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Evaluating the Low-Dose ACTH Stimulation Test in Children: Ideal Times for Cortisol Measurement
Harpreet Gill1, Nick Barrowman2, Richard Webster2
1Department of Pediatrics, Division of Endocrinology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Insights
Testing cortisol at 15 and 60 minutes during the low-dose ACTH stimulation test (LDST) helps prevent false positive diagnoses of adrenal insufficiency (AI) in children. This approach refines timing for accurate AI diagnosis.
Area of Science:
- Pediatric Endocrinology
- Endocrinology
- Clinical Chemistry
Background:
- Central adrenal insufficiency (AI) diagnosis relies on the low-dose ACTH stimulation test (LDST).
- Current LDST protocols often use a 30-minute cortisol sampling time, but optimal timing remains debated.
Purpose of the Study:
- To identify optimal cortisol sampling times during the LDST in pediatric patients.
- To determine factors that predict the timing of peak cortisol levels in children undergoing LDST.
Main Methods:
- Retrospective chart review of LDSTs conducted between February 2014 and September 2017.
- Cortisol levels were measured at 0, 15, 30, and 60 minutes post-cosyntropin (1 μg) administration.
- Adrenal insufficiency was defined by cortisol values <18 μg/dL (500 nmol/L).
Main Results:
- Peak cortisol levels occurred at 15 minutes (19%), 30 minutes (67%), and 60 minutes (14%) in 221 pediatric patients.
- Testing at 15 or 60 minutes in addition to 30 minutes could prevent false positive LDST results.
- Omitting 15- and 60-minute samples would have misdiagnosed 9.8% of patients who passed the LDST.
Conclusions:
- While most children peak at 30 minutes, including 15- and 60-minute cortisol measurements reduces the risk of false positive LDST results.
- Glucocorticoid exposure, age, and BMI z-scores are independent predictors of peak cortisol timing.
Context:
Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common.
Objectives:
To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST.
Design:
Retrospective chart review of LDSTs between February 2014 and September 2017.
Setting:
The Children's Hospital of Eastern Ontario.
Patients:
Patients 3 months to 20 years who underwent LDSTs.
Intervention:
LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI.
Main Outcome Measures:
The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated.
Results:
A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing.
Conclusion:
Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.
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