Journal of Endocrinological Investigation

, Volume 43, Issue 1, pp 81–86 | Cite as

Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease

  • V. CalcaterraEmail author
  • C. Montalbano
  • E. Miceli
  • O. Luinetti
  • R. Albertini
  • F. Vinci
  • C. Regalbuto
  • D. Larizza
Original Article



Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening.


We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves’ disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam.


PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed.


In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.


Anti-gastric parietal cell antibodies Autoimmune gastritis Screening Children Autoimmune thyroid disease 



The authors thank Dr. L. Kelly for English revision of the manuscript.


This research did not receive any funding from public, commercial, or non-profit agencies.

Compliance with ethical standards

Conflict of interest

The authors have no competing interests to declare.

Ethical approval

This study was approved by the San Matteo Institutional Review Board and conducted according to the Declaration of Helsinki.

Informed consent

All parents of the children and/or the patients gave their written informed consent authorizing the use of their medical records for research purposes.


  1. 1.
    Hunter I, Greene SA, MacDonald TM et al (2000) Prevalence and aetiology of hypothyroidism in the young. Arch Dis Child 83:207–210PubMedPubMedCentralGoogle Scholar
  2. 2.
    Tomer Y (2014) Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol 9:147–156PubMedPubMedCentralGoogle Scholar
  3. 3.
    Tomer Y (2010) Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid 20:715–725PubMedPubMedCentralGoogle Scholar
  4. 4.
    Cappa M, Bizzarri C, Crea F (2010) Autoimmune thyroid diseases in children. J Thyroid Res 2011:675703PubMedPubMedCentralGoogle Scholar
  5. 5.
    González-Amaro R, Marazuela M (2016) T regulatory (Treg) and T helper 17 (Th17) lymphocytes in thyroid autoimmunity. Endocrine 52:30–38PubMedGoogle Scholar
  6. 6.
    Santaguida MG, Gatto I, Mangino G, Virili C et al (2017) BREG cells in Hashimoto’s thyroiditis isolated or associated to further organ-specific autoimmune diseases. Clin Immunol 184:42–47PubMedGoogle Scholar
  7. 7.
    Ramos-Leví AM, Marazuela M (2016) Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms. Endocrinol Nutr 63:421–429PubMedGoogle Scholar
  8. 8.
    Minelli R, Gaiani F, Kayali S et al (2018) Thyroid and celiac disease in pediatric age: a literature review. Acta Biomed 89(9-S):11–16PubMedGoogle Scholar
  9. 9.
    Sahin Y, Evliyaoglu O, Erkan T et al (2018) The frequency of celiac disease in children with autoimmune thyroiditis. Acta Gastroenterol Belg 81:5–8PubMedGoogle Scholar
  10. 10.
    OrzanA Novac C, Mihu M et al (2016) Type 1 diabetes and thyroid autoimmunity in children. Maedica (Buchar) 11:308–312Google Scholar
  11. 11.
    Singh P, Seth A, Kumar P, Sajjan S (2017) Coexistence of celiac disease and type 1 diabetes mellitus in children. Indian J Med Res 145:28–32PubMedPubMedCentralGoogle Scholar
  12. 12.
    Kochummen E, Marwa A, Umpaichitra V et al (2018) Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes. J Pediatr Endocrinol Metab 31:879–885PubMedGoogle Scholar
  13. 13.
    Ferrari SM, Fallahi P, Ruffilli I et al (2019) The association of other autoimmune diseases in patients with Graves’ disease (with or without ophthalmopathy): review of the literature and report of a large series. Autoimmun Rev. CrossRefPubMedGoogle Scholar
  14. 14.
    Rodriguez-Castro KI, Franceschi M, Miraglia C et al (2018) Autoimmune diseases in autoimmune atrophic gastritis. Acta Biomed 89(8):100–103PubMedGoogle Scholar
  15. 15.
    Utiyama SRR, De Bem RS, Skare TL et al (2018) Anti-parietal cell antibodies in patients with autoimmune thyroid diseases. J Endocrinol Investig 41:523–529Google Scholar
  16. 16.
    Cellini M, Santaguida MG, Virili C et al (2017) Hashimoto’s thyroiditis and autoimmune gastritis. Front Endocrinol (Lausanne) 8:92Google Scholar
  17. 17.
    Besançon A, Michaud B, Beltrand J et al (2017) Revisiting autoimmune gastritis in children and adolescents with type 1 diabetes. Pediatr Diabetes 18:772–776PubMedGoogle Scholar
  18. 18.
    Saglietti C, Sciarra A, Abdelrahman K et al (2018) Autoimmune gastritis in the pediatric age: an underestimated condition report of two cases and review. Front Pediatr 6:123PubMedPubMedCentralGoogle Scholar
  19. 19.
    Li Y, Xia R, Zhang B, Li C (2018) Chronic atrophic gastritis: a review. J Environ Pathol Toxicol Oncol 37:241–259PubMedGoogle Scholar
  20. 20.
    Minalyan A, Benhammou JN, Artashesyan A et al (2017) Autoimmune atrophic gastritis: current perspectives. Clin Exp Gastroenterol 10:19–27PubMedPubMedCentralGoogle Scholar
  21. 21.
    Segni M, Borrelli O, Pucarelli I et al (2004) Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases. J Clin Endocrinol Metab 89:4944–4948PubMedGoogle Scholar
  22. 22.
