Probable impact of environmental radiation on thyroid swellings in areas of Eastern Hyderabad and Nalgonda

Thyroid swellings are prevalent in 4 to 7% of the Indian population and are commonly present in females. Thyroid swelling has been attributed to various causes, such as ingestion of goitrogens and low iodine in the diet in benign, radiation exposure, and genetic in malignancies. Eastern Hyderabad and Nalgonda have a high fluoride content in the ground water, which can potentially disrupt thyroid functioning. Moreover, the region also harbors high uranium content and environmental radiation; hence, a retrospective analysis of the FNAC and histopathology of the thyroid swellings was done to evaluate the paradigm. A retrospective analysis of the patient’s records from February 1, 2022, to January 31, 2023, was conducted considering all the patients who presented with thyroid swelling. The variables taken into consideration were age, gender, and FNAC findings. A correlation was also made with the histopathology of the specimen of operated patients. A total of 88 medical records of the patients were evaluated, and it was determined that there was a preponderance of females with a ratio of 8.77:1. Majority of the swellings were Benign labeled as Bethesda category 2 (n = 61) followed by category 3 (n = 11). To be considered are the cases of malignancies falling into category 6, which comprise 7.95% (n = 7). The majority of the patients were seen between the ages of 31 to 40 (n = 28), followed by 41 to 50 (n = 25). On comparing with the histopathological reports, two cases of category 5 were found to be having papillary thyroid carcinoma and another with follicular thyroid carcinoma making the number of proven malignancies to be 10.22% (n = 9). Other histopathological findings correlated with the results of FNAC. Through this pilot study, we conclude that most thyroid swellings were benign, but there is a higher incidence of thyroid malignancies (10.22%), significantly higher than the country average of 2 to 4%. The higher number of malignant cases can be attributed to many factors, including high fluoride content and environmental radiation. Further studies need to be conducted, taking each element individually.


Background
Thyroid malignancy occurs in 5 to 15% of thyroid nodules [1].The prevalence of thyroid malignancy, or thyroid cancer, varies depending on several factors such as age, gender, and geographic location [1,2].
According to the American Cancer Society's most recent estimates for thyroid cancer in the USA, for 2023, there are about 43,720 new cases of thyroid cancer (12,540 in men and 31,180 in women) and about 2120 deaths from thyroid cancer (970 in men and 1150 in women) [3].Ultrasound diagnosis of thyroid nodules has greatly increased their detection rate.Their malignancy risk is estimated at 7 and 15% in data from specialized centers used for guideline recommendations [4].
Ultrasonographic findings associated with malignant thyroid nodules include various characteristics.Malignant nodules often appear as completely solid or prominently solid on ultrasound imaging [5].Microcalcifications within a nodule are also considered suspicious features for malignancy [5,6].Irregular or micro-lobulated margins, marked hypoechogenicity compared with the strap muscles, and increased intranodular vascularity on Doppler imaging are additional ultrasound findings associated with malignant nodules.In contrast, malignant nodules may exhibit a taller than wide orientation, while benign nodules are typically wider than tall [5].Other suspicious sonographic criteria include marked hypoechogenicity, irregular margins, and abnormal lymph nodes.Eggshell calcifications surrounding the nodule are more commonly associated with benign nodules [6].
Clinical findings associated with malignant thyroid nodules can also provide important insights.Certain age groups and female gender have been associated with a higher risk of thyroid malignancy [7].Malignant nodules may be asymptomatic or present with symptoms such as pain or tenderness [7].The size and location of the nodules can raise suspicion for malignancy, with larger nodules and those located in specific regions of the thyroid gland being more concerning [8].Abnormal thyroid function tests, such as elevated thyroid-stimulating hormone (TSH) levels, have also been associated with malignancy [9].Additionally, the presence of enlarged lymph nodes in the neck, particularly those with abnormal sonographic features, may indicate the spread of malignancy [10,11].
The incidence of thyroid malignancy in the Indian population is not well-established, as there is limited data available on the prevalence and incidence of thyroid cancer in India.
The higher incidence of thyroid malignancies in Eastern Hyderabad and Nalgonda can be attributed to the region's high levels of environmental radiation.Radiation exposure is a well-established risk factor for the development of thyroid malignancy [13], and Eastern Hyderabad and Nalgonda, a district in the Indian state of Telangana, has been identified as an area with high levels of environmental radiation [14][15][16].The region is known for its large deposits of uranium, and past mining and milling activities have resulted in the release of radioactive materials into the surrounding environment [17].

