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ORIGINAL ARTICLE
Year : 2016  |  Volume : 20  |  Issue : 1  |  Page : 97-100

Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact


Department of Endocrinology, BYL Nair Charitable Hospital and Topiwala National Medical College, Mumbai, Maharashtra, India

Date of Web Publication21-Dec-2015

Correspondence Address:
Bharat Rakeshkumar Sharma
Department of Endocrinology, Room No. 419, 4th Floor, College Building, Topiwala National Medical College and BYL Nair Charitable Hospital, AR Nair Road, Mumbai Central, Mumbai, Maharashtra - 400 008
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2230-8210.172241

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   Abstract 

Introduction: The prevalence of autoimmune thyroid disease (AITD) is 10–12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD) with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD) in this cohort helps reduce medication doses. Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA). Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase). Those with a positive titer (but < 10 times the upper limit of normal underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. Results: Of a total of 280 (182 females and 98 males) patients with AITD screened, 24 (8.6%) turned out to be positive for CA. Of 24 (8.6%), 15 (8.24%) females and 9 (9.18%) males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD.

Keywords: Autoimmunity, celiac disease, thyroid disease


How to cite this article:
Sharma BR, Joshi AS, Varthakavi PK, Chadha MD, Bhagwat NM, Pawal PS. Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact. Indian J Endocr Metab 2016;20:97-100

How to cite this URL:
Sharma BR, Joshi AS, Varthakavi PK, Chadha MD, Bhagwat NM, Pawal PS. Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact. Indian J Endocr Metab [serial online] 2016 [cited 2019 Jul 16];20:97-100. Available from: http://www.ijem.in/text.asp?2016/20/1/97/172241


   Introduction Top


The prevalence of autoimmune thyroid disease (AITD) worldwide in the general population is 10–12%.[1] Thyroid antibodies are present in 8–27% of the general population.[2] Its reported prevalence in India is 18–24%. Association of other autoimmune diseases with AITD as part of polyglandular autoimmune syndromes is well known. The prevalence of celiac disease (CD) in general population is only 1%, even though it has increased fourfold in the last three decades.[3]

The prevalence of celiac autoimmunity (CA) in the setting of AITD is 2–5%[4] with a prevalence of 4.1% in adults [4] and 7.8% in children.[5] Also, the largest longitudinal study to date of the condition showed that adults with CD had 4.4 times the relative risk of hypothyroidism and 2.9 times the risk of hyperthyroidism compared with the general population. In children, the rates were higher still at 6 times and 4.8 times the risk, respectively.[6] The co-existence of these two conditions is clinically significant with far-reaching implications in the management of thyroid disease. CD not only affects the absorption of several essential nutrients but also that of thyroxine used in the treatment of hypothyroidism. The time honored management of CD with institution of gluten-free diet (GFD) tends to prevent progression of histological changes in the intestine and may as well reverse them, thereby improving absorption parameters. A growing amount of research suggests that when people with CD and AITD adopt a GFD, not only do their celiac related antibody levels improve but also their thyroid antibody levels decrease.[7]

In view of the close association of the two conditions and the possible influence of GFD on the disease course of both, we undertook a study to determine the prevalence of CA in patients with AITD. To our knowledge, this is the first study of its kind in India.

Aims

The aim of our study was to screen patients with AITD for the presence of CA.


   Materials and Methods Top


The study was conducted at a large tertiary care center hospital in accordance with the code of ethics of World Medical Association (Declaration of Helsinki).

After obtaining written informed consent, a total of 280 consecutive patients with AITD(hypothyroid/hyperthyroid) attending the Out-patient Department of the hospital were recruited. The baseline characteristics of the patients (age, sex, history, anthropometry, goiter, and general physical examination) were noted down for future reference by a single examiner. Hypothyroidism was defined as a TSH value above 5.5 µ IU/ml by chemiluminometry (CLIA) with values between 5.5 and 10 µ IU/ml categorized as subclinical hypothyroidism and those over10 as overt hypothyroidism. Hyperthyroidism was defined as a TSH below 0.4 µ IU/ml with categorization into subclinical toxicosis and overt toxicosis based on T4, T3 estimation by CLIA. AITD was confirmed by measuring anti-thyroid peroxidise (anti-TPO) antibody levels in patients with thyroid dysfunction by CLIA. Levels above 60 U/L were taken as positive.

