Thyroid antibodies are present in increased prevalence (up to 32%) in patients with carcinoma of the thyroid, and usually are at low titer. Histologic evidence of thyroiditis is found in 26% of tumors (382, 383). Histologic changes range from diffuse thyroiditis to focal collections of lymphocytes around the tumor or reactive lymphoid hyperplasia. Possibly release of antigens leads to increased thyroid autoimmunity. Some evidence suggests that patients who have thyroid antibodies have a better prognosis than antibody negative patients. Lymphoma and lymphosarcoma of the thyroid are associated with Hashimoto's thyroiditis (383-385), and there is compelling evidence that thyroiditis precedes development of the tumor. An increased frequency of carcinoma, especially of the papillary type, has been suggested in Hashimoto's thyroiditis (386). Our experience does not indicate an association greater than that dictated by chance. Woolner et al (383), in a study of 600 cases, reached the same conclusion. It is also possible that focal thyroiditis in thyroid cancer represents a secondary immune response to the tumor.

Enlargement of the thyroid during the second decade, accompanied by normal results of function tests, usually is labeled adolescent goiter. If the examination includes needle biopsy, an appreciable incidence of Hashimoto's thyroiditis is found (387) - up to 65%. Eighty percent of these children with thyroiditis have a positive thyroid antibody test result. The parents of many of them have either overt thyroid disease or circulating thyroid antibodies. Hyperplasia, in response to an increased demand for thyroid hormone, and colloid involution are at the root of some of these goiters, but Hashimoto's thyroiditis is the most frequent explanation of adolescent goiter in iodine sufficient areas.

These illnesses, all similar, involve an acute exacerbation of thyroid autoimmunity occurring independent of, or following pregnancy in women, and in men. They are characterized by sequential inflammation-induced T ₄and TG release, transient hypothyroidism, usually return to euthyroidism, and are discussed in Chapters 8 and 14. A useful review of these various types of thyroiditis has also appeared recently (388). They are considered subtypes of Hashimoto's thyroiditis, and in the postpartum period, appear to result from release of the immunoinhibitory effects of normal pregnancy.

Focal lymphocytic infiltrations are frequently seen in Graves' disease, nodular goiter, nontoxic or colloid goiter, and thyroid carcinoma. The significance of these changes is not precisely known, but they correlate with positive antibody titers and may represent variations that do not differ qualitatively from thyroiditis.

An association between the occurrence of maternal antithyroid antibodies and recurrent abortion has been reported (389) and although this association has been disputed, a recent study showed clear evidence that the presence of TPO antibodies was associated with a 3-4-fold increased risk of miscarriage in women having in vitro fertilization (390). There is also an association between breast cancer and thyroid autoimmunity (391, 392) and between depression in middle-aged women and the presence of TPO antibodies (393). The nature of these associations is unclear; does thyroid autoimmunity predispose to such adverse events, or is the presence of thyroid autoimmunity simply a marker of a non-specific disturbance in the immune system due to whatever has caused miscarriage, cancer or depression?