Methods
A retrospective analysis was conducted on patient records between February 1, 2022, and January 31, 2023, including individuals with thyroid swelling.Due approval was taken from the concerned head of the department and competent authority to review the patient's records.The study analyzed various variables such as age, gender, and fine-needle aspiration cytology (FNAC) findings.The Bethesda classification system was used to categorize FNAC findings into six categories: nondiagnostic, benign, atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), follicular neoplasm/suspicious for follicular neoplasm (SFN), suspicious for malignancy, and malignant.Additionally, the study compared FNAC findings with the histopathology results of operated patients.

Results
Evaluating 88 medical records (data summarized in thyroid.xlsxsubmitted as Supplementary material) found that most patients were female, with a ratio of 8.77:1 (Fig. 1).Most of the swellings were determined to be benign and categorized as Bethesda 2 (n = 61) or Bethesda 3 (n = 11), while malignancies fell under the Bethesda 6 category and accounted for 7.95% (n = 7) of cases (Fig. 2).The highest cases were observed in patients aged 31 to 40 (n = 28) and those aged 41 to 50 (n = 25) (Fig. 3).Compared with the histopathological reports, two cases of category 5 were found to have papillary thyroid carcinoma and another with follicular thyroid carcinoma, making the number of proven malignancies 10.22% (n = 9) (Fig. 4).Other histopathological findings correlated with the results of FNAC.

Discussion
The increased occurrence of thyroid malignancies in Eastern Hyderabad and Nalgonda (a district in the Indian state of Telangana) can be attributed to the region's elevated levels of environmental radiation.As supported by studies, environmental radiation has long been recognized as a significant risk factor for the development of thyroid malignancies [13].Specifically, Eastern Hyderabad and Nalgonda have been identified as areas with notable environmental radiation levels, with several studies indicating this [14][15][16].This region is renowned for its abundant uranium deposits, and previous mining and milling activities have led to the release of radioactive substances into the surrounding environment [17].
Several studies have documented elevated levels of radiation exposure among residents of Eastern Hyderabad and Nalgonda and surrounding areas, including higher levels of naturally occurring radioactive materials such as radium and uranium in soil and groundwater [14][15][16].
Ionizing radiation can cause thyroid malignancies through several mechanisms, including direct DNA damage, indirect DNA damage, and altering gene expression, most commonly RET/PTC rearrangements increasing cell proliferation [18].Studies have demonstrated that radiation exposure can induce the formation of RET/ PTC rearrangements in thyroid cells [19].The risk of RET/PTC rearrangements increases with higher radiation doses delivered to the thyroid gland, with a higher susceptibility observed during childhood and decreasing with older age at exposure [18].The latency period between radiation exposure and the onset of thyroid cancer with RET/PTC rearrangements typically ranges from 5 to 10 years [18].
While RET/PTC rearrangements can also occur in sporadic cases of thyroid cancer, their prevalence is higher in radiation-associated thyroid cancer compared to sporadic cases [20].These findings underscore the impact of radiation-induced genetic alterations in the pathogenesis of thyroid cancer and highlight the significance of understanding the role of environmental radiation in disease development.
Genetic causes associated with thyroid malignancy are a mutation linked to RET proto-oncogene and association with multiple endocrine neoplasia 2 syndrome or a family history of medullary carcinoma of the thyroid [21].
Studies conducted in the region of Hyderabad and surrounding areas dealing with the cytological and histopathological correlation and others documenting the incidence in their health care center have reported the range of thyroid malignancies in the range of 10 to 14% which is significantly more than the national average of 3 to 4% [22][23][24][25].
Other risk factors, age, gender, and exposure to certain chemicals or substances, do not significantly affect the disease process.

Conclusion
This pilot study has led us to a significant findingwhile most thyroid swellings were benign, there was a notably higher incidence of thyroid malignancies (10.22%).This percentage is substantially higher than the country's average range of 2 to 4%, which is a cause for concern.We suspect this high incidence of malignancies could be attributed to various factors, with environmental radiation being a significant contributor.It is essential to conduct further studies that explore and investigate each factor individually to understand the underlying causes better.The implications of these findings are significant, and they call for immediate attention to this pressing issue.

Fig. 3 Fig. 4
Fig. 3 Age group distribution of FNAC as per Bethesda