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Evaluating Low-Dose Cosyntropin Testing for Central Adrenal Insufficiency in Pediatric Patients

April 25, 2025

A new study from the Division of Pediatric Endocrinology at UPMC Children’s Hospital of Pittsburgh evaluates the effectiveness of the low-dose cosyntropin stimulation test (LDT) in diagnosing central adrenal insufficiency (CAI) in children. The findings, published in Hormone Research in Paediatrics, are detailed in the article, Diagnostic Utility of Low-Dose Cosyntropin Stimulation Test for Central Adrenal Insufficiency.”

The study was authored by Cesare Morgante, MD; Kanthi Bangalore Krishna, MD; Erika McCann, RN; Selma Feldman Witchel, MD; Wassim Chemaitilly, MD; Luigi Garibaldi, MD; and Emir Tas, MD.

What is Central Adrenal Insufficiency and What Does it Matter?

Central adrenal insufficiency (CAI) occurs when the pituitary or hypothalamus fails to signal the adrenal glands to produce enough cortisol, often due to prolonged steroid use or underlying brain disorders. If missed, CAI can lead to life-threatening adrenal crises.

Traditionally, high-dose adrenocorticotropic hormone (ACTH) testing has been the diagnostic standard, but it may miss subtle cases in children. The study conducted by the Pediatric Endocrinology team at UPMC Children’s shows that the low-dose cosyntropin test, using a 13.5 μg/dL cortisol cutoff, matches the high-dose test in accuracy, with 90% sensitivity and specificity, offering a more sensitive and physiologic option for diagnosis.

Tailoring Care, Improving Accuracy

The low-dose cosyntropin test provides a more physiologic assessment of the pituitary-adrenal axis, making it especially useful when ACTH secretion is only partially impaired. The study also highlights the need for personalized cortisol thresholds, particularly in children with prior glucocorticoid exposure, to improve diagnostic accuracy and reduce the risk of misdiagnosis.

Clinical Takeaways

The findings support the low-dose cosyntropin test as a physiologic, efficient, and reliable method for identifying central adrenal insufficiency in children. It represents a meaningful step toward individualized, precision-focused endocrine care. These findings support the use of LDT as a practical alternative to high-dose testing, offering a physiologic and efficient approach to diagnosing central adrenal insufficiency in pediatric populations.

Reference

Morgante C, Bangalore Krishna K, McCann E, Witchel SF, Chemaitilly W, Garibaldi L, Tas E. Diagnostic Utility of Low-Dose Cosyntropin Stimulation Test for Central Adrenal Insufficiency. Horm Res Paediatr. 2025 Jan 6: 1-8. Online ahead of print.