The Frequency of Autoimmune Polyendocrinopathy Type 3b in Children with Type 1 Diabetes Mellitus

Abstract

Aim: Autoimmune polyendocrinopathy syndrome type 3 (APS3) is defined as the presence of autoimmune thyroid disease along with another autoimmune disorder other than Addison’s disease. If an autoimmune gastrointestinal disease is a component of the syndrome, it is defined as APS3b. In this study, we aimed to determine the frequency of APS3b in patients diagnosed with type 1 diabetes (T1D) in childhood. Material and Methods: A patient group of 446 children (232 males) with T1D whose follow-ups were conducted between 01.06.2013 and 31.08.2019 was included in the study. Hashimoto’s thyroiditis (HT) was defined with positive anti-TPO and/or anti-Tg test results whereas autoimmune enteropathy was defined with histologic findings which consisted with celiac disease (CD) in small bowel biopsy following a positive anti tissue transglutaminase IgA. Results: In total, 61 (13.7%) patients had HT and 34 (7.6%) patients had CD. While 87 (19.5%) of the patients had HT or CD, the occurrence of both HT and CD (APS3b) in the same patient was observed in only 4 patients (3 females) (0.9%). Patients with APS3b had low median age of diagnosis compared with patients with HT or CD alone, and patients with none of these two diseases, but the difference is not statistically significant (p=0.087). Conclusion: While HT or CD has been detected in approximately one-fifth of children with T1D, APS3b is rarely observed in this patient group.

Keywords

• Celiac disease
• Autoimmune polyendocrinopathy type 3b
• Autoimmune thyroid disease,
• Type 1 diabetes

Tip 1 Diabetes Mellitus Tanılı Çocuklarda Otoimmün Poliendokrinopati Tip 3b Sıklığı

Abstract

Amaç: Tip 3 otoimmün poliendokrinopati sendromu (OPS), Addison hastalığı olmaksızın otoimmün tiroid hastalığı ile diğer bir otoimmün hastalık birlikteliği olarak tanımlanmaktadır. Hastada otoimmün bir gastrointestinal hastalık olursa klinik tablo tip 3b OPS olarak tanımlanır. Bu incelemede çocukluk çağında tip 1 diyabet (T1D) tanısı almış hastalarda tip 3b OPS sıklığı araştırılması amaçlandı. Gereç ve Yöntemler: Çalışmaya 01.06.2013-31.08.2019 tarihleri arasında takibi yapılmış 232’si erkek 446 T1D’li çocuk çalışmaya alındı. Hashimoto tiroiditi (HT), pozitif anti TPO ve/veya anti-Tg pozitifliği ile otoimmün enteropati ise anti-doku transglutaminaz Ig A pozitifliğini takiben yapılmış ince bağırsak biyopsisinde çölyak hastalığı (ÇH) ile uyumlu histoloji varlığı ile tanımlandı. Bulgular: Hastaların 61’inde (%13,7) HT ve 34’ünde (%7,6) ÇH tespit edildi. Hastaların 87’sinde (%19,5) HT veya ÇH varken, aynı hastada hem HT hem de ÇH varlığı (tip 3b OPS) sadece 3’ü kız 4 hastada (%0,9) tespit edildi. Tip 3b OPS’li hastaların T1D tanı yaşı sadece HT veya sadece ÇH olanlar ve her iki hastalığı olmayanlar ile karşılaştırıldığında daha düşük olmakla birlikte istatistiksel bir farksaptanmadı (p=0,087). Sonuç: Çocukluk çağında tanı almış T1D’li çocukların yaklaşık beşte birinde HT veya ÇH tespit edilirken tip 3b OPS sıklığının oldukça nadir olduğu tespit edilmiştir.

Keywords

• Çölyak hastalığı
• Otoimmün tiroidit
• Tip 1 diyabet
• Tip 3b Otoimmün Poliendokrinopati Sendromu

