Reference Work Entry

Encyclopedia of Molecular Mechanisms of Disease

pp 775-776

Hashimoto's Thyroiditis

  • Seda SancakAffiliated withMarmara University Medical SchoolIII. Medical Department, University of Leipzig
  • , Ralf PaschkeAffiliated withIII. Medical Department, University of Leipzig


Hashimoto's disease; Goitrous autoimmune thyroiditis [1]

Definition and Characteristics

Positive thyroid peroxidase antibodies (TPO Ab), elevated serum thyrotropin, lymphocytic infiltration of the thyroid gland and presence of a goiter on clinical examination [1].


The most common cause of acquired hypothyroidism [1,2], sevenfold more common in women [1] with increasing incidence after the age of 45 [3].


There is a genetic predisposition for Hashimoto's thyroiditis, as patients with human leukocyte antigen (HLA) class I and class II (HLA-DR3, HLA-DR4, HLA-DR5), polymorphisms in the region of the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene on chromosome 2q33 or on chromosomes 6p, 13q32, 12q22 are more susceptible to the development of Hashimoto's thyroiditis [4].

Molecular and Systemic Pathophysiology

Hashimoto's thyroiditis is characterized by diffuse lymphocytic infiltration, gradual destruction of the gland and fibrosis. The size of the thyroid follicles is reduced and they contain sparse colloid. Although the follicles are small, the individual thyroid cells often appear enlarged and contain cytoplasm that is granular and pink (oxyphil change). Such cells are known as Hürthle or Askanazy cells [1].

The etiology of Hashimoto's thyroiditis remains unclear but genetic, environmental factors and immunotherapeutic agents are believed to contribute to their development [4].

It is believed that the autoimmune process begins with the activation of CD4 (helper) T lymphocytes that are specific for thyroid antigens. For this two mechanisms have been suggested. One hypothesis is referred to as molecular mimicry which postulates that an infection with a virus or bacterium containing a protein which is similar to a thyroid protein activates the thyroid-specific T-cells [1].

The other hypothesis proposes the induction of expression of major histocompatibility-complex (MHC) class II proteins by the affected thyrocytes as a major requirement for antigen presentation to CD4 T-cells [1,2,4].

When activated, reactive CD4 T-cells can stimulate cytotoxic (CD8) T-cells and recruit autoreactive B cells into the thyroid. Autoreactive B cells produce and secrete the TPO antibodies [1,2,4]. It is believed that the main mechanism responsible for hypothyroidism is the direct killing of thyroid cells by CD8 cells [1].

Nongenetic factors may be endogenous or exogenous. Endogenous factors such pregnancy are an important risk factor for autoimmune hypothyroidism [4]. Autoimmune throiditis is more common in geographic regions with the high intake of iodine which very likely increases the immunogenicity of thyroglobulin and thereby the prevalence of lymphocytic infiltration of the thyroid [1,4]. Drugs such as amiodarone, lithium and interferon-alfa have various effects on the immune system and thereby exacerbate autoimmune thyroiditis [1,4].

Diagnostic Principles

A test for TPO antibodies and measurement of the serum thyrotropin is generally sufficient to confirm the diagnosis [1]. The hallmark of chronic autoimmune thyroiditis is the presence of TPO autoantibodies [1].

Individuals with normal thyroid function, but TPO autoantibodies, may be at increased risk of progression to overt thyroid disease. In the Whickham follow-up study, women with thyroid autoantibodies had an eightfold higher likelihood of developing overt hypothyroidism over 20 years than did antibody-negative women [3].

The initial finding is a firm, symmetric, painless goiter [2]. The thyroid gland can be nonpalpabel or diffusely enlarged. Rarely, the gland can be painful and tender [1]. About 10% of patients have atrophic thyroid glands [2]. Patients may be hypothyroid or euthyroid. Or in some cases hyperthyroidism may alternate with hypothyroidism most likely due to the destruction of thyroid follicles with a transient release of thyroid hormones and the subsequent fibrosis of the organ. Moreover, transitions to Graves' disease are possible [1,2].

Ultrasonography typically shows a hypoechogenic pattern [1,2]. The thyroid scintigraphy does not show uptake and is unnecessary [1,2]. Thyroid-associated ophthalmopathy can occur but is not common [1].

Therapeutic Principles

If overt hypothyroidism or subclinical hypothyroidism with high TPO antibody concentrations is present which usually progresses to overt hypothyroidism and which may be associated with hyperlipidemia and atherosclerotic heart disease, levothyroxine sodium is the treatment of choice [2].

The goal of the replacement therapy is the normalization of serum thyrotropin values.

The TPO antibody concentration does not decrease with levothyroxine sodium therapy, except for some patients with hypothyroidism [2]. Irrespective of the initial serum thyrotropin concentration in patients with Hashimoto's thyroiditis and a large goiter, thyrotropin-suppressing doses of levothyroxine sodium can be given for a short term to decrease the size of the goiter. The goiter size will decrease by 30% after 6 months of therapy with levothyroxine sodium [2]. If the size of the goiter does not decrease replacement doses aiming at a normal TSH should be resumed [2].

Fine-needle aspiration biopsy is indicated if there is a dominant nodule or enlarged lymph nodes to rule out lymphoma and thyroid carcinoma [2].

Selenium (Se) supplementation may decrease TPO antibodies and improve the inflammatory activity [5].

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© Springer-Verlag GmbH Berlin Heidelberg 2009
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