The utility of a random cortisol level in determining neonatal central adrenal insufficiency

Oct 3, 2026

Objectives: Establish whether a random serum cortisol (rSC) level can be useful for determining neonatal central adrenal insufficiency (CAI) in infants younger than 4 months. Design and Patients: Retrospective chart review of infants who received low-dose cosyntropin stimulation (≤4 months) with rSC as baseline cortisol, grouped as CAI, at risk (ARF-CAI), and non-CAI; mean rSC compared and ROC used for cut-off selection. Results: CAI showed lower rSC (1.98 ± 1.88 mcg/dl) versus ARF-CAI and non-CAI; ROC identified an rSC cut-off of 5.6 mcg/dl with 42.6% sensitivity and 100% specificity in term infants. Conclusions: rSC is most valuable when obtained within 30 days of life and provides a term-infant diagnostic threshold.

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CategoryHealthcare

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Abstract

Objectives

Design and Patients

Results

Conclusions

Introduction

Materials and Methods

Received: 16 December 2022 Revised: 13 February 2023 Accepted: 27 February 2023 DOI: 10.1111/cen.14903 ORI G INA L ART I CLE The utility of a random cortisol level in determining neonatal central adrenal insufficiency Ayse Bulan1 | Amy L. Pyle‐Eilola2,3 | Leena Mamilly1 | Monika Chaudhari1 | Rohan K. Henry1 1Section of Endocrinology, Department of Pediatrics, Nationwide Children's Hospital/ The Ohio State University College of Medicine, Columbus, Ohio, USA 2Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA 3Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, USA Correspondence Rohan K. Henry, Division of Endocrinology, Nationwide Children's Hospital, The Ohio State University College of Medicine, 700 Children's Dr, Columbus, OH 43205, USA. Email: [rohan.henry@nationwidechildrens.org](rohan.henry@nationwidechildrens.org) Abstract Objectives: While it has been established within the first 4 months of life that thereis no circadian rhythm, what is unclear is the usefulness of a random serum cortisol (rSC) level in determining neonatal central adrenal insufficiency (CAI) . The objective of the study is to determine the utility of using rSC in infants less than 4 months old in the evaluation of CAI. Design and Patients: Retrospective chart review of infants who underwent a low dose cosyntropin stimulation test ≤4 months of life with rSC taken as baseline cortisol before stimulation. Infants were divided into three groups: those diagnosed with CAI, those at risk for CAI (ARF‐CAI) and a non‐CAI group. Mean rSC for each group was compared, and ROC analysis was used to identify rSC cut‐off for the diagnosis of CAI. Results: Two hundred and fifty one infants with the mean age of 50 . 5 ± 38 .08 days, and 37% of these were born at term gestation. The mean rSC were lower in the CAI group (1.98 ± 1.88 mcg/dl) as compared to the ARF‐CAI (6.27 ± 5.48 mcg/dl, p = .002) and non‐CAI (4 .6 ± 4 .02 mcg/dl, p = .007) groups. ROC analysis identified a cut‐off of rSC level of 5.6 mcg/dL is associated with 42.6% sensitivity and 100% specificity for the diagnosis of CAI in term infants. Conclusions: This study demonstrates that though an rSC can be used within the first 4 months of life, its value is best when done ≤30 days of life. Moreover, a diagnostic cut‐off for CAI using rSC levels was identified for term infants. KEYWO R DS central adrenal insufficiency, cortisol, neonatal 1 | INTRODUCTION First described in 1885, as a state characterized by general languor and disability, primary adrenal insufficiency may involve pathology of the adrenal gland, is a deficiency of both glucocorticoid and mineralocorticoid. Central adrenal insufficiency (CAI) may produce similar features with the exception of salt loss and this arises from pathology of the hypothalamus or pituitary gland.1,2 Glucocorticoid exposure is the most common cause of CAI. However, outside of that, CAI rarely occurs in isolation as a single hormonal deficiency. More commonly it coexists with other pituitary hormonal deficiencies.3–5 Evaluating the integrity of the hypothalamic pituitary adrenal axis is key to making a diagnosis of CAI and testing has evolved over time. Historically, the insulin tolerance test was used in the workup of CAI; Ayse Bulan and Amy L. Pyle‐Eilola are co‐first authors. Clinical Endocrinology. 2023;98:779–[787.](787. wileyonlinelibrary.com/journal/cen)[ wileyonlinelibrary.com/journal/cen](787. wileyonlinelibrary.com/journal/cen) © 2023 John Wiley & Sons Ltd. | 779 780 | BULAN ET AL. however, it has fallen out of favour due to the potential for severe hypoglycemia and seizures, making it particularly dangerous for newborns.6,7 As a result, other tests are now being utilized: most commonly the low dose cosyntropin stimulation test. However, this test is labour‐intensive, requires serial blood draws which may be an exces

FAQs

What was the main objective of the study?

To determine the utility of random serum cortisol (rSC) levels in infants under 4 months for evaluating neonatal central adrenal insufficiency (CAI).

What cut-off value for rSC was identified for term infants, and what were its diagnostic characteristics?

For term infants, ROC analysis identified an rSC cut-off of 5.6 mcg/dl associated with 42.6% sensitivity and 100% specificity for CAI diagnosis.

What does the study conclude about when rSC is most useful?

rSC can be used within the first 4 months, but its value is best when measured at ≤30 days of life.

Oct 3, 2026

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