Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
-
Bruno Bouça
,
Andreia Nogueira
Abstract
Objectives
Polyglandular autoimmune syndromes (PAS) are characterized by the association of two or more autoimmune diseases (AID) and are classified into four types. PAS type 1 is more frequently manifested in childhood, but the prevalence of other PAS in children, less described in the literature, seems to be underestimated.
Methods
This study aimed to evaluate the prevalence of PAS in a selected pediatric population of 879 children with Diabetes mellitus type 1 (DM1), autoimmune thyroid disease (AITD), and Addison’s disease (AD) followed in our hospital for 10 years and describe and classify the manifestations of different PAS.
Results
We diagnosed 35 children with PAS, most fulfilled criteria for PAS type 3 (65.7%), and AITD was the AID more frequently detected (74.3%). PAS type 1 was not diagnosed in our sample. Patients with PAS manifested DM1 and AITD at a younger age than children with monoglandular pathology (7.7 vs. 9.3 years, p=0.04 and 7.7 vs. 13.1 years, p<0.01).
Conclusions
This is the first study that analyzes the prevalence of different types of PAS in a pediatric population followed by endocrine pathologies, namely DM1, AD, and AITD. As PAS manifestations are often preceded by a long latency period characterized by the presence of autoantibodies, we reinforce the need to value these markers for timely diagnosis and to screen PAS in patients with AD throughout their lives.
-
Research funding: None declared.
-
Author contributions: 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 local Institutional Review Board deemed the study exempt from review.
References
1. Husebye, ES, Anderson, MS, Kämpe, O. Autoimmune polyendocrine syndromes. N Engl J Med 2018;378:1132–41. https://doi.org/10.1056/nejmra1713301.Search in Google Scholar PubMed PubMed Central
2. Pham-Dobor, G, Hanák, L, Hegyi, P, Márta, K, Párniczky, A, Gergics, M. Prevalence of other autoimmune diseases in polyglandular autoimmune syndromes type II and III. J Endocrinol Invest 2020;43:1–9. https://doi.org/10.1007/s40618-020-01229-1.Search in Google Scholar PubMed PubMed Central
3. Neufeld, M, Blizzard, RM. Polyglandular autoimmune disease. In: Pinchera, A, Doniach, D, Fenzi, DF, Baschieri, L, editors. Autoimmune aspects of endocrine disorders. London, UK: Academic Press; 1980:357–65 pp.Search in Google Scholar
4. Betterle, C, Zanchetta, R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed 2003;74:9–33.Search in Google Scholar
5. Schneller, C, Finkel, L, Wise, M, Hageman, JR, Littlejohn, E. Autoimmune polyendocrine syndrome: a case-based review. Pediatr Ann 2013;42:203–8. https://doi.org/10.3928/00904481-20130426-12.Search in Google Scholar PubMed
6. Renzullo, A, Accardo, G, Esposito, D, De Bellis, A, Bizzarro, A, Romano, M. Hashimoto’s thyroiditis and entero-chromaffin-like cell hyperplasia: early detection and somatostatin analogue Treatment. Eur J Inflamm 2013;11:863–70. https://doi.org/10.1177/1721727X1301100329.Search in Google Scholar
7. Bain, A, Stewart, M, Mwamure, P, Nirmalaraj, K. Addison’s disease in a patient with hypothyroidism: Autoimmune polyglandular syndrome type 2. In: BMJ Case Reports; 2015, 2015:2–4 pp.10.1136/bcr-2015-210506Search in Google Scholar PubMed PubMed Central
8. Cutolo, M. Autoimmune polyendocrine syndromes. Autoimmun Rev 2014;13:85–9. https://doi.org/10.1016/j.autrev.2013.07.006.Search in Google Scholar PubMed
9. Kahaly, GJ. ‘Polyglandular autoimmune syndrome type II’. Presse Med 2012;41:e663–e670. https://doi.org/10.1016/j.lpm.2012.09.011.Search in Google Scholar PubMed
10. Bahceci, M, Tuzcu, A, Pasa, S, Ayyildiz, O, Tuzcu, S. Polyglandular autoimmune syndrome type III accompanied by common variable immunodeficiency. Gynecol Endocrinol 2004;19:47–50. https://doi.org/10.1080/09513590410001725279.Search in Google Scholar PubMed
11. Turkoglu, Z, Kavala, M, Kolcak, O, Zindanci, I, Can, B. Autoimmune polyglandular syndrome-3C in a child. Dermatol Online J 2010;16:8. https://doi.org/10.5070/d324p9n474.Search in Google Scholar
12. Zirilli, G, Santucci, S, Cuzzupè, C, Corica, D, Pitrolo, E, Salzano, G. Peculiarities of autoimmune polyglandular syndromes in children and adolescents. Acta Biomed 2017;88:271–5. https://doi.org/10.23750/abm.v88i3.5898.Search in Google Scholar PubMed PubMed Central
13. Kahaly, GJ, Frommer, L. Polyglandular autoimmune syndromes. J Endocrinol Invest 2018;41:91–8. https://doi.org/10.1007/s40618-017-0740-9.Search in Google Scholar
14. Valenzise, M, Aversa, T, Saccomanno, A, De Luca, F, Salzano, G. Epidemiological and clinical peculiarities of polyglandular syndrome type 3 in pediatric age’. Ital J Pediatr 2017;43:4–7. https://doi.org/10.1186/s13052-017-0386-4.Search in Google Scholar
