meeting of Pediatric Endocrinology; 2017 Sept 14-17; Washington, D.C.

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