The serum TSH concentration is increased in primary hypothyroidism because of a loss of feedback inhibition of thyrotropin-releasing hormone (TRH) and TSH production by the hypothalamus and pituitary, respectively. The TSH concentration is not increased in individuals with hypothyroidism caused by primary hypothalamic or pituitary disease. Serum T4 is decreased in patients with hypothyroidism of any origin.
Autoimmunity is the underlying cause of a variety of thyroid diseases, which are collectively referred to as autoimmune thyroid disease (AITD). These disorders include thyroiditis, and antibody-mediated disturbances in thyroid function that are not necessarily associated with inflammation (exemplified by Graves disease). We discuss first the various forms of thyroiditis.
Thyroiditis encompasses a diverse group of disorders characterized by some form of thyroid inflammation. This discussion focuses on the three most common and clinically significant subtypes: (1) Hashimoto thyroiditis, (2) granulomatous (de Quervain) thyroiditis, and (3) subacute lymphocytic thyroiditis.
Hashimoto 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 secondary to autoimmune destruction of the thyroid gland. It is most prevalent between 45 and 65 years of age and is more common in women with a female to male ratio of 10:1 to 20:1. Although it is primarily a disease of older women, it can occur at any age, including childhood.
Hashimoto thyroiditis is an autoimmune disease caused by an immune response to thyroid autoantigens (Chapter 5). Circulating autoantibodies against thyroid antigens are present in the vast majority of patients. The immune response leads to progressive depletion of thyroid epithelial cells associated with lymphocytic infiltrates and fibrosis. The inciting events leading to the autoimmune response have not been fully elucidated, but multiple immunologic mechanisms that may contribute to thyroid cell damage have been identified (
Fig. 20.8 ), including the following:
CD8+ cytotoxic T-cell–mediated killing of thyroid epithelial cells.
Cytokine-mediated cell death. T-cell activation leads to the production of inflammatory cytokines such as interferon-γ in the thyroid gland, with resultant recruitment and activation of macrophages and damage to follicles.
Binding of anti-thyroid antibodies (anti-thyroglobulin, and anti-thyroid peroxidase antibodies), followed by antibody-dependent cell–mediated cytotoxicity (Chapter 5).
The disease appears to have a significant genetic component, based on a concordance rate of about 40% in mono-zygotic twins and the presence of anti-thyroid antibodies in approximately 50% of asymptomatic siblings of affected patients. Increased susceptibility to Hashimoto thyroiditis is associated with polymorphisms in immune regulation– associated genes, the most significant of which is the cytotoxic T lymphocyte–associated antigen-4 gene (CTLA4), which codes for a negative regulator of T-cell responses (Chapter 5).
MORPHOLOGYThethyroidusuallyisdiffuselyandsymmetricallyenlarged.Microscopicexaminationrevealswidespreadinfiltrationoftheparenchymabyamononuclearinflammatoryinfiltratecontainingsmalllymphocytes,plasmacells,andwell-developed http://ebooksmedicine.net
Breakdown in self-tolerance and induction of thyroid autoimmunity