Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism

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Abstract

Background: B12 (cobalamin) deficiency has been reported in hypothyroid patients with variable prevalence rates thus routine screening of hypothyroid patients was recommended by some and discouraged by others. We aimed to assess the prevalence of B12 deficiency among hypothyroid patients and to evaluate for pernicious anemia and celiac disease as etiologies.

Methods: A total 133 patients were included. Thyroid hormones and thyroid peroxidase (TPO) autoantibodies were measured. Serum B12 was measured and if deficient, intrinsic factor antibodies (IFAB) and tissue transglutaminase (tTG) antibodies were evaluated.

Results: Our study included 45 patients with overt hypothyroidism (OH), 48 patients with subclinical hypothyroidism (SCH), and 40 patients as controls. Mean age was 34.3 years and 82% were females. TPO antibodies were positive in 73.5% of OH and 51.1% of SCH patients. B12 deficiency was detected in 33.3%, 47.9%, and 37.5% of OH, SCH, and controls, respectively with no significant difference (P = .334). Borderline-to-low B12 level was more prevalent in the OH and the SCH groups compared to controls (68.9%, 85.4%, and 57.5%, respectively; P = .014). Among B12-deficient hypothyroid patients, 7.5% had positive IFAB and 13.3% had positive tTG antibodies. We did not find a significant association of TPO positivity and B12 deficiency (OR, 0.69; 95% CI 0.3-1.57; P = .147).

Conclusion: We did not find a higher prevalence of B12 deficiency among hypothyroid patients nor an association with TPO positivity. Borderline B12 levels were more prevalent among hypothyroid patients.

Keywords: Vitamin B12 deficiency; celiac disease; hypothyroidism; pernicious anemia; subclinical hypothyroidism.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


