|Year : 2019 | Volume
| Issue : 2 | Page : 66-70
Clinical, biochemical, and cytomorphological profile of lymphocytic thyroiditis: A study from a medical college in the Kangra Valley, India
Manish Sharma1, Rashmi Kaul Raina1, Suman Singh1, Sujeet Raina2
1 Department of Pathology, Dr. RP Government Medical College, Kangra, Himachal Pradesh, India
2 Department of Medicine, Dr. RP Government Medical College, Kangra, Himachal Pradesh, India
|Date of Web Publication||15-Jul-2019|
Dr. Rashmi Kaul Raina
C-15, Type-V Quarters, Dr. RP Government Medical College Campus, Tanda, Kangra . 176 001, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Background: Lymphocytic thyroiditis has not been studied in the population of this sub-Himalayan region in North India.
Aims: The aim is to study the clinical, biochemical, and cytomorphological profile of lymphocytic thyroiditis.
Methodology: Patients diagnosed with lymphocytic thyroiditis on cytology between August 2017 and July 2018 were included for further evaluation. The demographic characters, clinical features, biochemical and radiology findings of the patients were analysed in this hospital based cross-sectional study.
Results: The clinical, biochemical, and cytomorphological profile of 52 patients were analyzed. The mean age was 37.2 ± 14.2 years. Female patients were 46 (88.4%). Grade II thyroiditis was seen in 42 (80.8%) cases followed by Grade I in 8 (15.4%) and Grade III in 2 (3.8%) cases. Thyroid-stimulating hormone level was normal in 18 (34.6%), increased in 16 (30.8%), and decreased in 18 (34.6%) cases. Antithyroid peroxidase was done in 37 patients and was raised in 35 (94.5%) cases.
Conclusion: In this study, cytological grades of thyroiditis correlate poorly with clinical, biochemical, and ultrasonography findings.
Keywords: Chronic autoimmune thyroiditis, Hashimoto's thyroiditis, sub-Himalayan region
|How to cite this article:|
Sharma M, Raina RK, Singh S, Raina S. Clinical, biochemical, and cytomorphological profile of lymphocytic thyroiditis: A study from a medical college in the Kangra Valley, India. Thyroid Res Pract 2019;16:66-70
|How to cite this URL:|
Sharma M, Raina RK, Singh S, Raina S. Clinical, biochemical, and cytomorphological profile of lymphocytic thyroiditis: A study from a medical college in the Kangra Valley, India. Thyroid Res Pract [serial online] 2019 [cited 2019 Oct 18];16:66-70. Available from: http://www.thetrp.net/text.asp?2019/16/2/66/262731
| Introduction|| |
Chronic lymphocytic thyroiditis is synonymous with autoimmune thyroiditis and includes Hashimoto's thyroiditis (goitrous thyroiditis) and nongoitrous atrophic thyroiditis. The disorder is most common in women, and the spectrum of clinical presentation ranges from asymptomatic, large goiter (diffuse or nodular) to an atrophic gland, euthyroidism, hypothyroidism, and rarely hyperthyroidism. The pathologic changes include marked lymphocytic infiltration of the thyroid with germinal center formation, atrophy of the thyroid follicles accompanied by oxyphil metaplasia, absence of colloid, and mild-to-moderate fibrosis. The presence of thyroid peroxidase (TPO) antibody is a feature of autoimmune thyroiditis. The hyperthyroid variant is closely related to Graves' disease on gross examination and microscopic appearance. Thyroid-stimulating hormone (TSH) receptor antibodies confirm the diagnosis of Graves' disease in such cases. The autoimmune process involves an underlying genetic predisposition and a trigger(s) that initiate the cascade of events. The identified triggers are infections, life stress, iodine intake, smoking, medications such as amiodarone and interferon, radiation, and environmental toxicants.
