Silent thyroiditis pathophysiology

The exact pathogenesis of silent thyroiditis is not fully understood. It is thought that silent thyroiditis is the result of an autoimmune phenomenon. Activated matured T-cells (HLA-DR+CD3+), activated helper/inducer T-cells (HLA-DR+CD4+), activated suppressor, and cytotoxic T-cells (HLA-DR+CD8+) were higher in patients with silent thyroiditis as compared to the healthy controls. It indicates that the activation of T cells, especially helper/inducer T cells, might have an important role in the pathogenesis of silent thyroiditis. Silent thyroiditis is associated with the HLA-DR3 and DR5 genes. Lymphocytic infiltration of the thyroid gland, the absence of Hurthle cells and germinal centers on histological analysis are the microscopic histopathological findings suggestive of silent thyroiditis.

The control, synthesis, and release of the thyroid hormone is usually controlled by hypothalamus and pituitary gland.[1][2] Thyroid hormones (T3 and T4) regulates the basal metabolic rate and influences oxygen consumption by tissues. They are crucial for normal development of the brain and growth of the body. Secretion of thyroid hormones follows upper control mechanisms from the hypothalamus and the pituitary. Thyroid releasing hormone (TRH) acts on thyrotropes releasing cells in the pituitary causing them to release thyroid stimulating hormone (TSH). TSH acts on thyroid gland by binding to specific membrane receptors and activating an intracellular pathway involving cAMP that ends in the formation and secretion of thyroid hormones. Iodine is essential for the synthesis of thyroid hormones. Iodide is taken up through a special Na/I transporter found in the membrane of thyroid follicular cell. After the iodide uptake, it goes through a series of organic reactions ending in the formation of the two forms of thyroid hormones: T3 and T4. T3 and T4 remain stored in the thyroglobulin within thyroid follicles and are released in response to further stimulation by TSH to the thyroid follicles. While T3 is 3 to 5 times more potent than T4, it represents only one-fourth of the total hormone secretion. T3 is thought to be the biologically active form of the hormone. Most of the circulating T3 is due to peripheral conversion of T4 in the liver and peripheral tissues while only a small percentage is secreted directly from the thyroid gland itself. T3 and T4 act on nuclear receptors (DNA binding proteins) and cause the regulate the transcription of many proteins to regulate the metabolic rate of the body. The higher regulation of thyroxine secretion follows the negative feedback role, meaning that high levels of T3 and T4 will suppress TRH and TSH secretion and vice versa (Low levels of thyroxine will stimulate TRH and TSH secretion). This is useful in diagnosing the cause of hyperthyroidism. TSH will be low in primary hyperthyroidism where the gland is the source of the excess hormones. In secondary hyperthyroidism, TSH will be high as the pituitary or the hypothalamus are the sources of the disease.

• The exact pathogenesis of silent thyroiditis is not fully understood. It is thought that silent thyroiditis is the result of an autoimmune phenomenon. The following features are suggestive of an autoimmune pathogenesis of silent thyroiditis:^[3][4][5][6]
  • Lymphocytic infiltration of the thyroid gland
  • Presence of antithyroid antibodies
  • Association with HLA-DR3 and DR5
  • Presence of anti-DNA antibodies

• Activated matured T-cells (HLA-DR+CD3+), activated helper/inducer T-cells (HLA-DR+CD4+), activated suppressor, and cytotoxic T-cells (HLA-DR+CD8+) were higher in patients with silent thyroiditis as compared to the healthy controls. It indicates that the activation of T-cells, especially of helper/inducer T cells, might have an important role in the pathogenesis of silent thyroiditis.^[7]

Silent thyroiditis is associated with the following HLA genes:^[5]

• HLA-DR3
• HLA-DR5

The following conditions are associated with silent thyroiditis:^{[8][9][10][11]}

• SLE
• Lymphocytic hypophysitis
• Immune thrombocytopenic purpura (ITP)
• Cushing’s syndrome (post adrenalectomy and steroid therapy cessation)
• Hodgkin’s lymphoma (post-irradiation)

Gross pathology findings in silent thyroiditis include:^[12]

• Diffuse goiter
• Slightly enlarged thyroid gland

• Microscopic histopathological findings in silent thyroiditis include:^[3][13]
  • Diffuse lymphocytic infiltrate
  • Lack of Hurthle cells (Askanazy cells) and germinal centers
  • Lack of fibrosis

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