References

1. 1. Kakleas K, Soldatou A, Karachaliou F, Karavanaki K. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmunity reviews. 2015;14(9):781-97.
2. 2. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocrine reviews. 2002;23(3):327-64.
3. 3. Brown RS. Autoimmune thyroiditis in childhood. J Clin Res Pediatr Endocrinol. 2013;5 Suppl 1:45-9.
4. 4. Ediger TR, Hill ID. Celiac disease. Pediatr Rev. 2014;35(10):409-15; quiz 16.
5. 5. Kahaly GJ, Frommer L. Polyglandular autoimmune syndromes. J Endocrinol Invest. 2018;41(1):91-8.
6. 6. Ben-Skowronek I, Michalczyk A, Piekarski R, Wysocka-Lukasik B, Banecka B. Type III Polyglandular Autoimmune Syndromes in children with type 1 diabetes mellitus. Annals of agricultural and environmental medicine : AAEM. 2013;20(1):140-6.
7. 7. Karaguzel G, Simsek S, Deger O, Okten A. Screening of diabetes, thyroid, and celiac diseases-related autoantibodies in a sample of Turkish children with type 1 diabetes and their siblings. Diabetes research and clinical practice. 2008;80(2):238-43.
8. 8. Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatric diabetes. 2018;19 Suppl 27:7-19.

9. 9. Neyzi O, Bundak R, Gokcay G, Gunoz H, Furman A, Darendeliler F, et al. Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol. 2015;7(4):280-93.
10. 10. Prina Cerai LM, Weber G, Meschi F, Mora S, Bognetti E, Siragusa V, et al. Prevalence of thyroid autoantibodies and thyroid autoimmune disease in diabetic children and adolescents. Diabetes care. 1994;17(7):782-3.
11. 11. Kordonouri O, Klinghammer A, Lang EB, Gruters-Kieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes care. 2002;25(8):1346-50.
12. 12. Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, Petrou V, et al. Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM). Hormone research. 2009;71(4):201-6.
13. 13. Lorini R, Gastaldi R, Traggiai C, Perucchin PP. Hashimoto's Thyroiditis. Pediatr Endocrinol Rev. 2003;1 Suppl 2:205-11; discussion 11.
14. 14. Shun CB, Donaghue KC, Phelan H, Twigg SM, Craig ME. Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis. Diabetic medicine : a journal of the British Diabetic Association. 2014;31(2):126-35.
15. 15. Mahmud FH, Elbarbary NS, Frohlich-Reiterer E, Holl RW, Kordonouri O, Knip M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Other complications and associated conditions in children and adolescents with type 1 diabetes. Pediatric diabetes. 2018;19 Suppl 27:275-86.
16. 16. Valenzise M, Aversa T, Saccomanno A, De Luca F, Salzano G. Epidemiological and clinical peculiarities of polyglandular syndrome type 3 in pediatric age. Italian journal of pediatrics. 2017;43(1):69.
17. 17. Larizza D, Calcaterra V, De Giacomo C, De Silvestri A, Asti M, Badulli C, et al. Celiac disease in children with autoimmune thyroid disease. J Pediatr. 2001;139(5):738-40.
18. 18. Sari S, Yesilkaya E, Egritas O, Bideci A, Dalgic B. Prevalence of celiac disease in Turkish children with autoimmune thyroiditis. Digestive diseases and sciences. 2009;54(4):830-2.
19. 19. Oderda G, Rapa A, Zavallone A, Strigini L, Bona G. Thyroid autoimmunity in childhood celiac disease. Journal of pediatric gastroenterology and nutrition. 2002;35(5):704-5.
20. 20. Meloni A, Mandas C, Jores RD, Congia M. Prevalence of autoimmune thyroiditis in children with celiac disease and effect of gluten withdrawal. J Pediatr. 2009;155(1):51-5, 5 e1.
21. 21. van der Pals M, Ivarsson A, Norstrom F, Hogberg L, Svensson J, Carlsson A. Prevalence of thyroid autoimmunity in children with celiac disease compared to healthy 12-year olds. Autoimmune diseases. 2014;2014:417356.
22. 22. Marwaha RK, Garg MK, Tandon N, Kanwar R, Narang A, Sastry A, et al. Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity. Indian J Med Res. 2013;137(1):82-6.
23. 23. Pocecco M, Ventura A. Coeliac disease and insulin-dependent diabetes mellitus: a causal association? Acta Paediatr. 1995;84(12):1432-3.
24. 24. Ide A, Eisenbarth GS. Genetic susceptibility in type 1 diabetes and its associated autoimmune disorders. Reviews in endocrine & metabolic disorders. 2003;4(3):243-53.
25. 25. von Herrath MG, Fujinami RS, Whitton JL. Microorganisms and autoimmunity: making the barren field fertile? Nature reviews Microbiology. 2003;1(2):151-7.
26. 26. Ventura A, Neri E, Ughi C, Leopaldi A, Citta A, Not T. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr. 2000;137(2):263-5.