A study of fine needle aspiration cytology findings with thyroid function test, anti-thyroid antibody, and clinical pathological parameters in cases of chronic lymphocytic thyroiditis

Introduction

Thyroid disorders are one of the most widespread endocrine gland disorders in India. The Incidence of hypothyroidism in India is 30–60/1, 00,000 populations per year with an incidence rate of 1– 4%.1 The incidence rate of hypothyroidism in women of the reproductive age group is 2–4%.2 Hakaru Hashimoto described lymphocytic thyroiditis in 1912 for the first time. It is synonymous with Hashimoto thyroiditis and autoimmune thyroiditis. It is an autoimmune disease that affects women more often than men and is associated with hypothyroidism, euthyroidism or not so often with hyperthyroidism. However, most cases show symptoms of hypothyroidism. Autoimmune thyroiditis is the most common type of thyroiditis and the second most common benign thyroid lesion following colloid goitre.3, 4 This condition is most prevalent among the Asian population.5 It has been observed that iodine supplementation in iodine-deficient regions increases the incidence of lymphocytic infiltration of the thyroid three-fold, with a 40% rise in the incidence of antithyroid antibodies in serum over 0.5 to 5 years.6 The clinical presentation of autoimmune thyroiditis can range from diffuse to nodular swelling without symptoms.1 Characteristic cytological features include Hurtle cell changes, an increased number of reactive lymphoid and plasma cells, and the infiltration of lymphocytes into thyroid follicular cells.7 The most commonly detected autoantibody in the serum is Anti Thyroid Peroxidase Antibody (Anti TPO Ab); however, these may not be present in some cases. Subclinical hypothyroidism can be challenging to diagnose due to a lack of obvious symptoms. The presence of thyroid anti-TPO-Ab in serum is high in most of these patients. We used a predefined set of criteria for grading cytological features on FNAC smears, similar to the method used by Bhatia et al.7 The main aim is to correlate lymphocyte density with clinical, radiological, and biochemical parameters. The goal was to evaluate the sensitivity and specificity of FNAC, thyroid hormone assay, and Anti-TPO antibody levels preoperatively in patients with thyroid swellings and to determine the incidence of chronic lymphocytic thyroiditis by grading the cytological features of thyroid FNAC according to lymphocyte infiltration and comparing them with TFT and anti-TPO ab levels.

Aims and Objectives

Materials and Methods

This study is a retrospective study conducted in the Department of Pathology of ESIC Hospital in Delhi over the course of 2 years (from January 2020 to December 2021). The method used in this study was Fine Needle Aspiration Cytology (FNAC) of the thyroid gland using a non-aspiration/aspiration technique with a 23-gauge needle inserted into a 10 ml syringe. In cases of significant swelling, multiple-point aspirations were carried out. The samples were then air-dried, stained with May-Grunwald-Giemsa (MGG) and evaluated by a single pathologist who used Hamberger's criteria8 to judge the adequacy of the smears. i.e. at least six clusters of follicular cells on each of two slides prepared from separate aspirations. In cases where the initial sample was unsatisfactory, a repeat aspiration was attempted, but no more than three aspirations were attempted on each patient. The qualitative criteria used for cytological diagnosis included the presence of lymphocytes and plasma cells infiltrating the thyroid follicles, an increased number of lymphocytes in the background, and the presence of Hurthle cell change, multinucleated giant cells, epithelioid cell clusters, and anisonucleosis in the aspirate. The smears were then evaluated and graded quantitatively based on the criteria established by Bhatia et al.7 Simultaneously, Thyroid function tests (TFT) and Anti-TPO antibody levels were estimated using an automated hormone analyser. These results were then correlated with the patient's clinical presentation, TFT results, and anti-TPO antibody levels

Results

Patients included in this study were in age 11-70 years (Mean) with a male: female ratio of 1:3. The Highest no of patients was seen in the age group of 21 to 30 with the majority of patients being females 33(%). (Table 1) shows the Age and sex distribution of Autoimmune thyroiditis. Female preponderance has been observed in this study. Duration of thyroid swelling varied from patient to patient. In this study, the majority of patients (68.8%) reported experiencing midline neck swelling for a duration of 1-3 years. The shortest reported duration was eight months, while three patients had swelling for less than three years. The most commonly reported symptoms among patients were a pain in the swelling and rapid growth, both at a rate of (40.6%), followed by discomfort while swallowing (25%). Clinically, 16 patients were found to have a multi-nodular goitre, and 14 cases had solitary thyroid nodules. Through examination, it was determined that eight patients were euthyroid, seven were hyperthyroid, and 28 were hypothyroid. Table 2 illustrates the cytological grading of Hashimoto's thyroiditis, with five (32.5%) patients being classified as grade 1 due to mild lymphocytic infiltration of the gland (Figure 1). Additionally, eight patients (41.25%) were classified as grade 2, characterized by moderate lymphocytic infiltration with evidence of follicular destruction, Hurthle cell change, and giant cells (Figure 2, Figure 3). Lastly, 30 (26.24%) patients were classified as grade III, characterized by dense lymphocytic infiltrates with germinal centres and very few remaining follicular cells (Figure 4). The ultrasonography findings of patients with autoimmune thyroiditis show diffuse enlargement of the thyroid gland seen in 26 cases, multinodular goitre was seen in eight cases, a solitary nodule was seen in seven cases, and two cases show normal study. Twenty cases show a significant increase in high TSH levels, while anti-TPO antibody increased in 15 cases of grade 3 autoimmune thyroiditis. In contrast, five patients did not show any increase in TSH and anti-TPO antibodies.

