Ovarian function after radioiodine therapy in patients with thyroid cancer.

OBJECTIVE: To assess ovarian function in young women treated with radioiodine. METHODS: The study was conducted on 50 women with thyroid carcinoma aged less than 40 years (mean, 29.8 years), with regular menstrual cycles and normal FSH levels prior to radioiodine therapy. FSH determination was repeated 6 and 12 months after radioiodine therapy (mean, 4.24 GBq iodine-131) and menstrual cycles were monitored during this period. RESULTS: Twenty percent of the patients reported amenorrhea during the first year. FSH levels increased after 6 months (from 5.1 +/- 1.8 to 10.6 +/- 2.2 IU/l, p < 0.00 001) and 28 % of the patients showed elevated values, which had returned to normal by the end of the first year. CONCLUSION: Radioiodine causes transitory alterations in ovarian function even in younger women and after a mean activity of 4.2 GBq (115 mCi).

Immunosuppression of thyroiditis.

Immunization of mice with 50 micrograms human thyroglobulin (TG) in complete Freund's adjuvant leads to histological thyroiditis; production of IgG, IgA, and IgM anti-TG antibodies; and in vitro proliferative responses after incubation of lymphocytes with TG. Oral administration of 500 micrograms TG at four intervals before Tg immunization and once afterward causes up to 80% suppression of these responses. The effect is antigen specific and dose dependent. Feeding TG after immunization produces a 40% reduction in responses. We wished to define the mechanism of this antigen-specific oral tolerization. Popliteal lymph nodes (PLN) of orally tolerized animals (T) are reduced in size compared to those in immunized (I) animals not fed TG. PLN and mesenteric lymph nodes (MLN) of I animals produce interleukin-2 (IL-2) and interferon-gamma (IFN gamma) after in vitro incubation with TG, typical of an inflammatory immune response. PLN and MLN of tolerized animals do not proliferate in response to antigen, do not produce IL-2 or IFN gamma, but do not produce the cytokines IL-4 and transforming growth factor-beta (TGF beta). Mixing in vitro of spleen cells from T and I animals causes a reduction in the immune response when incubated with TG, but no reduction in response to purified protein derivative (PPD) (the antigen in complete Freund's adjuvant). When T splenocytes are incubated with TG and PPD together, the response to TG and PPD is suppressed. Partially purified CD8+ cells from tolerized animals produce IL-4 and TGF beta after exposure to human TG and induce suppression, whereas partially purified CD4+ cells produce IL-2 and IFN gamma and do not cause suppression. MLN cells do not proliferate in response to antigen, but do produce inhibitory cytokines. T animals appear to shift the immune response from a Th-1 helper cell subset response to a Th-2 helper cell immunosuppressive response. In this model, oral tolerization produces a dramatic reduction in the immune response. Exposure of MLN to oral TG appears to cause the production of regulatory cells that migrate to spleen and PLN. In vitro studies demonstrate that on exposure to antigen, these regulatory cells produce IL-4 and TGF beta, which suppress all aspects of specific immune responsiveness and nonspecifically suppress other ongoing immune responses (bystander effect). Oral tolerization may include some element of T cell deletion or anergy. This model defines an experimental system with possible relevance to immunosuppression of human autoimmune thyroid disease.

Suppression of development of experimental autoimmune thyroiditis by oral administration of thyroglobulin.

Experimental autoimmune thyroiditis (EAT), which to some extent represents an experimental model of human chronic lymphocytic thyroiditis, is an organ-specific autoimmune disease characterized by autoantibody production to thyroid antigens (Ag) and mononuclear infiltration of the thyroid gland. EAT induced by immunization with human thyroglobulin (hTG) with Freund's adjuvant in CBA/J (H-2K) mice is associated with prominent B and T cell responses. We report that oral administration of hTG effectively reduces the immune responses in EAT in mice in an Ag-specific manner. Both cellular and humoral immune responses are reduced in a dose-dependent manner. Histological evidence of disease is dramatically reduced. Suppression of the immune responses is seen 2 weeks after Ag challenge, with partial inhibition of proliferative and antibody responses. Six weeks after immunization, further inhibition is observed of both T and B cell responses. Hyporesponsiveness of T and B cell reactivity is seen only to hTG; T and B cell responses to other immunogens are not affected, including purified protein derivative and the nonrelated Ag BSA. This model may provide the basis for immunotherapy of autoimmune thyroid diseases in man.