Revisiting peak serum cortisol response to insulin-induced hypoglycemia in children
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ORIGINAL ARTICLE
Revisiting peak serum cortisol response to insulin‑induced hypoglycemia in children J. B. Drummond1,2 · B. S. Soares1 · W. Pedrosa2 · A. Ribeiro‑Oliveira Jr.1 Received: 31 July 2020 / Accepted: 14 September 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Purpose To evaluate factors that could potentially affect the hypothalamic-pituitary adrenal (HPA) axis response to insulininduced hypoglycemia in children without history or symptoms of adrenal insufficiency and to propose a cut-off value to define a normal response in this population. Methods Exploratory single-center study involving 78 children that prospectively underwent insulin tolerance test (ITT) for suspected growth hormone (GH) deficiency. Methods Glucose, cortisol, GH, adrenocorticotrophic hormone (ACTH), epinephrine and norepinephrine levels were measured at baseline and after insulin-induced hypoglycemia. Serum cortisol was measured using Access automated immunoassay. Results Mean (range) basal morning serum cortisol of 8 (2.2–19.5) µg/dL/222 (61–542) nmol/L increased after hypoglycemia to 20.5 (14.6–29.5) µg/dL/570 nmol/L (405–819) nmol/L. Peak serum cortisol levels of 14.6 µg/dL (405 nmol/L) and 15.4 µg/dL (428 nmol/L) corresponded to the 2.5th and 5th percentiles, respectively. Peak serum cortisol correlated with peak plasma epinephrine (r = 0.367; P = 0.0014) but did not correlate with age, BMI-SD or peak serum GH. Children with intact and abnormal GH responses presented similar mean peak serum cortisol levels (20.0 vs. 20.6 µg/dL/555 vs. 572 nmol/L; P = 0.21). Conclusion Our data indicate that the current cut-off to define normal HPA axis response in children after insulin-induced hypoglycemia warrants reevaluation to avoid over-diagnosis of adrenal insufficiency. Our results suggest that peak serum cortisol levels ≥ 15.4 µg/dL (428 nmol/L) in children undergoing ITT might represent a normal cortisol response to stress, regardless of age, BMI or GH secretory capacity. Keywords Insulin-tolerance test · Hypoglycemia · HPA axis · Children
Introduction The insulin tolerance test (ITT) is considered the goldstandard diagnostic tool for evaluation of GH secretory capacity and the hypothalamic–pituitary–adrenal (HPA) axis [1, 2]. In clinical practice, ITT is mostly used for the evaluation of children and adolescents with short stature when anthropometric, radiological and baseline laboratory parameters suggest GH deficiency [3]. Peak GH response to * A. Ribeiro‑Oliveira Jr. [email protected] 1
Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais 30130‑100, Brazil
Hermes Pardini Institute, Belo Horizonte, Minas Gerais, Brazil
2
hypoglycemia is then evaluated according to pre-defined cutoff levels which may differ among various immunoassays [4]. Concomitant assessment of the HPA axis is frequently performed in patients undergoing ITT to rule out potential associated central adrenal insufficiency [5]. In addition, the hypoglycaemic stress
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