Figure 1

Grade 2 Lymphocytic thyroiditis with Hurthle cell 400X

Figure 2

Grade 1 Lymphocytic thyroiditis 400X

Figure 3

Giant cell and, granuloma 100X

Figure 4

Grade 3 Lymphocytic thyroiditis 100X

Discussion

The thyroid is a vital endocrine gland that produces three hormones: triiodothyronine (T3) and thyroxine (T4) which are thyroid hormones, and calcitonin which is a peptide hormone. These hormones play a crucial role in regulating the metabolic rate, protein synthesis, growth, and development in children. They also play a vital role in normal reproduction and pregnancy. Autoimmune thyroiditis is a common cause of hypothyroidism. If left undiagnosed and untreated, it can lead to various complications such as abnormal sexual development, menstrual irregularities, infertility, sub-fertility in women of reproductive age group, and miscarriages and congenital malformations during pregnancy.9, 10 With an increasing prevalence of autoimmune thyroiditis, especially in women of childbearing age, the diagnosis of subclinical hypothyroidism can be challenging. The presence of elevated levels of thyroid autoantibodies in the blood is often seen in these cases, making cytological and serological evaluations essential for proper diagnosis and treatment. Autoimmune thyroiditis is characterized by the infiltration of T and B lymphocytes, which attack thyroid antigens and can lead to the destruction of the thyroid gland's follicular structure and replacement with fibrosis. Autoimmune thyroiditis is a common cause of hypothyroidism, especially in women of childbearing age. The disease's active phase can present as thyrotoxicosis, but it can also progress to subclinical or overt hypothyroidism. The exact cause of autoimmune thyroiditis is not fully understood, but it is thought to be influenced by factors such as iodine deficiency, medication, infection, smoking, and stress. Furthermore, autoimmune thyroiditis has an increased risk of developing into malignancy, particularly extra nodal marginal B-cell lymphoma and papillary carcinoma.11, 12 Autoimmune thyroiditis is a condition that requires ongoing monitoring, as it can have a significant impact on a patient's health. In our study, we evaluated 110 cases and found that the most common age group among patients was 21-30 years, which aligns with previous research by Ashwin et al.13 who also found a high incidence in the 20-40 age range. The typical presentation in our study was diffuse thyroid swelling 26 (60.47%) which bears resemblance with studies by Kartha S et al14 (66%) and Ashwin et al13 (50.81%). Grading of autoimmune thyroiditis was done per the criteria described in (Table 5). The majority of our cases belonged to Grade 3, 30 (69.77%). On analysing the TSH levels, we found 20 (28.57%) patients to be hypothyroid, which was in concordance with a study by Rathi et al,15 Ashwin et al,13 and P Agrawal et al16 who observed hypothyroidism in 56.1%, 50% and 50% cases, respectively. However, Bhatia et al7 reported hypothyroidism in 73.6% of patients. In our study, Anti-TPO Antibody was raised in 15 (21.43%), 3 (4.29%) and 1 (1.43%) cases of Grade 3, Grade 2 & Grade 1 categories of autoimmune thyroiditis, respectively. Similarly, the study conducted by Neelam Sood et al17 found elevated levels of Anti-TPO Antibody and TSH in a high percentage of cases across all grades of autoimmune thyroiditis, with 91.67%, 94.12% and 96.16% of patients in Grade 1, Grade 2 and Grade 3 respectively showing elevated levels.

Conclusion

Hashimoto’s thyroiditis is an autoimmune disorder that affects females more frequently than males and is typically found in individuals in their 20s and 30s. The most common clinical feature is hypothyroidism, which may be the initial presentation. The results of fine-needle aspiration cytology (FNAC) are often associated with abnormal biochemical findings in higher grades of Hashimoto's thyroiditis. The preliminary stages of the disease, characterized by diffuse thyroiditis (Grade 1), can occur before overt thyroid failure and is a strong predictor of the autoimmune process, even when the disorder is not suspected clinically. Grade 3 lymphocytic infiltration statistically correlates with thyroid peroxidase (TPO) and thyroid-stimulating hormone (TSH) levels. The study also found that anti-TPO and TSH levels, along with ultrasonographic findings of diffuse thyroid enlargement, are significant indicators of the disease. However, the presence of prominent Hurthle cell changes, giant cells, and granulomas did not statistically correlate with anti-TPO and TSH levels. A combination of cytological grading of Hashimoto's thyroiditis, ultrasonography, and biochemical levels can help detect subclinical hypothyroidism and guide treatment.

Source of Funding

None.

Conflict of Interest

None.