Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
-
Sara M. F. S. Mosca
,
Tiago S. Santos
,
Ana C. B. Mendes
Abstract
Background
Adrenal insufficiency (AI) is a life-threatening condition caused by an impaired secretion of the adrenal glucocorticoid and mineralocorticoid hormones. It comprises a heterogeneous group of primary, secondary and acquired disorders. Presentation differs according to the child’s age, but it usually presents with nonspecific and insidious symptoms and signs. The main purpose of this study was to describe and compare patients with primary or secondary AI.
Methods
Retrospective analysis of all patients with adrenal insufficiency followed at the Pediatric Endocrinology Unit in a tertiary care Portuguese hospital over the last 30 years. Data on family history, age at the first manifestation and at etiological diagnosis, and clinical presentation (symptoms, signs and laboratory evaluation) was gathered for all patients.
Results
Twenty-eight patients with AI were included; 67.9% were male, with a median (25th–75th percentile, P25–P75) age of 1 (0.5–36) month at the first presentation. The principal diagnostic categories were panhypopituitarism (42.9%) and congenital adrenal hyperplasia (25%). The most frequent manifestations (75%) were vomiting and weight loss. They were followed for a median (P25–P75) period of 3.5 (0.6–15.5) years. In respect to neurodevelopmental delay and learning difficulties, they were more common in the secondary AI group.
Conclusions
Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population, and clinicians must have a high index of suspicion. An early identification of AI can prevent a potential lethal outcome, which may result from severe cardiovascular and hemodynamic instability.
-
Research funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
-
Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Charmandari, E, Nicolaides, NC, Chrousos, GP. Adrenal insufficiency. Lancet 2014;383:2152–67, https://doi.org/10.1016/s0140-6736(13)61684-0.Search in Google Scholar
2. Chabre, O, Goichot, B, Zenaty, D, Bertherat, J. Group 1. 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
3. Rushworth, RL, Torpy, DJ, Stratakis, CAFH. Adrenal crises in children: perspectives and research directions. Horm Res 2018;89:341–51, https://doi.org/10.1159/000481660.Search in Google Scholar
4. Hsieh, S, White, PC. Presentation of primary adrenal insufficiency in childhood. J Clin Endocrinol Metab 2011;96:925–8, https://doi.org/10.1210/jc.2011-0015.Search in Google Scholar
5. Ventura, M, Serra-Caetano, J, Cardoso, R, Dinis, I, Melo, M, Carrilho, F, et al.. The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience. J Pediatr Endocrinol Metab 2019;32:721–6, https://doi.org/10.1515/jpem-2019-0030.Search in Google Scholar
6. Auron, M, Raissouni, N. Adrenal Insufficiency. NeoReviews 2015;36:92–103, https://doi.org/10.1542/pir.36-3-92.Search in Google Scholar
7. Grossman, AB. The diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab 2010;95:4855–63, https://doi.org/10.1210/jc.2010-0982.Search in Google Scholar
8. Patti, G, Guzzeti, C, Di Iorgi, N, Maria Allegri, AE, Napoli, F, Loche, S, et al.. Central adrenal insufficiency in children and adolescents. Best Pract Res Clin Endocrinol Metabol 2018;32:425–44, https://doi.org/10.1016/j.beem.2018.03.012.Search in Google Scholar
9. Bancos, I, Hahner, S, Tomlinson, J, Arlt, W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol 2015;3:216–26, https://doi.org/10.1016/s2213-8587(14)70142-1.Search in Google Scholar
10. Perry, R, Kecha, O, Paquette, J, Huot, C, Van Vliet, G, Deal, C. Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab 2005;90:3243–50, https://doi.org/10.1210/jc.2004-0016.Search in Google Scholar PubMed
11. Proust-Lemoine, E, Reynaud, R, Delemer, B, Tabarin, A, Samara-Boustani, D. Group 3: strategies for identifying the cause of adrenal insufficiency: diagnostic algorithms. Ann Endocrinol 2017;78:512–24, https://doi.org/10.1016/j.ando.2017.10.006.Search in Google Scholar PubMed
12. Wijaya, M, Huamei, M, Jun, Z, Du, M, Li, Y, Chen, Q, et al.. Etiology of primary adrenal insufficiency in children: a 29-year single-center experience. J Pediatr Endocrinol Metab 2019;32:615–22, https://doi.org/10.1515/jpem-2018-0445.Search in Google Scholar PubMed
13. Cortet, C, Barat, P, Zenaty, D, Guignat, L, Chanson, P. Group 5: acute adrenal insufficiency in adults and pediatric patients. Ann Endocrinol 2017;78:535–43, https://doi.org/10.1016/j.ando.2017.10.008.Search in Google Scholar PubMed
14. Frisch, H, Waldhauser, F, Lebl, J, Solyom, J, Hargitai, G, Kovacs, J, et al.. Congenital adrenal hyperplasia: lessons from a multinational study. Horm Res 2002;57:95–101, https://doi.org/10.1159/000058109.Search in Google Scholar PubMed
15. Engelen, M, Kemp, S, De Visser, M, Van Geel, BM, Wanders, RJA, Aubourg, P, et al.. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 2012;7:1–14, https://doi.org/10.1186/1750-1172-7-51.Search in Google Scholar PubMed PubMed Central
16. Furlan, FLS, Lemes, MA, Suguimatsu, LCF, Pires, CTF, Santos, MLSF. X-linked adrenoleukodystrophy in Brazil: a case series. Rev Paul Pediatr 2019;37:465–71, https://doi.org/10.1590/1984-0462/;2019;37;4;00015.Search in Google Scholar
17. Gupta, S, Joshi, K, Zaidi, G, Sarangi, AN, Mandal, K, Bhavani, N, et al.. Novel mutations and spectrum of the disease of NR0B1 (DAX1)-related adrenal insufficiency in Indian children. J Pediatr Endocrinol Metab 2019;32:863–9, https://doi.org/10.1515/jpem-2018-0440.Search in Google Scholar
18. Burtman, E, Regelmann, MO. Endocrine dysfunction in X-linked adrenoleukodystrophy. Endocrinol Metab Clin N Am 2016;45:295–309, https://doi.org/10.1016/j.ecl.2016.01.003.Search in Google Scholar
19. Duro, IP, Mosca, S, Araújo, G, Lorenzo, J, Freitas, J, Oliveira, MJ, et al.. Neonatal adrenal insufficiency – beyond the common causes. J. Pediatr. Neonatal. Individ. Med. 2022;11:7–11.Search in Google Scholar
20. Bergthorsdottir, R, Leonsson-Zachrisson, M, Odén, A, Johannsson, G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab 2006;91:4849–53, https://doi.org/10.1210/jc.2006-0076.Search in Google Scholar
21. Ekman, B, Fitts, D, Marelli, C, Murray, RD, Quinkler, M, Zelissen, PMJ. European adrenal insufficiency registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy. BMC Endocr Disord 2014;14:40, https://doi.org/10.1186/1472-6823-14-40.Search in Google Scholar
22. Shulman, DI, Palmert, MR, Kemp, SF. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics 2007;119:e484–94, https://doi.org/10.1542/peds.2006-1612.Search in Google Scholar PubMed
23. 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
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
Articles in the same Issue
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