Fine-needle aspiration (FNA) is the method of choice for primary diagnosis of thyroid swellings. It is safe, reliable, and cost-effective in making the diagnosis as well as grading the lymphocytic thyroiditis. Population studies in India found a prevalence of juvenile autoimmune thyroiditis (the term included both Hashimoto's thyroiditis and focal lymphocytic thyroiditis) as 7.5% in a countrywide screening of goitrous healthy young girls of 10–18 years of age and 6.02% among schoolchildren of 6–18 years., In hospital-based studies, the prevalence of lymphocytic thyroiditis among patients with thyroid swelling subjected to FNA varied from 7.6% to 15.3%.,, Our study was carried out in a medical college located in the rural hilly setting of the Kangra Valley, India, a known belt of endemic goiter and iodine deficiency. A goiter prevalence of 55% was reported from the district of Kangra in Himachal Pradesh in 1956. In the postiodization phase, the goiter prevalence has remarkably decreased, but it is still persisting in the region. The prevalence of goiter was reduced to 12.1% in 1999 in this district. Despite years of salt iodization under the universal iodization program, the total goiter rate was found to be 19.8% in 2004. The aims and objectives of this study were to evaluate the cytomorphological spectrum of lymphocytic thyroiditis and its association with clinical and thyroid hormone values and ultrasound findings.
| Methodology|| |
The study was conducted in a tertiary care referral hospital of Kangra district in Himachal Pradesh, India. The hospital caters to the medical needs of the population residing in the physiographic region of Shivalik and lesser Himalayas and includes lower hills of Kangra, Hamirpur, Una, and Bilaspur and lower parts of Mandi and Chamba districts. The district Kangra in Himachal Pradesh is a known area of endemic iodine deficiency.
The study was conducted in two steps. In Step 1, all patients with goiter when they presented to the department of pathology and subjected to FNA cytology were recruited. This formed the sampling frame for identifying study participants for this study. This was followed by Step 2 of the study wherein all patients diagnosed with lymphocytic thyroiditis on cytology were included for further evaluation. Recruitment of cases was done using an open cohort design conducted from August 1, 2017, to July 31, 2018, for a period of 1 year. Slides were examined in the department of pathology by two experienced senior pathologists who are co-authors (RKR and SSC) of this study. Data of patients including demographic, clinical, biochemical, and radiology were entered as per the structured pro forma. Thyroid function tests (T3, T4, and TSH) and thyroid peroxidase antibody were done on serum samples by chemiluminescent immunoassay on IMMULITE 1000 system (Siemens Healthcare, Germany).
It was defined as lymphocytes and plasma cells infiltrating the thyroid follicles and increased number of lymphocytes in the background with or without lymphoid follicles, Hurthle cell change, multinucleated giant cells, epithelioid cell clusters, anisonucleosis, or interlobular fibrosis that is the presence of fibrous tissue or scattered fibroblasts in the aspirate.
Grading of lymphocytic thyroiditis into Grade I (mild), Grade II (moderate), and Grade III (severe) was done according to the criteria of Bhatia et al.
The thyroid function was assessed on TSH levels. The TPO was positive when the antibody level was ≥30 U/ml.
Data were analyzed in Microsoft Excel 2010. Qualitative data have been calculated in the form of frequency and percentage. Quantitative data have been presented as mean ± standard deviation.
The study was approved by the Institutional Ethics Committee.
| Results|| |
A total of 217 were referred for FNA of the thyroid gland during the study period. The cytological diagnosis of lymphocytic thyroiditis was made in 52 patients. The age of the patients ranged from 10 to 80 years, and the mean age was 37.2 ± 14.2 years. Female patients were 46 (88.4%). Goiter was the clinical presentation in all the patients. In addition, pain in the neck was associated features in 4 (7.7%) cases. Among patients with pain, two were hypothyroid and one each was euthyroid and hyperthyroid. Cervical lymphadenopathy was observed in two patients. On cytology of these, reactive hyperplasia was seen. Grade II thyroiditis [Figure 1]c was the most frequent cytomorphological finding and was seen in 42 (80.8%) of cases followed by Grade I [Figure 1]a and [Figure 1]b in 8 (15.4%) and Grade III [Figure 1]d in 2 (3.8%). [Table 1] shows the distribution of age, sex, and cytological grades of lymphocytic thyroiditis. TSH level was normal in 18 (34.6%), increased in 16 (30.8%), and decreased in 18 (34.6%) of cases. Anti-TPO was done in 37 patients and was positive in 35 (94.5%) cases. The relationship between the cytological grades and findings on ultrasound are shown in [Figure 2]. The relationship between thyroid hormone status, TPO antibody, and cytological grades of lymphocytic thyroiditis is shown in [Table 2]. The distribution of patients showing the relationship between TPO antibody and thyroid hormone status is shown in [Table 3].
