An Alternative Method for Diagnosing Central Adrenal Insufficiency in Newborns

An Alternative Method for Diagnosing Central Adrenal Insufficiency in Newborns 1024 683 Mary Bates, PhD
Baby in NICU

Researchers evaluate the utility of random cortisol levels to diagnose adrenal insufficiency.

In infants with central adrenal insufficiency, adrenocorticotropic hormone (ACTH) fails to signal to the adrenal gland, leading to decreased cortisol levels. It is a potentially life-threatening condition requiring urgent diagnosis and treatment.

Diagnosing central adrenal insufficiency typically involves a low-dose synthetic ACTH (cosyntropin) stimulation test, which assesses the ability of the adrenal glands to respond to ACTH. However, this test is time- and labor-intensive and entails serial blood draws that may be excessive for newborns.

In a new study, clinician-researchers from Nationwide Children’s studied the utility of another, less complicated testing option to diagnose central adrenal insufficiency in infants: random serum cortisol levels. While research has shown that cortisol levels lack a diurnal rhythm within the first four months of life, and thus random cortisol levels drawn during this time may be useful for determining adrenal insufficiency, this finding has yet to be evaluated.

The researchers performed a retrospective chart review of about 250 infants less than four months old who underwent a low-dose cosyntropin stimulation test and had their random serum cortisol levels checked beforehand. The infants were divided into three groups: those diagnosed with central adrenal insufficiency, those at risk for central adrenal insufficiency (having abnormal MRI findings but passing the low-dose cosyntropin stimulation test), and a non-adrenal insufficiency control group.

As expected, the researchers found that random cortisol levels were significantly lower in infants with central adrenal insufficiency compared to those in the at-risk and control groups. They conclude that though random serum cortisol levels can be used to evaluate central adrenal insufficiency within the first four months of life, its value is best when done in infants less than one month of age.

“In addition, we identified a cut-off random serum cortisol level of 5.6 mcg/dL, which has 100% specificity and 42.6% sensitivity for making the diagnosis of central adrenal insufficiency in term infants less than thirty days old,” says Ayse Bulan, MD, an endocrinology fellow at Nationwide Children’s and first author of the study. “We chose this cut-off value to optimize specificity and help our clinical diagnosis.”

Dr. Bulan and colleagues say that further, prospective studies are needed to validate this cut-off value and investigate random cortisol levels in preterm infants, but this study is a promising start.

“More work is needed, but this study is important because it is the first to provide a cut-off value for random cortisol levels in infants with central adrenal insufficiency,” she says.



Bulan A, Pyle-Eilola AL, Mamilly L, Chaudhari M, Henry RK. The utility of a random cortisol level in determining neonatal central adrenal insufficiency. Clinical Endocrinology (Oxf). 2023 Jun;98(6):779-787. doi: 10.1111/cen.14903. Epub 2023 Mar 20.


About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.