On the Pathogenesis of Autoimmune Thyroid Disease: A Unifying Hypothesis

Stelios Fountoulakis; Agathocles Tsatsoulis


Clin Endocrinol. 2004;60(4) 

In This Article


Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland. The presently accepted classification of AITD, listed in Table 1 , includes chronic autoimmune thyroiditis or Hashimoto's thyroiditis (HT) and its variants (painless postpartum and sporadic thyroiditis), autoimmune atrophic thyroiditis or primary myxoedema and Graves' disease (GD). Investigation of the AITDs has focused on determining their pathogenesis and origin in order to develop specific aetiologically based therapeutic measures. Genetic and environmental factors appear to interact leading to appearance of autoantigens and accumulation of professional antigen-presenting cells (APCs) in the thyroid. Consequently, due to loss of immune tolerance, autoreactive immune cells activated by APCs, invade the thyroid gland interacting with thyroid cells in a battle for survival. The activation of apoptotic pathways through surface receptors and ligands is of great significance for the outcome of this battle and thus the clinical expression of AITD. The apoptotic pathways are regulated at several levels and normally remain inactive but blocking can be overcome after cell exposure to certain cytokines produced locally by the activated T lymphocytes. It is likely that the regulation of apoptosis during this interaction between the invading lymphocytes and the defending thyroid cells, may play an important role for the clinical expression of AITD.

In this article, current evidence regarding the mechanisms underlying the pathogenesis of AITD is reviewed. Particular emphasis is given to the role of iodine in inducing thyroid autoimmunity and, more importantly, to the role of apoptosis in determining the diverse clinical outcome following the disturbance in immune tolerance and the inappropriate activation of the immune system against the thyroid gland.


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