|Figure 1: (a) Grade I thyroiditis showing an increased number of lymphocytes (Giemsa, ×200). (b) Grade I thyroiditis showing an increased number of lymphocytes (Giemsa, ×400). (c) Grade II thyroiditis is showing lymphocytic infiltration into follicle showing Hurthle cell changes (Giemsa, ×400). (d) Grade III thyroiditis showing florid lymphocytic infiltrations (Giemsa, ×200)|
Click here to view
|Table 1: Distribution of grade of lymphocytic thyroiditis with age and sex (n=52)|
Click here to view
|Table 2: Relation of cytological grade of lymphocytic thyroiditis, thyroid peroxidase, and thyroid-stimulating hormone status (n=37)|
Click here to view
|Table 3: Distribution of cases according to antithyroid peroxidase and thyroid hormone status (n=37)|
Click here to view
| Discussion|| |
India is passing through being iodine-deficient to iodine-sufficient state. Nearly 91% of households in the country have access to iodized salt with 71% consuming adequately iodized salt, and another 20% is consuming salt with some added iodine (<15 ppm). Iodine supplementation in the iodine-deficient areas increases the prevalence of lymphocytic infiltration of the thyroid by 3-fold. The prevalence of thyroid autoantibody positivity in such areas rises to over 40% within 5 years of initiating supplementation. Whether this transition is followed by a spurt in autoimmune thyroid disorders in India also is not known. The absence of robust preiodization prevalence data does not permit any conclusion. In a study from preiodization era, the prevalence of thyroid autoantibodies in individuals over 50 years of age in India were found to be 25.9% among females and 7.7% among males. In the postiodization period, TPO antibody was found positive in 13.3% among adult individuals (18–90 years) in a study done in Delhi and in 16.7% of adult individuals of urban coastal area of central Kerala in India., Moreover, when individuals with abnormal thyroid function were excluded, the prevalence of anti-TPO and anti-TG antibodies was 9.5% and 8.5%, respectively. The results of these preiodization and postiodization prevalence studies do not suggest a spurt in autoimmune thyroid disorders in India. Autoimmune thyroid disorders are an important cause of goiter in the postiodization phase in India.