Exclusion criteria

Patients with thyrotoxicosis secondary to solitary thyroid nodule, thyroiditis and multinodular goiter, and all patients with negative TPO antibody status were excluded from the study. Patients with critical illnesses were also excluded from the study.

The above patients then underwent screening for CA through estimation of Immunoglobulin A tissue transglutaminase (IgA tTG) antibody levels. This was done using Bio-Rad enzyme-linked immunosorbent assay system. Those patients with IgA tTG levels above 15 U/L were considered positive for CA.

In accordance with the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines for the diagnosis of CD, unless the IgA tTG levels were more than 10 times the upper limit of normal, consenting patients underwent gastrointestinal endoscopy and duodenal biopsy for confirmation of CD. The diagnosis of CD was made pathologically using Marsh staging[Appendix 1]. Following confirmation of CD histologically, patients were advised regarding initiation of GFD by a registered dietitian.




   Results Top


Of a total of 280 (182 females and 98 males) patients with AITD screened, 24 (8 .6%) turned out to be positive for CA. Fifteen (8.24%) females and nine (9.18%) males were positive for CA. Of 24 (33 .33%), 8 patients had titers more than 10 times the upper limit of normal and so were directly initiated on GFD. Due to certain limitations, only 3 of the other 16 patients could undergo gastrointestinal endoscopy and duodenal biopsy. Of these three, only one patient had unequivocal changes of CD(Marsh stage three), while the other two had some degree of duodenitis (Marsh stage one). None of our patients had been screened for CA despite being diagnosed with AITD previously. Eighty percent of patients on retrospective probing agreed to be having some symptoms suggestive of CD, most notably gastritis (60%), abdominal pains (50%), and occasional loose motions (30%). The dose of thyroxine was 1.82 µg/kg in CA positive group and 1.79 µg/kg in CA negative group, the difference being not significant ( P = 0.72). Also, the average weight was 62.15 and 64.22 kg in the CA positive and negative groups, respectively, which again was not statistically significant ( P = 0.52). Fifteen of 24 (62 %) patients with CA had thyroid stimulating hormone levels in the therapeutic range as compared to 201 of 256 (78 %) patients without CA( P = 0.08). Statistical analysis was carried out using Statistical Package for Social Sciences (Internationial Business Machines (IBM)). Z-test was applied, as required, for comparing the means of the two groups (CA positive and CA negative).


   Discussion Top


Among autoimmune disorders, increased prevalence of CD has been found in patients with AITD, type 1 diabetes mellitus, autoimmune liver diseases, and inflammatory bowel disease. Conversely, CD patients themselves are prone to a number of other autoimmune disorders.

It has been hypothesized that the exposure to gluten in patients with CD triggers off autoimmunity against other tissues in the body. In an elaborate study by Ventura et al., it was observed that the prevalence of autoimmune disorders in CD is related to the duration of exposure to gluten. With progressively increasing age at diagnosis, the likelihood of the patient having concomitant autoimmune disorders was higher in this study.[8]

The association of CD with AITD is especially important as management of the former also affects that of the later as explained earlier. In addition to the gluten exposure hypothesis described above, CD and AITD also share common genetic predisposition. Human leukocyte antigen DQ2 and DQ8 are over-represented in CD and Graves' disease and to some extent in Hashimoto's thyroiditis.[9] Also, both CD and AITD are reported to be associated with the gene encoding cytotoxic T lymphocyte-associated antigen 4.[10],[11]

The prevalence of CA in AITD was found to be 8.6% in our study population. Our figures are comparable to some of the other studies done around the world. Collin et al., while screening 83 Finnish patients with AITD, found a CD prevalence of 4.8%.[12] Sategna-Guidetti et al. found 3.3% prevalence of CD in their 152 patients cohort of AITD using IgA anti-endomysial antibodies. Only one patient presented with gastrointestinal complaints.[13] Valentino et al. found 3.3% prevalence of CD in their cohort too.[14] Patients in the Valentino et al. study improved on a GFD with amelioration of hypothyroidism and thyroxine dose reduction. These studies confirm that the frequency of subclinical CD is increased in patients with AITD. IgA class antibody tests are suitable for screening.

