Understanding Hashimoto’s and Graves’ Disease: Two Sides of the Thyroid Disorder Spectrum

Hashimoto’s Thyroiditis (HT) was first discovered and reported by Professor Hashimoto of Kyushu University, Japan, in 1912, which led to the naming of the condition.

Hashimoto’s Thyroiditis and Graves’ disease (GD) both fall under autoimmune thyroid diseases (AITD) and share similar pathogenic mechanisms, including thyroid lymphocytic inflammation and the presence of positive serum thyroid autoantibodies. The pathological process of Hashimoto’s Thyroiditis primarily involves immune cells and antibodies, leading to the destruction of thyroid cells.

The main antibodies associated with Hashimoto’s Thyroiditis are thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Approximately 95% of patients with HT have elevated TPOAb, and 60% have elevated TgAb [1]. As the disease progresses, thyroid function tests typically indicate elevated thyroid-stimulating hormone (TSH) levels and reduced levels of T3 and T4.

In patients with HT, the immune system continuously attacks thyroid cells, ultimately leading to thyroid damage and hypothyroidism (underactive thyroid). Clinically, this condition is managed with thyroid hormone replacement therapy, primarily using levothyroxine, to improve thyroid function and alleviate related symptoms of hypothyroidism [2].

Relationship between Hashimoto’s Thyroiditis and Graves’ disease:

Hashimoto’s Thyroiditis patients primarily exhibit symptoms of hypothyroidism, but hyperthyroidism symptoms may also occur. Apart from some patients who experience hyperthyroidism due to the dosage of thyroid hormone replacement therapy, another reason could be the coexistence of Graves’ disease.

When patients with HT also have positive thyroid receptor antibodies (TRAb), it indicates the presence of Graves’ disease as well.

The case study published in 2019 [2] documented a patient who initially presented with typical symptoms of hypothyroidism. The patient had positive TPOAb and TgAb, high TSH levels, and low T3 and T4 levels. However, after using thyroid hormone replacement therapy for two and a half months, hyperthyroidism symptoms appeared. Upon examination, it was found that TSH was below the normal range. Even after stopping the thyroid replacement medication for one month, TSH remained low, and T3 and T4 levels were higher than normal. At this point, not only were TPOAb and TgAb positive, but TRAb (thyroid receptor antibodies) were also positive, indicating the coexistence of Graves’ disease.

Other cases of patients diagnosed with HT developing hyperthyroidism have also been reported [3] [4] [5], but many of these patients with hyperthyroidism in Hashimoto Thyroiditis’ disease have positive TRAb antibodies. Therefore, a more accurate diagnosis for these patients may be Hashimoto’s thyroiditis progressing to Graves’ disease, leading to hyperthyroidism.

Although TPOAb and TgAb are characteristic antibodies of Hashimoto’s, they are also found in up to 70% of patients with Graves’ disease alone. Thus, relying solely on the presence of TPOAb and TgAb positivity makes it difficult to diagnose Hashimoto’s hyperthyroidism. In Hashimoto’s patients, TRAb positivity is also observed in 10% to 20% of cases, so the presence of TRAb antibodies cannot rule out Hashimoto’s disease [2].

It is important to note that in autoimmune thyroid diseases (AITD), Hashimoto’s and Graves’ may represent two aspects of the same disease spectrum. The recognized pathogenic mechanism of AITD involves a combination of susceptible genes and environmental factors. Both forms of AITD initially present with immune system imbalances, leading to inflammation in the body and the presence of positive autoantibodies in diagnostic tests. The subsequent health problems involve thyroid function impairment (hypothyroidism or hyperthyroidism) due to inflammation-mediated damage to different thyroid cells. When TPOAb, TgAb, TRAb, and other AITD autoantibodies are present, whether hyperthyroidism or hypothyroidism predominates may depend on the severity of damage to specific thyroid cells.

Summary

Hashimoto’s Thyroiditis (HT) and Graves’ disease (GD) are both types of autoimmune thyroid diseases characterized by the immune system attacking the thyroid gland. While HT leads to hypothyroidism (underactive thyroid), GD causes hyperthyroidism (overactive thyroid).

In Hashimoto’s Thyroiditis, the immune cells and antibodies target the thyroid cells, causing inflammation and damage to the thyroid gland. As a result, the thyroid’s ability to produce hormones is impaired, leading to hypothyroidism.

Two primary antibodies associated with Hashimoto’s Thyroiditis are thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb).

Some Hashimoto’s Thyroiditis patients may also experience symptoms of hyperthyroidism. This can occur due to the coexistence of Graves’ disease, another autoimmune thyroid disorder.

It’s essential to recognize that Hashimoto’s Thyroiditis and Graves’ disease may represent two aspects of the same autoimmune disease spectrum, with different thyroid function outcomes depending on the severity of cell damage caused by immune responses and autoantibodies.