The prevalence of lymphocytic thyroiditis among patients with thyroid swelling subjected to FNA was 23.9% (52/217) in our study. The prevalence varied from 7.6% to 15.3% in hospital-based studies from India.,, The prevalence was 7.5% in a population based countrywide screening of goitrous healthy young girls of 10-18 years of age. The higher prevalence in our study could be due to either immunogenic predisposition of this population or as a result of iodization in a known endemic region. Most of the patients were females (7.6:1). The reason for the disparity is due to female sex steroid hormones and X chromosome containing a number of sex- and immune-related genes., Most of the patients were in the 21–40-year (53.8%) age group. The finding is consistent with other Indian studies and is in contrast to western studies where it is mostly diagnosed in the 4th–6th decade. Autoimmune thyroid disease has an early onset in endemic goiter and iodine deficiency areas that are now iodine sufficient. Goiter was the presenting complaint in all the patients. The finding is consistent with other Indian studies. Goiter is a strong reason for seeking medical care in our population. In addition, pain in the neck was associated feature in 4 (7.7%) patients. Hashimoto's thyroiditis is generally painless, and painful presentation has been rarely reported. Cervical lymphadenopathy was present in two cases in our study. On cytology of lymph node, both the patients had reactive hyperplasia. Benign hyperplastic neck lymph nodes are common in chronic autoimmune thyroiditis. On ultrasonography, diffusely enlarged gland with hypoechoic echotexture was observed in 55.8% of patients. In the remaining patients, the gland was diffusely enlarged with heterogeneous echotexture, or multiple nodularities were observed. Normal to hypoechogenicity has been reported in studies from India.,, On ultrasound, the features of Hashimoto's thyroiditis are diffuse goiter with decreased echogenicity, heterogeneity, hypervascularity, and the presence of hypoechoic micronodules with echogenic rim. Thyroid enlargement with diffuse hypoechogenicity favors autoimmune thyroid disease. Low echogenicity is due to altered thyroid structure because of the disruption of follicles and diffuse lymphocytic infiltration. Cytology grades correlated poorly with ultrasound findings in this study. Anti-TPO was positive in 94.5% cases in this study. The results are consistent with other studies from India., A strong correlation between cytology and antibody was observed in our study. However, discrepancy between cytological and antibody has been well recognized in other studies.,, Most of the patients in our study belonged to cytology Grade II followed by Grade I. Variable results have been observed on cytological grading in the different studies as compared in [Table 4]. The cytological grades and biochemical results have also shown a poor correlation in these studies as is observed in [Table 4]. Thyroid hormone status based on TSH levels in this study revealed that 18 (34.6%) patients were either euthyroid or hyperthyroid. Hypothyroidism was observed in 16 (30.8%) patients in this study. Although hypothyroidism is the predominant clinical scenario in lymphocytic thyroiditis, cytomorphological features do not reflect a consistent hormonal status as is evident from different studies shown in [Table 4]. Earlier in the course of the disease, patients may exhibit signs, symptoms, and laboratory findings of hyperthyroidism or normal values. This is because the destruction of the thyroid gland cells may be intermittent. The clinical significance of euthyroid patients with cytological evidence of lymphocytic thyroiditis is not clear at present. Little is known about progression in adults with euthyroid status to hypothyroid state in HT. Progression from euthyroid to hypothyroid state has been suggested in children with HT.
| Conclusion|| |
It was observed that cytological grading into mild, moderate, and severe grades of thyroiditis correlates poorly with clinical, biochemical, and ultrasonographic findings. Serological evidence of autoimmunity by the presence of TPO antibody is strong in our patients and correlates well with cytology. Serology a noninvasive method is not inferior to cytomorphology in making a diagnosis of lymphocytic thyroiditis in our population.
The help of Mr. Sushant Sharma, Lecturer Statistics, Department of Community Medicine, Dr. R.P. Government Medical College, Kangra (Tanda), Himachal Pradesh, India, for statistical analysis is gratefully acknowledged.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Baloch ZW, Livolsi VA. Pathology and cytopathology. In: Braverman LE, Cooper DS, editors. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 10th
ed. Philadelphia: Lippincott Williams and Wilkins; 2013. p. 326-53.
Brent GA. Environmental exposures and autoimmune thyroid disease. Thyroid 2010;20:755-61.
Marwaha RK, Tandon N, Karak AK, Gupta N, Verma K, Kochupillai N, et al.
Hashimoto's thyroiditis: Countrywide screening of goitrous healthy young girls in postiodization phase in India. J Clin Endocrinol Metab 2000;85:3798-802.
Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N, et al.
Residual goitre in the postiodization phase: Iodine status, thiocyanate exposure and autoimmunity. Clin Endocrinol (Oxf) 2003;59:672-81.
Anila KR, Nayak N, Jayasree K. Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters. J Cytol 2016;33:145-9.
] [Full text]
Kumar N, Ray C, Jain S. Aspiration cytology of Hashimoto's thyroiditis in an endemic area. Cytopathology 2002;13:31-9.
