On the Pathogenesis of Autoimmune Thyroid Disease: A Unifying Hypothesis

Stelios Fountoulakis; Agathocles Tsatsoulis

Disclosures

Clin Endocrinol. 2004;60(4) 

In This Article

The Phenotypic Characteristics of AITDs

An accepted classification of thyroid-specific autoimmune diseases is shown in Table 1 and includes the various types of chronic autoimmune thyroiditis and GD (Pearce et al., 2003).

Chronic autoimmune thyroiditis is divided into HT and atrophic thyroiditis, based on clinical findings. HT is characterized by the presence of goitre, thyroid autoantibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg) in serum and varying degrees of thyroid dysfunction. It is considered to be the result of immune response which leads to aberrant infiltration of autoantigen-specific lymphoid cells and destruction of thyroid follicles. The intrathyroidal lymphocytes are both T and B lymphocytes, with Th-1 subtype predominating, although Th2 cells are also present (Roura-Mir et al., 1997; Battifora et al., 1998; Blüher et al., 1999). Lymphocytes occasionally form germinal centres in and around the follicular cells. The final outcome is hypothyroidism as a result of thyroid cell destruction.

On the other hand, atrophic thyroiditis is characterized by a small (atrophic) thyroid gland with lymphocytic infiltration and fibrous tissue replacing normal thyroid parenchyma and presents with clinical hypothyroidism. Antagonist antibodies to the TSH receptor are present in 20-50% of patients with atrophic thyroiditis, while such antibodies are also found in up to 10% of patients with goitrous thyroiditis and overt hypothyroidism (Orgiazzi, 2000). Another variant of autoimmune thyroiditis is painless (silent) thyroiditis with its sporadic and postpartum forms (Stagnaro-Green, 2002). These are usually transient but may recur, especially the postpartum form with subsequent pregnancies (Pearce et al., 2003). Silent thyroiditis is described as painless goitrous lymphocytic thyroiditis with antithyroid antibodies and a triphasic course with mild thyrotoxicosis followed by hypothyroidism and return to euthyroid state.

GD is characterized by follicular hyperplasia, patchy lymphocytic infiltration of the thyroid, not as massive as in HT, and occasional formation of lymphoid germinal centres (Armengol et al., 2001). The majority of thyroid infiltrating T lymphocytes act mainly as CD4+ Th2 cells although Th1 type cells are also present (Roura-Mir et al., 1997). GD is due to antibodies to the TSH receptor, which stimulate thyroid growth and function (Rees Smith et al., 1988; Rapoport et al., 1998). In a recent study, isolation of thyroid-stimulating monoclonal antibodies produced by lymphocytes from a patient with GD was made possible, a discovery that may advance our understanding of GD (Sanders et al., 2003).

Both GD and HT can present with similar findings including lymphocytic infiltration of the thyroid and anti-Tg and anti-TPO autoantibodies in the serum. The clinical course may also fluctuate between the two disorders. This observation can lead to the assumption that HT and GD may have a partially shared pathogenesis.

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