15. Ruggeri, RM, Trimarchi, F, Giuffrida, G, Certo, R, Cama, E, Campennì, A. Autoimmune comorbidities in Hashimoto’s thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol 2017;176:133–41. https://doi.org/10.1530/eje-16-0737.Search in Google Scholar
16. Aversa, T, Corica, D, Zirilli, G, Pajno, GB, Salzano, G, De Luca, F. Phenotypic expression of autoimmunity in children with autoimmune thyroid disorders. Front Endocrinol 2019;10:1–7. https://doi.org/10.3389/fendo.2019.00476.Search in Google Scholar
17. Kahaly, GJ. Polyglandular autoimmune syndromes. Eur J Endocrinol 2009;161:11–20. https://doi.org/10.1530/eje-09-0044.Search in Google Scholar
18. Robles, DT, Fain, PR, Gottlieb, PA, Eisenbarth, GS. The genetics of autoimmune polyendocrine syndrome type II. Endocrinol Metab Clin N Am 2002;31:353–68. https://doi.org/10.1016/s0889-8529(01)00015-9.Search in Google Scholar
19. Maclaren, N. Addison’s disease 2001. J Clin Endocrinol Metab 2001;86:2909–22.10.1210/jcem.86.7.7636Search in Google Scholar
20. Quinkler, M. Addison’s disease. Med Klin Intensivmed Notfallmed 2012;107:454–9. https://doi.org/10.1007/s00063-012-0112-3.Search in Google Scholar
21. Schatz, DA, Winter, WE. Autoimmune polyglandular syndrome II: clinical syndrome and treatment. Endocrinol Metab Clin N Am 2002;31:339–52. https://doi.org/10.1016/s0889-8529(01)00012-3.Search in Google Scholar
22. Fichna, M, Fichna, P, Gryczyńska, M, Walkowiak, J, Zurawek, M, Sowiński, J. Screening for associated autoimmune disorders in Polish patients with Addison’s disease. Endocrine 2010;37:349–60. https://doi.org/10.1007/s12020-010-9312-x.Search in Google Scholar PubMed
23. Zelissen, PMJ, Bast, EJEG, Croughs, RJM. Associated autoimmunity in addison’s disease. J Autoimmun 1995;8:121–30. https://doi.org/10.1006/jaut.1995.0009.Search in Google Scholar PubMed
24. Neufeld, M, Maclaren, N, Blizzard, R. Autoimmune polyglandular syndromes. Pediatr Ann 1980;9:154–62. https://doi.org/10.3928/0090-4481-19800401-07.Search in Google Scholar
25. Dittmar, M, Kahaly, GJ. Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up. J Clin Endocrinol Metab 2003;88:2983–92. https://doi.org/10.1210/jc.2002-021845.Search in Google Scholar PubMed
26. Salardi, S, Volta, U, Zucchini, S, Fiorini, E, Maltoni, G, Vaira, B. Prevalence of celiac disease in children with type 1 diabetes mellitus increased in the mid-1990s: an 18-year longitudinal study based on anti-endomysial antibodies. J Pediatr Gastroenterol Nutr 2008;46:612–4. https://doi.org/10.1097/mpg.0b013e31815d697e.Search in Google Scholar
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Nephrogenic diabetes insipidus: a comprehensive overview
- Original Articles
- Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
- Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
- Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
- Evaluation of patients with phenylalanine metabolism disorder: a single center experience
- The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
- Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
- Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
- Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
- Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in FBP1
- Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
- Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
- Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
- Letter to the Editor
- Correspondence on “Obesity after the Covid-19 pandemic”
- Case Reports
- An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
- Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
- Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
- Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
Articles in the same Issue
- Frontmatter
- Review Article
- Nephrogenic diabetes insipidus: a comprehensive overview
- Original Articles
- Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
- Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
- Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
- Evaluation of patients with phenylalanine metabolism disorder: a single center experience
- The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
- Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
- Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
- Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
- Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in FBP1
- Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
- Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
- Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
- Letter to the Editor
- Correspondence on “Obesity after the Covid-19 pandemic”
- Case Reports
- An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
- Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
- Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
- Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