Saraf SR, Gadgil NM, Yadav S, Kalgutkar AD. Importance of combined approach of investigations for detection of asymptomatic Hashimoto thyroiditis in early stage. J Lab Physicians 2018;10:294-8.
] [Full text]
Kapil U, Sohal KS, Sharma TD, Tandon M, Pathak P. Assessment of iodine deficiency disorders using the 30 cluster approach in district Kangra, Himachal Pradesh, India. J Trop Pediatr 2000;46:264-6.
Kapil U, Sharma TD, Singh P. Iodine status and goiter prevalence after 40 years of salt iodisation in the Kangra district, India. Indian J Pediatr 2007;74:135-7.
Bhatia A, Rajwanshi A, Dash RJ, Mittal BR, Saxena AK. Lymphocytic thyroiditis – Is cytological grading significant? A correlation of grades with clinical, biochemical, ultrasonographic and radionuclide parameters. Cytojournal 2007;4:10.
] [Full text]
UNICEF. Coverage Evaluation Survey 2009, All India Report. New Delhi: Ministry of Health and Family Welfare, Government of India; 2010. Available from: http://www.unicef.org/india/health.html
. [Last accessed on 2011 Jul 01].
Harach HR, Escalante DA, Onativia A, Lederer Outes J, Saravia Day E, Williams ED, et al.
Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis. Acta Endocrinol (Copenh) 1985;108:55-60.
Boukis MA, Koutras DA, Souvatzoglou A, Evangelopoulou A, Vrontakis M, Moulopoulos SD, et al.
Thyroid hormone and immunological studies in endemic goiter. J Clin Endocrinol Metab 1983;57:859-62.
Pang T, Yap SF, Ngan A, Bosco J. Prevalence of thyroid autoantibodies in an Asian population. Singapore Med J 1980;21:483-6.
Marwaha RK, Tandon N, Ganie MA, Kanwar R, Sastry A, Garg MK, et al.
Status of thyroid function in Indian adults: Two decades after universal salt iodization. J Assoc Physicians India 2012;60:32-6.
Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H, et al.
High prevalence of undetected thyroid disorders in an iodine sufficient adult South Indian population. J Indian Med Assoc 2009;107:72-7.
Agrawal NK. Thyroiditis. Indian Thyroid Guidelines 2011. J Assoc Physicians India 2011;59:46-50.
Mousa U, Cuneyd A, Alptekin G. Should neck pain in a patient with Hashimoto's thyroiditis be underestimated? A case and review of the literature. Indian J Endocrinol Metab 2012;16:444-6.
Brancato D, Citarrella R, Richiusa P, Amato MC, Vetro C, Galluzzo CG, et al.
Neck lymph nodes in chronic autoimmune thyroiditis: The sonographic pattern. Thyroid 2013;23:173-7.
Thomas T, Sreedharan S, Khadilkar UN, Deviprasad D, Kamath MP, Bhojwani KM, et al.
Clinical, biochemical and cytomorphologic study on Hashimoto's thyroiditis. Indian J Med Res 2014;140:729-35.
] [Full text]
Marwaha RK, Sankar R, Magdum M, Nijahvan VS, Khanna CM, Jaggi CB, et al.
Clinical, biochemical and cytomorphological observations in juvenile chronic lymphocytic thyroiditis. Indian Pediatr 1998;35:967-73.
Anderson L, Middleton WD, Teefey SA, Reeding CC, Langer JE, Desser T, et al
. Hashimoto thyroiditis. Part 2. Sonographic analysis of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis. AJR Am J Roentgenol 2010;195:216-22.
Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A, et al.
Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 1991;72:209-13.
Radetti G, Gottardi E, Bona G, Corrias A, Salardi S, Loche S, et al.
The natural history of euthyroid Hashimoto's thyroiditis in children. J Pediatr 2006;149:827-32.
Kudva R, Kishore M. Hashimoto's thyroiditis: A correlation of cytolomorphology with clinical, biochemical & radiological findings. Int J Sci Res 2015;4:1771-4.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]