Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America
-
Carolina Silva
Abstract
Objectives
Adrenal insufficiency (AI) is a life-threatening condition where an accurate diagnosis is critical. While the ACTH stimulation test is the diagnostic test of choice, there remains uncertainty around its protocols and interpretation of results. In this context, the objective of this study was to understand practices of North American pediatric endocrinology providers on the diagnosis of AI in children.
Methods
An anonymous electronic survey was sent to members of the Pediatric Endocrine Society.
Results
A total of 221 participants were included. The majority practiced in academic centers (78%). All respondents ordered ACTH stimulation tests. While 85% used high-dose ACTH stimulation tests (HDST) to diagnose primary AI, there was less consistency in the choice of tests (HDST vs. low-dose ACTH stimulation test; LDST) when diagnosing secondary AI. When interpreting results, 95% used peak cortisol levels, 70% considered the clinical picture, and 49% used relative increase in cortisol levels. Median (IQR) cortisol cutoff level after ACTH stimulation test that was considered sufficient was 18 (15.5–18) μg/L [496 (428–496) nmol/L]; 17% used different cutoffs for LDST, and 18% used different cutoffs for newborns. Finally, 47% were unaware of the assay that was used in their institution for cortisol measurements.
Conclusions
Pediatric endocrinology providers use ACTH stimulation tests variably, including in the choice between HDST vs. LDST, test protocols, and interpretation of results.
-
Research funding: None declared.
-
Author contributions: All authors participated in the design of the study. Trisha Patel led the design and delivery of the survey. Carolina Silva performed the data analysis, supervised by Carol Lam and Trisha Patel. All authors contributed substantially to writing the body of the manuscript. All authors read and approved the final version. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Ethical approval: The survey was approved by the Research Privacy Advisor (Provincial Health Services Authority). Ethics review was not required.
References
1. Bornstein, SR, Allolio, B, Arlt, W, Barthel, A, Don-Wauchope, A, Hammer, GD, et al.. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016;101:364–89. https://doi.org/10.1210/jc.2015-1710.Search in Google Scholar PubMed PubMed Central
2. Kazlauskaite, R, Evans, AT, Villabona, CV, Abdu, TA, Ambrosi, B, Atkinson, AB, et al.. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245–53. https://doi.org/10.1210/jc.2008-0710.Search in Google Scholar PubMed
3. Dorin, RI, Qualls, CR, Crapo, LM. Diagnosis of adrenal insufficiencyErratum in. Ann Intern MedAnn Intern Med 2003;139:194–204. https://doi.org/10.7326/0003-4819-139-3-200308050-00009. Erratum in: Ann Intern Med. 2004;140(4):315.Search in Google Scholar PubMed
4. Ng, SM, Agwu, JC, Dwan, K. A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children. Arch Dis Child 2016;101:847–53. https://doi.org/10.1136/archdischild-2015-308925.Search in Google Scholar PubMed
5. El-Farhan, N, Pickett, A, Ducroq, D, Bailey, C, Mitchem, K, Morgan, N, et al.. Method-specific serum cortisol responses to the adrenocorticotrophin test: comparison of gas chromatography-mass spectrometry and five automated immunoassays. Clin Endocrinol 2013;78:673–80. https://doi.org/10.1111/cen.12039.Search in Google Scholar PubMed
6. Kline, GA, Buse, J, Krause, RD. Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay. Clin Biochem 2017;50:475–80. https://doi.org/10.1016/j.clinbiochem.2017.02.008.Search in Google Scholar PubMed
7. Gill, H, Barrowman, N, Webster, R, Ahmet, A. Evaluating the low-dose ACTH stimulation test in children: ideal times for cortisol measurement. J Clin Endocrinol Metab 2019;104:4587–93. https://doi.org/10.1210/jc.2019-00295.Search in Google Scholar PubMed
8. Ahmet, A, Rowan-Legg, A, Pancer, L, Canadian Paediatric Society, Canadian Pediatric Endocrine Group. Community Paediatrics Committee. Adrenal suppression from exogenous glucocorticoids: recognizing risk factors and preventing morbidity. Paediatr Child Health 2021;26:242–7. https://doi.org/10.1093/pch/pxab015.Search in Google Scholar PubMed PubMed Central
9. Chabre, O, Goichot, B, Zenaty, D, Bertherat, J. Epidemiology of primary and secondary adrenal insufficiency: prevalence and incidence, acute adrenal insufficiency, long-term morbidity and mortality. Ann Endocrinol 2017;78:490–4. https://doi.org/10.1016/j.ando.2017.10.010.Search in Google Scholar PubMed