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KMEL References


References

  1.  
    1. Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med. 2007;232:1266-1274. - PubMed
  2.  
    1. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368:149-160. - PubMed
  3.  
    1. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89:693S-696S. - PubMed
  4.  
    1. Rothen JP, Walter PN, Tsakiris DA, Infanti L, Hersberger KE, Arnet I. Identification of patients with cobalamin deficiency crucially depends on the diagnostic strategy. Clin Lab. 2021;67:1229-1235. doi:10.7754/Clin.Lab.2020.200912 - DOI - PubMed
  5.  
    1. İspir E, Serdar MA, Ozgurtas T, et al.. Comparison of four automated serum vitamin B12 assays. Clin Chem Lab Med. 2015;53:1205-1213. - PubMed
  6.  
    1. Kulnigg-Dabsch S. Autoimmune gastritis. Wien Med Wochenschr. 2016;166:424-430. - PMC - PubMed
  7.  
    1. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390:1550-1562. - PMC - PubMed
  8.  
    1. Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99:923-931. - PubMed
  9.  
    1. Almandoz JP, Gharib H. Hypothyroidism: etiology, diagnosis, and management. Med Clin North Am. 2012;96:203-221. - PubMed
  10.  
    1. Collins AB, Pawlak R. Prevalence of vitamin B-12 deficiency among patients with thyroid dysfunction. Asia Pac J Clin Nutr. 2016;25:221-226. - PubMed
  11.  
    1. Das C, Sahana PK, Sengupta N, Giri D, Roy M, Mukhopadhyay P. Etiology of anemia in primary hypothyroid subjects in a tertiary care center in Eastern India. Indian J Endocrinol Metab. 2012;16:S361-S363. - PMC - PubMed
  12.  
    1. Ness-Abramof R, Nabriski DA, Braverman LE, et al.. Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease. Am J Med Sci. 2006;332:119-122. - PubMed
  13.  
    1. Jabbar A, Yawar A, Waseem S, et al.. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008;58:258-261. - PubMed
  14.  
    1. What is Celiac Disease? Celiac Disease Foundation. Accessed September 24, 2021. https://celiac.org/about-celiac-disease/what-is-celiac-disease/
  15.  
    1. Dahele A, Ghosh S. Vitamin B12 deficiency in untreated celiac disease. Am J Gastroenterol. 2001;96:745-750. - PubMed
  16.  
    1. Aktaş HŞ. Vitamin B12 and Vitamin D levels in patients with autoimmune hypothyroidism and their correlation with anti-thyroid peroxidase antibodies. Med Princ Pract. 2020;29:364-370. - PMC - PubMed
  17.  
    1. Mehmet E, Aybike K, Ganidagli S, Mustafa K. Characteristics of anemia in subclinical and overt hypothyroid patients. Endocr J. 2012;59:213-220. - PubMed
  18.  
    1. Lippi G, Montagnana M, Targher G, Salvagno GL, Guidi GC. Prevalence of folic acid and vitamin B12 deficiencies in patients with thyroid disorders. Am J Med Sci. 2008;336:50-52. - PubMed
  19.  
    1. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005;82:442-450. - PubMed
  20.  
    1. OpenEpiMenu. Accessed December 15, 2018. https://www.openepi.com/Menu/OE_Menu.htm
  21.  
    1. Aroda VR, Edelstein SL, Goldberg RB, et al.. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101:1754-1761. - PMC - PubMed
  22.  
    1. Cappellini MD, Motta I. Anemia in clinical practice-definition and classification: does hemoglobin change with aging? Semin Hematol. 2015;52:261-269. - PubMed
  23.  
    1. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia: diagnose and treat iron deficiency anemia. Am J Hematol. 2016;91:31-38. - PubMed
  24.  
    1. Pearce SH, Brabant G, Duntas LH, et al.. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013;2:215-228. - PMC - PubMed
  25.  
    1. Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid. 2007;17:1211-1223. - PubMed
  26.  
    1. McLeod DSA, Caturegli P, Cooper DS, Matos PG, Hutfless S. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA. 2014;311:1563. - PubMed
  27.  
    1. Collet TH, Bauer DC, Cappola AR, et al.. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis. J Clin Endocrinol Metab. 2014;99:3353-3362. - PMC - PubMed
  28.  
    1. Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab. 1990;71:661-669. - PubMed
  29.  
    1. Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017;376:2556-2565. - PubMed
  30.  
    1. Duyff RF, Van den Bosch J, Laman DM, van Loon BJP, Linssen WHJP. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry. 2000;68:750-755. - PMC - PubMed
  31.  
    1. Jaya Kumari S, Bantwal G, Devanath A, Aiyyar V, Patil M. Evaluation of serum vitamin B12 levels and its correlation with anti-thyroperoxidase antibody in patients with autoimmune thyroid disorders. Indian J Clin Biochem. 2015;30:217-220. - PMC - PubMed
  32.  
    1. Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166:496-513. - PubMed
  33.  
    1. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011;94:348S-358S. - PMC - PubMed
  34.  
    1. Al Zenki S, Alomirah H, Al Hooti S, et al.. Prevalence and determinants of anemia and iron deficiency in Kuwait. Int J Environ Res Public Health. 2015;12:9036-9045. - PMC - PubMed
  35.  
    1. Atak B, Aktas G, Duman TT. Association between thyroid hormone status and complete blood count parameters in anemic patients. Malays J Med Health Sci. 2021;17:101-104.
  36.  
    1. Husebye ES, Anderson MS, Kämpe O. Autoimmune polyendocrine syndromes. N Engl J Med. 2018;378:1132-1141. - PMC - PubMed
  37.  
    1. Wang YP, Lin HP, Chen HM, Kuo YS, Lang MJ, Sun A. Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels in patients with anti-thyroid autoantibodies. J Formos Med Assoc. 2014;113:155-160. - PubMed
  38.  
    1. Szczepanek-Parulska E, Hernik A, Ruchała M. Anemia in thyroid diseases. Pol Arch Intern Med. 2017;127:352-360. doi:10.20452/pamw.3985 - DOI - PubMed
  39.  
    1. M’Rabet-Bensalah K, Aubert CE, Coslovsky M, et al.. Thyroid dysfunction and anaemia in a large population-based study. Clin Endocrinol. 2016;84:627-631. - PubMed
  40.  
    1. Damon LE, Andreadis CB. Blood disorders. In: Papadakis Maxine A, McPhee Stephen J, eds. Current Medical Diagnosis and Treatment. 60th ed. McGraw Hill; 2021:519-520.
  41.  
    1. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129:2603-2611. - PubMed
  42.  
    1. Bailey RL, Carmel R, Green R, et al.. Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12. Am J Clin Nutr. 2011;94:552-561. - PMC - PubMed
  43.  
    1. Carmel R. Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing. Biochimie. 2013;95:1047-1055. - PubMed
  44.  
    1. García García B, Gimeno Orna JA, Aguillo Gutiérrez E, et al.. Prevalencia y factores predictivos de la presencia de anticuerpos anticélula parietal gástrica en la enfermedad tiroidea autoinmune. Endocrinol Nutr. 2010;57:49-53. - PubMed
  45.  
    1. Checchi S, Montanaro A, Ciuoli C, et al.. Prevalence of parietal cell antibodies in a large cohort of patients with autoimmune thyroiditis. Thyroid. 2010;20:1385-1389. - PubMed
  46.  
    1. Zubarik R, Ganguly E, Nathan M, Vecchio J. Celiac disease detection in hypothyroid patients requiring elevated thyroid supplementation: A prospective cohort study. Eur J Intern Med. 2015;26:825-829. - PubMed
  47.  
    1. Hadizadeh Riseh S, Abbasalizad Farhang M, Mobasseri M, Asghari Jafarabadi M. The relationship between thyroid hormones, antithyroid antibodies, anti-tissue transglutaminase and anti-gliadin antibodies in patients with Hashimoto’s thyroiditis. Acta Endocrinol. 2017;13:174-179. - PMC - PubMed
  48.  
    1. Marwaha RK, Garg MK, Tandon N, et al.. Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity. Indian J Med Res. 2013;137:82-86. - PMC - PubMed
  49.  
    1. Hopper AD, Hadjivassiliou M, Hurlstone DP, et al.. What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol. 2008;6:314-320. - PubMed