Peak cortisol response to corticotropin-releasing hormone is associated with age and body size in children referred for clinical testing: a retrospective review.
BACKGROUND
Corticotropin-Releasing Hormone (CRH) testing is used to evaluate suspected adrenocorticotropic hormone (ACTH) deficiency, but the clinical characteristics that affect response in young children are incompletely understood. Our objective was to determine the effect of age and body size on cortisol response to CRH in children at risk for ACTH deficiency referred for clinical testing.


METHODS
Retrospective, observational study of 297 children, ages 30 days - 18 years, undergoing initial, clinically indicated outpatient CRH stimulation testing at a tertiary referral center. All subjects received 1mcg/kg corticorelin per institutional protocol. Serial, timed ACTH and cortisol measurements were obtained. Patient demographic and clinical factors were abstracted from the medical record. Patients without full recorded anthropometric data, pubertal assessment, ACTH measurements, or clear indication for testing were excluded (number remaining = 222). Outcomes of interest were maximum cortisol after stimulation (peak) and cortisol rise from baseline (delta). Bivariable and multivariable linear regression analyses were used to assess the effects of age and size (weight, height, body mass index (BMI), body surface area (BSA), BMI z-score, and height z-score) on cortisol response while accounting for clinical covariates including sex, race/ethnicity, pubertal status, indication for testing, and time of testing.


RESULTS
Subjects were 27 % female, with mean age of 8.9 years (SD 4.5); 75 % were pre-pubertal. Mean peak cortisol was 609.2 nmol/L (SD 213.0); mean delta cortisol was 404.2 nmol/L (SD 200.2). In separate multivariable models, weight, height, BSA and height z-score each remained independently negatively associated (p < 0.05) with peak and delta cortisol, controlling for indication of testing, baseline cortisol, and peak or delta ACTH, respectively. Age was negatively associated with peak but not delta cortisol in multivariable analysis.


CONCLUSIONS
Despite the use of a weight-based dosing protocol, both peak and delta cortisol response to CRH are negatively associated with several measures of body size in children referred for clinical testing, raising the question of whether alternate CRH dosing strategies or age- or size-based thresholds for adequate cortisol response should be considered in pediatric patients, or, alternatively, whether this finding reflects practice patterns followed when referring children for clinical testing.
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Suite 11NW, Philadelphia, USA.
Mary Ellen
ME
Vajravelu
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Suite 11NW, Philadelphia, USA.
Jared
J
Tobolski
Center for Biomedical Informatics, The Children's Hospital of Philadelphia, 3535 Market St, Philadelphia, PA 19104 USA.
Evanette
E
Burrows
Center for Biomedical Informatics, The Children's Hospital of Philadelphia, 3535 Market St, Philadelphia, PA 19104 USA.
Marianne
M
Chilutti
Department of Biostatistics and Epidemiology, University of Pennsylvania, 635 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021 USA.
Rui
R
Xiao
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Suite 11NW, Philadelphia, USA.
Vaneeta
V
Bamba
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Suite 11NW, Philadelphia, USA.
Steven
S
Willi
Global Innovative Pharma, Pfizer, Inc, 500 Arcola Road, Collegeville, PA 19426 USA.
Andrew
A
Palladino
The Children's Hospital of Philadelphia, Division of Rheumatology, 10103 Colket Building, 34th & Civic Center Blvd, Philadelphia, PA 19104 USA.
Jon M
JM
Burnham
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Suite 11NW, Philadelphia, USA.
Shana E
SE
McCormack
Adrenal insufficiency; Adrenal stimulation testing; Corticotropin-releasing hormone (CRH) stimulation test; Cortisol; Exogenous glucocorticoid exposure