Very Interesting Study On Celiac And An Increased Risk Of Thyroid Cancer.

[frenchiemama]

Increased Risk of Papillary Thyroid Cancer in Celiac Disease

Laura Kent · Russell McBride · Robert McConnell · Alfred I. Neugut · Govind Bhagat · Peter H. R. Green

Received: 20 December 2005 / Accepted: 30 January 2006

C Springer Science+Business Media, Inc. 2006

Abstract Patients with celiac disease have an increased rate

of malignancies that are not limited to lymphomas. Thyroid

carcinoma has not previously been associated with celiac

disease. However, among a cohort of patients with celiac disease,

we identified an increased risk of papillary carcinoma

of the thyroid, standard morbidity ratio of 22.52 (95% confi-

dence interval 14.90–34.04; P < .001), compared to United

States national surveillance data. These patients were on a

gluten-free diet. Only 1 had Hashimoto’s thyroiditis, suggesting

that mechanisms apart from autoimmune thyroiditis

contribute to the increased risk of carcinoma of the thyroid

in celiac disease.

Introduction

Compared to the general population, patients with celiac

disease carry an increased burden of disease [1]. In addition

to autoimmune diseases [2] and endocrine disorders [3], patients

diagnosed with celiac disease have an increased risk of

a variety of malignancies that include both T-cell and B-cell

non-Hodgkin lymphoma, squamous carcinoma of the esophagus

and oropharynx, and small intestinal adenocarcinoma

[4–6]. In this report, we document a significantly increased

risk of papillary carcinoma of the thyroid in patients with

celiac disease.

Methods

We have maintained a database of patients diagnosed with

celiac disease who were seen in our Celiac Disease Center

since 1981. Data, including age at diagnosis, mode of

presentation, adherence to the gluten-free diet, and other diagnoses,

was prospectively entered into the database that

was anonymized to protect privacy. Among these patients

we identified 606, seen between July 1981 and April 2004,

who had biopsy-proven celiac disease.

The prevalence of papillary thyroid cancer in our database

was compared to data in the Surveillance, Epidemiology

and End Point Results (SEER) program of the National

Cancer Institute, Washington, D.C. [7]. Information

was accessed using Surveillance Research Program,

National Cancer Institute SEER∗Stat software(available:

www.seer.cancer.gov/seerstat) version 6.1.

Patient-years at riskwere calculated from the date of diagnosis

of celiac disease to either the date of diagnosis of cancer

or the date of the most recent follow-up visit, whichever

came first. We calculated the standardized morbidity ratio

(SMR), ratio of observed to expected and 95% confidence

intervals (CI), assuming that the observed number of cancers

had a Poisson distribution. Histopathology of thyroid cancer

was reviewed. The study was approved by the Institutional

Review Board of Columbia University.

Results

The database consisted of 606 patients; 68% were female

and the age at diagnosis of celiac disease was 41.5 ± 17.6 years. The prevalence of thyroid disease was 18.4%.

The classical diarrhea-predominant presentation of celiac

disease was noted in 43%. Three of these patients had papillary

thyroid cancer, whereas only 0.133 patients were expected,

resulting in a SMR of 22.52 (95% CI 14.90–34.04;

P < .001; Table 1). The prevalence for papillary thyroid cancer

was 494 per 100,000 compared to 22 per 100,000 of the

general population.

Of the patients with papillary thyroid cancer (Table 2), 2

were female and 1 male; the age at diagnosis of cancer was

44.3 years (range, 38–48 years), and mean duration since

diagnosis of celiac disease 7.7 years (range, 1–19.4 years).

Each had originally presented with diarrhea-predominant,

symptomatic celiac disease and responded to a gluten-free

diet. Adherence to the diet was strict as confirmed by an examination

of the dietary history by an experienced dietician

and negative celiac serologies. None of the patients had a

family history of thyroid cancer or a history of exposure to

radiation. Each patient presented with a thyroid nodule or

mass and was euthyroid, although one had positive thyroid

antibodies.

Two patients underwent total thyroidectomy and one

hemithyroidectomy. One of the patients had a follicular vari-

ant of papillary thyroid carcinoma, 2 patients had multifocal

and bilateral tumors, and 2 patients had lymph node involvement.

Hashimoto’s thyroiditis (as defined histologically because

of the presence of diffuse lymphocytic and plasma cell

infiltration with formation of lymphoid follicles, damage to

the follicular basement membrane, and Hurthle cell change

of the thyroid follicular epithelium) was identified in the resected

nonmalignant thyroid tissue in only 1 patient, who

had the positive thyroid antibodies.

Discussion

We observed a significantly increased risk of papillary thyroid

cancer in our cohort of patients with celiac disease compared

to United States national SEER data. This occurred

despite adherence to a gluten-free diet that is considered

protective against the development of malignancies [4]. One

of the patients was on the diet for only 1 year.

Thyroid disease, especially Hashimoto’s thyroiditis, is

common in patients with celiac disease [3]. Papillary thyroid

cancer occurs frequently in the setting of Hashimoto’s

thyroiditis [8, 9]. Because clinically significant papillary thyroid

cancer is observed in fewer patients with Hashimoto’s

thyroiditis than those who harbor precursor lesions [9],

it is likely that additional mutagenic events or immune

mechanisms might play important roles in papillary thyroid

cancer development. Because only 1 of our patients

had Hashimoto’s thyroiditis, additional mechanisms apart

from autoimmune thyroiditis may be important for the development

of papillary thyroid cancer in patients with celiac

disease. Such mechanisms could include chronic genotoxic

stress owing to chronic inflammation mediated by the lymphocytic

infiltrates and/or alternatively an as-yet uncharacterized

immune deregulation could lead to ineffective tumor

surveillance and indirectly lead to an increased incidence of

malignancies [10].

Thyroid cancer has not previously been reported as an

associated malignancy in series of adult patients with celiac

disease [5, 6, 11–15]. However, there were thyroid cancers

among a European series of children with celiac disease and

malignancies [16]; Freeman [17] has reported a thyroid lymphoma

in a patient with celiac disease. Our patients were

seen in a specialist referral setting that may have biased the

results. In addition, we are not aware of any regional factor

that could have influenced the increased occurrence of thyroid

cancer in these patients. However, this study should alert

clinicians to be aware of an increased risk of papillary thyroid

cancer in patients with celiac disease. Examination of

the thyroid should be performed as part of the regular physical

examination, and thyroid nodules should be evaluated by

ultrasonography and biopsy, to exclude thyroid cancer.

[georgie]

Scary stuff. All the more reason for me to keep taking my Iodine. I also have Pernicious Anaemia ( low B12) and that is autoimmune too, and also carries an extra risk of stomach cancer. It appears that having an autoimmune disease is bad news ....

[frenchiemama]

It appears that having an autoimmune disease is bad news ....

Too true, my friend. Too true. I actually have another one of these, showing that being a celiac carries an average 2x risk for ANY type of malignancy. Good reason for all of us to be careful with smoking, drinking, environmental exposure and eat a healthful diet.

[whereitscat]

Crazy. I had thyroid cancer 10 years ago, at age 21. Now I'm exploring celiac as a cause for IBS and constant headaches, and I just googled this on a whim. Makes me wonder if everything that's been wrong with me since I was young was related to celiac. I'm not diagnosed, but all the pieces are starting to fit together.