    Dixon MF, Genta RM, Yardley JH, Correa P, The participants in the International workshop of the Histopathology of gastritis (1996) Classification and grading of gastritis. The updated Sydney-Houston system. Am J Surg Pathol 20:1161–1181PubMedGoogle Scholar
  23. 23.
    Stolte M, Meining A (2001) The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol 15:591–598PubMedGoogle Scholar
  24. 24.
    Whittingham S, Mackay IR (1985) Pernicious anemia and gastric atrophy. In: Rose NR, Mackay IR (eds) The autoimmune diseases. Academic Press, New York, pp 243–266Google Scholar
  25. 25.
    Jacobson DL, Gange SJ, Rose NR et al (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 84:223–243PubMedGoogle Scholar
  26. 26.
    Kahaly GJ (2009) Polyglandular autoimmune syndromes. Eur J Endocrinol 161:11–20PubMedGoogle Scholar
  27. 27.
    Betterle C, Dal Pra C, Mantero F et al (2002) Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 23:327–364PubMedGoogle Scholar
  28. 28.
    Antonelli A, Ferrari SM, Corrado A et al (2015) Autoimmune thyroid disorders. Autoimmun Rev 14:174–180PubMedGoogle Scholar
  29. 29.
    Toh BH, Chan J, Kyaw T et al (2012) Cutting edge issues in autoimmune gastritis. Clin Rev Allergy Immunol 42:269–278PubMedGoogle Scholar
  30. 30.
    Venerito M, Radünz M, Reschke K et al (2015) Autoimmune gastritis in autoimmune thyroid disease. Aliment Pharmacol Ther 41:686–693PubMedGoogle Scholar
  31. 31.
    Zhang Y, Weck MN, Schöttker B et al (2013) Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: evidence from a large population-based study in Germany. Cancer Epidemiol Biomark Prev 22:821–826Google Scholar
  32. 32.
    Kuitunen P, Mäenpää J, Krohn K et al (1971) Gastrointestinal findings in autoimmune thyroiditis and non-goitrous juvenile hypothyroidism in children. Scand J Gastroenterol 6:336–341PubMedGoogle Scholar
  33. 33.
    Pita Gutiérrez F, Crespo Marcos D, Iglesias Fernández C et al (2009) Autoimmune thyroid disease: autoimmune gastritis association’s possibility. An Pediatr (Barc) 71:240–243Google Scholar
  34. 34.
    Tozzoli R, Kodermaz G, Perosa AR et al (2010) Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five-year prospective study in patients with autoimmune thyroid diseases. Autoimmun Rev 10:80–83PubMedGoogle Scholar
  35. 35.
    Miceli E, Padula D, Lenti MV et al (2015) A laboratory score in the diagnosis of autoimmune atrophic gastritis: a prospective study. J Clin Gastroenterol 49:e1–e5PubMedGoogle Scholar
  36. 36.
    Miceli E, Lenti MV, Padula D et al (2012) Common features of patients with autoimmune atrophic gastritis. Clin Gastroenterol Hepatol 10:812–814PubMedGoogle Scholar
  37. 37.
    Gonçalves C, Oliveira ME, Palha AM et al (2014) Autoimmune gastritis presenting as iron deficiency anemia in childhood. World J Gastroenterol 20:15780–15786PubMedPubMedCentralGoogle Scholar
  38. 38.
    Marignani M, DelleFave G, Mecarocci S et al (1999) High prevalence of atrophic body gastritis in patients with unexplained microcytic and macrocytic anemia. Am J Gastroenterol 94:766–772PubMedGoogle Scholar
  39. 39.
    Sibilla R, Santaguida MG, Virili C et al (2008) Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated with autoimmune related disorders. Clin Endocrinol (Oxf) 68:640–645Google Scholar
  40. 40.
    Malik TH, Sayahan MY, Al Ahmed HA et al (2017) Gastric intestinal metaplasia: an intermediate precancerous lesion in the cascade of gastric carcinogenesis. J Coll Phys Surg Pak 27:166–172Google Scholar
  41. 41.
    Song JH, Kim SG, Jin EH et al (2017) Risk factors for gastric tumorigenesis in underlying gastric mucosal atrophy. Gut Liver 11:612–619PubMedPubMedCentralGoogle Scholar
  42. 42.
    Rugge M, Meggio A, Pravadelli C et al (2019) Gastritis staging in the endoscopic follow-up for the secondary prevention of gastric cancer: a 5-year prospective study of 1755 patients. Gut 68:11–17PubMedGoogle Scholar
  43. 43.
    Rugge M, Genta RM, Fassan M et al (2018) OLGA gastritis staging for the prediction of gastric cancer risk: a long-term follow-up study of 7436 patients. Am J Gastroenterol 113:1621–1628PubMedGoogle Scholar
  44. 44.
    Rotondi M, Coperchini F, Magri F, Chiovato L (2014) Serum-negative autoimmune thyroiditis: what’s in a name? J Endocrinol Investig 37:589–591Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • V. Calcaterra
    • 1
    • 2
    Email author
  • C. Montalbano
    • 1
    • 2
  • E. Miceli
    • 3
    • 4
  • O. Luinetti
    • 5
    • 6
  • R. Albertini
    • 7
  • F. Vinci
    • 1
    • 2
  • C. Regalbuto
    • 1
    • 2
  • D. Larizza
    • 1
    • 2
  1. 1.Pediatric and Adolescent Unit, Department of Internal MedicineUniversity of PaviaPaviaItaly
  2. 2.Pediatric Endocrinology Unit, Department of Maternal and Children’s HealthFondazione IRCCS Policlinico San MatteoPaviaItaly
  3. 3.First Department of Internal MedicineFondazione IRCCS Policlinico San MatteoPaviaItaly
  4. 4.University of PaviaPaviaItaly
  5. 5.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  6. 6.Pathology UnitFondazione IRCCS Policlinico San MatteoPaviaItaly
  7. 7.Laboratory of Clinical ChemistryFondazione IRCCS Policlinico San MatteoPaviaItaly

Personalised recommendations