There is also a group of patients referred to as “latent” CD, who have the requisite antibodies, but no mucosal abnormality to begin with. These patients may go on to develop overt CD as age progresses with progressive exposure to gluten.[15] In this context, the ESPGHAN has laid down guidelines for the management of CD. Those with antibody levels 10 times the upper limit of the assay used do not need a duodenal biopsy to confirm the diagnosis; while others do.

Limitations

Due to high attrition rates, it was not possible to obtain confirmatory tissue diagnosis in all CA positive patients.

Future prospects

Nutrient absorption (Vit B12, folate) and hemoglobin levels in AITD patients with and without CD, when compared, would be able to further establish the effects of CD on the same. With institution of GFD, both nutrient and thyroid medication absorptions should improve. Also, larger studies looking at differences in biopsy-confirmed CD cases to study impact of CA on AITD would be of interest.


   Conclusions Top


The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for the presence of CD. Though our population did not show any difference in the doses of thyroxine needed as well as the weight and thyronormalcy, further large-scale studies of a similar nature are needed as the literature is divided about the impact of CA in AITD.

Financial support and sponsorship

Department Development Fund, BYL Nair Charitable Hospital and Topiwala National Medical College.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
VanderpumpMP. The epidemiology of thyroid disease. Br Med Bull 2011;99:39-51.  Back to cited text no. 1
    
2.
Salvatore D, Davies TF, Schlumberger MJ, Hay ID, Larsen PR. Thyroid physiology and diagnostic evaluation of patients with thyroid disease. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Williams Textbook of Endocrinology. 12th ed. Philadelphia: Elsevier Saunders; 2011. p.355. [Table 11].14.  Back to cited text no. 2
    
3.
Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ. The spectrum of celiac disease: Epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol 2010;7:204-13.  Back to cited text no. 3
    
4.
Ch'ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res 2007;5:184-92.  Back to cited text no. 4
    
5.
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;139:738-40.  Back to cited text no. 5
    
6.
Elfström P, Montgomery SM, Kämpe O, Ekbom A, Ludvigsson JF. Risk of thyroid disease in individuals with celiac disease. J Clin Endocrinol Metab 2008;93:3915-21.  Back to cited text no. 6
    
7.
Ventura A, Neri E, Ughi C, Leopaldi A, Città A, Not T. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr 2000;137:263-5.  Back to cited text no. 7
    
8.
Ventura A, Magazzù G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology 1999;117:297-303.  Back to cited text no. 8
    
9.
Yanagawa T, Mangklabruks A, Chang YB, Okamoto Y, Fisfalen ME, Curran PG, et al. Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to Graves' disease in a Caucasian population. J Clin Endocrinol Metab 1993;76:1569-74.  Back to cited text no. 9
    
10.
Hunt KA, McGovern DP, Kumar PJ, Ghosh S, Travis SP, Walters JR, et al. A common CTLA4 haplotype associated with coeliac disease. Eur J Hum Genet 2005;13:440-4.  Back to cited text no. 10
    
11.
Chistiakov DA, Turakulov RI. CTLA-4 and its role in autoimmune thyroid disease. J Mol Endocrinol 2003;31:21-36.  Back to cited text no. 11
    
12.
Collin P, Salmi J, Hällström O, Reunala T, Pasternack A. Autoimmune thyroid disorders and coeliac disease. Eur J Endocrinol 1994;130:137-40.  Back to cited text no. 12
    
13.
Sategna-Guidetti C, Bruno M, Mazza E, Carlino A, Predebon S, Tagliabue M, et al. Autoimmune thyroid diseases and coeliac disease. Eur J Gastroenterol Hepatol 1998;10:927-31.  Back to cited text no. 13
    
14.
Valentino R, Savastano S, Tommaselli AP, Dorato M, Scarpitta MT, Gigante M, et al. Prevalence of coeliac disease in patients with thyroid autoimmunity. Horm Res 1999;51:124-7.  Back to cited text no. 14
    
15.
Mäki M, Holm K, Koskimies S, Hällström O, Visakorpi JK. Normal small bowel biopsy followed by coeliac disease. Arch Dis Child 1990;65:1137-41.  Back to cited text no. 15
    




 

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