Hashimoto’s thyroiditis (HT) is an autoimmune disorder where the immune system attacks the thyroid gland, which produces hormones for metabolism. Thyroid cancer involves the uncontrolled growth of cells, most commonly Papillary Thyroid Carcinoma (PTC). Research shows a significant co-occurrence between HT and PTC, suggesting a relationship between chronic autoimmune inflammation and malignancy.
Understanding Hashimoto’s Thyroiditis
Hashimoto’s thyroiditis (HT) is characterized by the gradual, immune-mediated destruction of the thyroid gland. It is defined by the infiltration of thyroid tissue by lymphocytes, which forms dense aggregates. This continuous immune attack leads to chronic inflammation and progressive fibrosis, replacing normal thyroid tissue with scar tissue.
The inflammation often impairs the thyroid’s ability to produce sufficient hormones, leading to hypothyroidism. HT is associated with autoantibodies in the blood, such as thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). The thyroid gland may become enlarged, called a goiter, due to inflammatory infiltration, though the gland may shrink in later stages.
The Direct Relationship Between Hashimoto’s and Thyroid Cancer
Hashimoto’s thyroiditis is frequently found alongside thyroid cancer, particularly Papillary Thyroid Carcinoma (PTC). Studies indicate that 11% to 36% of patients undergoing surgery for thyroid cancer are also found to have HT upon pathological examination. This suggests a clear association between the two conditions.
This relationship is understood as a correlation, not direct causation. However, the presence of HT has been identified as an independent risk factor for the development of PTC. One large analysis reported a relative risk of PTC among HT patients of about 1.40, indicating a heightened likelihood of cancer compared to the general population.
When PTC is found alongside Hashimoto’s, the cancer often displays less aggressive features compared to PTC in a non-inflamed gland. Patients with concurrent HT tend to have a better prognosis, showing lower rates of lymph node metastasis and extrathyroidal extension. This suggests the intense immune response of Hashimoto’s may help contain the cancer.
Biological Mechanism of Increased Risk
The biological mechanisms connecting HT to increased cancer risk center on chronic inflammation and hormonal stimulation. The persistent immune attack creates a pro-inflammatory microenvironment within the thyroid. This constant cycle of cellular damage, repair, and high cell turnover increases the probability of genetic mutations accumulating in follicular cells, potentially initiating cancerous transformation.
The activation of signaling pathways, such as the NF-κB pathway, is implicated in this process, as it is involved in inflammation and cell survival. The chronic inflammatory state leads to the production of reactive oxygen species (ROS), molecules that directly damage DNA and contribute to oncogenic changes. These cellular changes, under prolonged inflammation, create a fertile ground for malignancy.
The role of Thyroid Stimulating Hormone (TSH) is another factor. When HT causes hypothyroidism, TSH levels rise to stimulate the failing thyroid gland. Elevated TSH acts as a growth factor for thyroid cells, and this chronic stimulation can promote the proliferation of pre-cancerous cells. Maintaining TSH within a target range through hormone replacement therapy can mitigate this growth stimulus.
Specific molecular alterations are common in PTCs that coexist with HT, including a lower rate of the aggressive BRAF V600E gene mutation. Genetic rearrangements, such as the RET/PTC rearrangement, are thought to play a significant role in PTC development, potentially influenced by the immune environment. The interaction between inflammation, TSH stimulation, and these molecular pathways collectively drives the association between the two diseases.
Monitoring and Surveillance for Patients with Hashimoto’s
Given the established association, patients with HT require careful monitoring for signs of thyroid cancer. Surveillance includes regular physical examination of the neck to check for new lumps or changes. This is supplemented by periodic thyroid ultrasound, the preferred imaging tool for evaluating the gland’s structure.
Ultrasound screening is important for detecting thyroid nodules, which are common in HT patients. The presence of HT can make ultrasound evaluation challenging because the inflamed thyroid tissue often has a heterogeneous or irregular appearance. If a nodule is found, its characteristics, such as size, shape, and suspicious features like microcalcifications, determine the need for further investigation.
Nodules with concerning features may require a Fine Needle Aspiration (FNA) biopsy to check for cancer cells. Patients with HT and low-risk PTC may be candidates for active surveillance, involving close monitoring with repeated ultrasounds instead of immediate surgery. Communication with an endocrinologist is necessary to establish a personalized surveillance schedule based on risk factors and ultrasound findings.