10. Mazziotti, G, Formenti, AM, Frara, S, Roca, E, Mortini, P, Berruti, A, et al.. Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects. Eur J Endocrinol 2017;177:R231–48. https://doi.org/10.1530/EJE-17-0154.Search in Google Scholar PubMed
11. Hindmarsh, PC, Honour, JW. Letter to the editor: “evaluating the low-dose ACTH stimulation test in children: ideal times for cortisol measurement”. J Clin Endocrinol Metab 2020;105:dgaa009. https://doi.org/10.1210/clinem/dgaa009.Search in Google Scholar PubMed
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- One half-century of advances in the evaluation and management of disorders of bone and mineral metabolism in children and adolescents
- Original Articles
- Safety and user experience with off-label use of a flash glucose monitor (FreeStyle Libre® 1) among very young children with type 1 diabetes mellitus
- Sonic hedgehog N-terminal level correlates with adiponectin level and insulin resistance in adolescents
- Elevated amylase and lipase levels in patients with DKA followed in the pediatric intensive care unit
- The relationship between alexithymia, health literacy, and diet quality in obese adolescents
- The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome
- Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries
- Comparative characteristics of developing morphofunctional features of schoolchildren from different climatic and geographical regions
- Leucine tolerance in children with MSUD is not correlated with plasma leucine levels at diagnosis
- Outcomes of children with severe diabetic ketoacidosis managed outside of a pediatric intensive care unit
- Thiamine status during treatment of diabetic ketoacidosis in children – tertiary care centre experience
- Premature adrenarche in Prader–Willi syndrome is associated with accelerated pre-pubertal growth and advanced bone age
- Short Communication
- Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America
- Case Reports
- Pediatric growth hormone and prolactin-secreting tumor associated with an AIP mutation and a MEN1 variant of uncertain significance
- Two cases of MEGDHEL syndrome diagnosed with hyperammonemia
- Hyperinsulinism–hyperammonemia syndrome in two Peruvian children with refractory epilepsy
- A case report of a young boy with low renin and high aldosterone levels induced by Liddle syndrome who was previously misdiagnosed with primary aldosteronism
- Adolescents with type 1 diabetes vs. hybrid closed loop systems: a case series of patients’ behaviour that challenges the algorithm.
Articles in the same Issue
- Frontmatter
- Review
- One half-century of advances in the evaluation and management of disorders of bone and mineral metabolism in children and adolescents
- Original Articles
- Safety and user experience with off-label use of a flash glucose monitor (FreeStyle Libre® 1) among very young children with type 1 diabetes mellitus
- Sonic hedgehog N-terminal level correlates with adiponectin level and insulin resistance in adolescents
- Elevated amylase and lipase levels in patients with DKA followed in the pediatric intensive care unit
- The relationship between alexithymia, health literacy, and diet quality in obese adolescents
- The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome
- Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries
- Comparative characteristics of developing morphofunctional features of schoolchildren from different climatic and geographical regions
- Leucine tolerance in children with MSUD is not correlated with plasma leucine levels at diagnosis
- Outcomes of children with severe diabetic ketoacidosis managed outside of a pediatric intensive care unit
- Thiamine status during treatment of diabetic ketoacidosis in children – tertiary care centre experience
- Premature adrenarche in Prader–Willi syndrome is associated with accelerated pre-pubertal growth and advanced bone age
- Short Communication
- Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America
- Case Reports
- Pediatric growth hormone and prolactin-secreting tumor associated with an AIP mutation and a MEN1 variant of uncertain significance
- Two cases of MEGDHEL syndrome diagnosed with hyperammonemia
- Hyperinsulinism–hyperammonemia syndrome in two Peruvian children with refractory epilepsy
- A case report of a young boy with low renin and high aldosterone levels induced by Liddle syndrome who was previously misdiagnosed with primary aldosteronism
- Adolescents with type 1 diabetes vs. hybrid closed loop systems: a case series of patients’ behaviour that challenges the algorithm.
