Home > E. Pathology by systems > Endocrine system > Thyroid > Hashimoto thyroiditis

Hashimoto thyroiditis

MIM.140300

Thursday 12 January 2006

Hashimoto’s thyroiditis; Struma lymphomatosa (lymphocytic thyroiditis); chronic lymphocytic thyroiditis, Hashimoto thyroiditis, thyroid autoimmunity

Digital case

- HPC:306 : Thyroid marginal zone B-cell lymphoma (Thyroid MALT lymphoma) and lymphocytic thyroiditis.
- JRC:18915 : Struma lymphomatosa (lymphocytic thyroiditis)

Definition: Hashimoto thyroiditis (or chronic lymphocytic thyroiditis) is the most common cause of hypothyroidism in areas of the world where iodine levels are sufficient. It is characterized by gradual thyroid failure because of autoimmune destruction of the thyroid gland. The name Hashimoto thyroiditis is derived from the 1912 report by Hashimoto describing patients with goiter and intense lymphocytic infiltration of the thyroid (struma lymphomatosa).

This disorder is most prevalent between 45 and 65 years of age and is more common in women than in men, with a female predominance of 10:1 to 20:1. Although it is primarily a disease of older women, it can occur in children and is a major cause of nonendemic goiter in children.

Epidemiologic studies have demonstrated a significant genetic component to Hashimoto thyroiditis, although, as in most other autoimmune disorders, the pattern of inheritance is non-Mendelian and likely to be influenced by subtle variations in the functions of multiple genes.

The concordance rate in monozygotic twins is 30% to 60%, and up to 50% of asymptomatic first-degree relatives of Hashimoto patients demonstrate circulating antithyroid antibodies.

Several chromosomal abnormalities have been associated with thyroid autoimmunity. For example, adults with Turner syndrome have a high prevalence of circulating antithyroid antibodies, and a substantial minority (∼20%) develops subclinical or clinical hypothyroidism that is indistinguishable from Hashimoto thyroiditis. Similarly, adults with trisomy 21 (Down syndrome) are also at an increased risk for developing Hashimoto thyroiditis and hypothyroidism.

There are reports that polymorphisms in the HLA locus, specifically the HLA-DR3 and HLA-DR5 alleles, are linked to Hashimoto thyroiditis, but the association is weak. Finally, genomewide linkage analyses in families with Hashimoto thyroiditis have provided evidence for several susceptibility loci, such as on chromosomes 6p and 12q, that may harbor genes predisposing to this disorder.

Pathogenesis

Hashimoto thyroiditis is an autoimmune disease in which the immune system reacts against a variety of thyroid antigens. The overriding feature of Hashimoto thyroiditis is progressive depletion of thyroid epithelial cells (thyrocytes), which are gradually replaced by mononuclear cell infiltration and fibrosis.

Multiple immunologic mechanisms may contribute to the death of thyrocytes. Sensitization of autoreactive CD4+ T-helper cells to thyroid antigens appears to be the initiating event.

The effector mechanisms for thyrocyte death include the following:

- CD8+ cytotoxic T cell-mediated cell death: CD8+ cytotoxic T cells may cause thyrocyte destruction by one of two pathways: exocytosis of perforin/granzyme granules or engagement of death receptors, specifically CD95 (also known as Fas) on the target cell.

- Cytokine-mediated cell death: CD4+ T cells produce inflammatory cytokines such as IFN-γ in the immediate thyrocyte milieu, with resultant recruitment and activation of macrophages and damage to follicles.

- Binding of antithyroid antibodies (anti-TSH receptor antibodies, antithyroglobulin, and antithyroid peroxidase antibodies) followed by antibody-dependent cell-mediated cytotoxicity (ADCC).

Synospsis

- interstitial lymphocytic infiltration
- interstitial fibrosis
- defect in thyroid basement membrane
- +/- Hashimoto tyroiditis-associated papillary thyroid carcinoma (#17660159#)

Morphology

The thyroid is often diffusely enlarged, although more localized enlargement may be seen in some cases. The capsule is intact, and the gland is well demarcated from adjacent structures. The cut surface is pale, yellow-tan, firm, and somewhat nodular.

Microscopic examination reveals extensive infiltration of the parenchyma by a mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells, and well-developed germinal centers.

The thyroid follicles are atrophic and are lined in many areas by epithelial cells distinguished by the presence of abundant eosinophilic, granular cytoplasm, termed Hürthle cells. This is a metaplastic response of the normally low cuboidal follicular epithelium to ongoing injury.

In fine-needle aspiration biopsies, the presence of Hürthle cells in conjunction with a heterogeneous population of lymphocytes is characteristic of Hashimoto thyroiditis.

In "classic" Hashimoto thyroiditis, interstitial connective tissue is increased and may be abundant. A fibrous variant is characterized by severe thyroid follicular atrophy and dense "keloid-like" fibrosis, with broad bands of acellular collagen encompassing residual thyroid tissue. Unlike Reidel thyroiditis (see below), the fibrosis does not extend beyond the capsule of the gland.

The remnant thyroid parenchyma demonstrates features of chronic lymphocytic thyroiditis.

Clinical Course

Hashimoto thyroiditis comes to clinical attention as painless enlargement of the thyroid, usually associated with some degree of hypothyroidism, in a middle-aged woman.

The enlargement of the gland is usually symmetric and diffuse, but in some cases, it may be sufficiently localized to raise a suspicion of neoplasm. In the usual clinical course, hypothyroidism develops gradually.

In some cases, however, it may be preceded by transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones ("hashitoxicosis").

During this phase, free T4 and T3 levels are elevated, TSH is diminished, and radioactive iodine uptake is decreased. As hypothyroidism supervenes, T4 and T3 levels progressively fall, accompanied by a compensatory increase in TSH.

Patients with Hashimoto thyroiditis are at increased risk for developing other concomitant autoimmune diseases, both endocrine (type 1 diabetes, autoimmune adrenalitis), and nonendocrine (systemic lupus erythematosus, myasthenia gravis, and Sjögren syndrome, and also at increased risk for the development of B-cell non-Hodgkin lymphomas.

However, there is no established risk for developing thyroid epithelial neoplasms.

Biology

- thyroid autoantibodies

  • anti-microsme antibodies

- abnormal, small, iodinated protein in the serum

Predisposition

- autosomal dominant inheritance

- Locus 2q33: CTLA4 (MIM.123890)
- Locus 6p11: AITD1 (MIM.608173)
- Locus 5q31-q33: AITD2 (MIM.608174)
- Locus 8q24: AITD3 (MIM.608175)
- Locus 10q: AITD4 (MIM.608176)
- Locus 18q21: AITD5 (MIM.601941)

References

- Paolieri F, Pronzato C, Battifora M, Fiorino N, Canonica GW, Bagnasco M. Infiltrating gamma/delta T-cell receptor-positive lymphocytes in Hashimoto’s thyroiditis, Graves’ disease and papillary thyroid cancer. J Endocrinol Invest. 1995 Apr;18(4):295-8. PMID: #7560812#

Portfolio

  • Hashimoto thyroiditis with thyroid follicular adenoma
  • Hashimoto thyroiditis with thyroid follicular adenoma
  • Hashimoto thyroiditis with thyroid follicular adenoma
  • Hashimoto thyroiditis with thyroid follicular adenoma
  • Hashimoto thyroiditis with thyroid follicular adenoma