HASHIMOTOS THYROIDITIS

HASHIMOTOS THYROIDITIS (CHRONIC LYMPHOCYTIC THYROIDITIS)

• It is an autoimmune disease with thyroid enlargement and progressive  destruction of thyroid gland leading to thyroid failure

• It was first described by Hasimoto in 1912 who described it as Struma lymphomotosa

• Age – occurs in middle aged women and can also occur in children

• Sex– More common in women than men with ratio of 10:1 to 20:1

• Familial association is present and is associated with HLA types DR3 and DR5. It is also found in association with other autoimmune disease

• Pathogenesis 

  • Caused by break down of self tolerance to thyroid autoantigen

  • Initiating event is possibly exposure of normally sequestered thyroid antigens or abnormalities of regulatory T cells 

  •  Increased susceptibility to Hashimotos thyroiditis is associated with polymorphism in immune regulation associated gene which are 

    • Cytotoxic T lymphocyte associated antigen – 4 (CTLA 4)

    • Protein tyrosine phosphatase – 22 (PTPN 22)

  • Both the genes code for regulation of T cell response

  • Immunological mechanism by which T cell cause thyroid destruction are 

    1. Activation of CD4+T cells which produce inflammatory cytokines like interferon γ in the thyroid gland causing recruitment and activation of macrophages, damaging the follicles

    2. CD8+ cytotoxic T cells destroy the thyroid follicular cells

    3. Antibody dependent cell mediated cytotoxiciy – Antithyroid antibodies are 

       • Anti thyroglobulin

       • Anti thyroid peroxidase (Thyroid microsomal antibodies)

       • TSH receptor autoantibodies

• Gross –

  • Thyroid is diffusely enlarged, firm and rubbery.

  • Cut section is fleshy nodular  pale, yellow tan to gray white 

•  Microscopy –

  • Extensive infiltration of parenchyma by mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells and well developed lymphoid follicles with germinal centres 

  • Thyroid follicles are atrophic with minimal colloid and are lined by hurthle cells which are metaplastic follicular epithelial cells having abundant eosinophilic cytoplasm which contains large number of mitochondria. They have round nuclei with prominent nucleoli. 

  • Hurthle cells are also called as Askanazy cells or oxyphil cells or oncocytes.

  • Hurthle cells may show nucleomegaly and anisokaryosis

  • Variants of Hashimotos thyroiditid is fibrous variant where the parenchyma is replacde by fibrous tissue and lymphoid infiltrate is less prominent

• Clinical features 

  • patient presents with painless symmetric and diffuse enlargement of thyroid gland

  • Most of the cases present with hypothyroidism and are middle aged women

  • Initially the patient is hyperthyroid due to disruption of thyroid follicles. During this phase T4 and T3 levels are elevated and TSH levels are diminished. Radioactive iodine uptake is decreased

  • During hypothyroidism, T4 and T3 levels fall accompanied by increased TSH

  • Patients having hypothyroidism are at increased risk of developing other autoimmune diseases like Type 1 diabetes, autoimmune adrenalitis, SLE, Myasthenia gravis

  • There is  an increased risk of development of extranodal marginal Zone B cell lymphoma and papillary carcinoma.