Autoimmune thyroid diseases

Many environmental factors have been implicated in the induction of autoimmunity. One dietary component, iodine, has been well studied as a factor that increases autoimmune thyroid disease.67 68 Based on studies in the OS chicken, the increasing prevalence of autoimmune thyroid disease observed in U.S. and Western European populations has been ascribed to increased use of iodized salt.69 Experimentally, it can be shown that iodinated thyroglobulin is a more potent autoantigen than the equivalent noniodinated molecule. Food additives or pesticides may also be important in contributing to the development of autoimmune disease in susceptible individuals.70... 

A recent report by the National Institutes of Health estimated that at 14 to 22 million people in the United States are affected by an autoimmune disease.1 As a group, these diseases represent a leading cause of death among women under age 65, with systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes being the major sources of this impact on mortality.2 The autoimmune thyroid diseases, type 1 diabetes and rheumatoid arthritis are the most common of the autoimmune diseases (Table 25.1).3-5 Most autoimmune diseases disproportionately affect women. In the thyroid diseases, primary biliary cirrhosis, scleroderma, systemic lupus erythematosus, and Sjogren s syndrome, more than 85% of patients are female, but it is not known why the female predominance is so high in these specific diseases. 

There have been occasional case-reports of infants with goiter and hypothyroidism associated with soy-based infant formula consumption (Tuohy, 2003). There has been one case control study, by Fort et al. (1990), which suggested a higher prevalence of soy-based formula feeding in infants with subsequent autoimmune thyroid disease. However, an alternative explanation may be a greater tendency for atopic infants (who may be more likely to be fed soy-based infant formulas) to have such antibodies. 

Fort, P., Moses, N., Fasano, M., Goldberg, T. and Lifshitz, F. (1990). Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children, J. Am. Coll. Nutr., 9, 164-167. 

Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism Interferon-a, interleukin-2, interferon-B, lithium, amiodarone... 

The complexity of the interaction between iodine intake and autoimmune thyroid disease has been highlighted by reports of evidence that iodide (compared with thyroxine) induces thyroid autoimmunity in patients with endemic (iodine deficient) goiter (43), while in those with pre-existing thyroid autoimmunity, evidenced by the presence of antithyroid (thyroid peroxidase) antibodies, administration of iodine in an area of mild iodine deficiency led to subclinical or overt hypothyroidism (44). 

The prevalence of ANCA, as measured by immunofluorescence, was significantly increased in those with Graves disease (20%) compared with euthyroid controls (4.6%), as was the prevalence of specific myeloperoxidase (MPO)-ANCA, measured by ELISA. The prevalence of ANCA was more strongly associated with propylthiouracil (RR = 7.3 Cl = 4.2,12.9) than carbimazole (RR = 2.2 Cl = 1.8, 2.8) when compared with controls, although there was still a positive association with carbimazole. ANCA positivity was not increased in patients with autoimmune thyroiditis. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not itself sufficient to increase the risk of development of ANCAs, but that thionamide therapy is required the risk is higher with propylthiouracil than with carbimazole. 

The second patient had other risk factors for autoimmune thyroid disease, and the association was probably coincidental, but the episode may have been precipitated by low estrogen concentrations, as is hypothesized in postpartum thyroiditis. 

Further reports of autoimmune thyroid disease in association with gonadorelin analogues have appeared (32). 

A 50-year-old woman with previous autoimmune thyroid disease taking atorvastatin developed acute hepatitis when she also was given ezetimibe (4). Further investigations, including liver biopsy, showed a probable drug-induced autoimmune hepatitis. 

The immunological predisposition to thyroid disorders has been studied in 17 of 439 Japanese patients who had symptomatic autoimmune thyroid disorders during interferon alfa treatment (521). There was a significantly higher incidence of the human leukocyte antigen (HLA)-A2 hap-lotype compared with the general Japanese population (88 versus 41%), suggesting that HLA-A2 is a possible additional risk factor for the development of interferon alfa-induced autoimmune thyroid disease. 

Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, Weetman A, Hale G, Chatteqee VK, Waldmann H, Compston A. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 1999 354(9191) 1691-5. 

Prummel MF, Laurberg P. Interferon-alfa and autoimmune thyroid disease. Thyroid 2003 13 547-51. 

Schuppert F, Rambusch E, Kirchner H, Atzpodien J, Kohn LD, von zur Muhlen A. Patients treated with interferon-alpha, interferon-beta, and interleukin-2 have a different thyroid autoantibody pattern than patients suffering from endogenous autoimmune thyroid disease. Thyroid 1997 7(6) 837-42. 

Fernandez-Soto L, Gonzalez A, Escobar-Jimenez F, Vazquez R, Ocete E, Olea N, Salmeron J. Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy. Arch Intern Med 1998 158(13) 1445-8. 

Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism... 

Zimmer KP, Schmid KW, Bocker W, et al. Transcytosis of IgG from the basolateral to the apical membrane of human thyrocytes in autoimmune thyroid disease. Cun-... 

Addisons disease, results from progressive destruction or dysfunction of the adrenal glands by a local disease process or systemic disorder (Box 51-12), Worldwide, infectious diseases are the most common cause of primary adrenal insufficiency and include tuberculosis, fongal infections (histoplasmosis and cryptococcosis), and cytomegalovirus infections. Autoimmune adrenalitis accounts for more than 70% of cases reported in the Western world, with adrenal autoantibodies noted in more than 75% of cases,. The adrenal glands are atrophic, with loss of cortical cells but an intact medulla. Almost 50% of patients with autoimmune adrenalitis have an associated autoimmune disease with autoimmune thyroid disease the most common. 

D. T4 binding by antibodies (autoimmune thyroid disease, hepatocellular carcinoma)... 

The measurement of TgAb adds little diagnostic information over and above TPOAb measurement for diagnosing autoimmune thyroid disease. " However, measurement of TgAb is needed to identify sera with autoantibodies that may interfere with serum Tg measurements in patients being managed for treatment of thyroid carcinoma. 

S. M. McLachlan and B. Rapoport The molecular biology of thyroid peroxidase cloning, expression and role as autoantigen in autoimmune thyroid disease. Endocrine Review 13,192 (1992). 

A. P. Weetman and A. M. McGregor Autoimmune thyroid disease further developments in our understanding. Endocrine Review 15, 788 (1994). 

Mukuta T, Yoshikawa N, Arreaza G, et al. Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. J CUn Endocrinol Metab 1995 80 1264-1272. 

APGS type 2, also referred to as Schmidt syndrome, is characterized by Addison disease in association with autoimmune thyroid diseases and/or diabetes mellitus type 1. APGS type 2 may occur at any age and in both sexes (the female to male ratio is 2 1), but it is most common in middle-aged females and very rare in childhood. Several studies have revealed an association of this syndrome with various alleles within the HLA-DR3-canying haplotype. 

The least well characterized autoimmune polyglandular syndrome is the type 3 syndrome. This syndrome is defined by the presence of autoimmune thyroid disease with another autoimmune disease, such as diabetes mellitus type l, autoimmune gastritis, or myasthenia gravis, but in the absence of Addison disease. APGS type 3 primarily involves females (the female to male ratio is 7 1) who have HLA-DR3-associated autoimmune disease and is probably the most common of the autoimmune polyglandular syndrome disorders. Since different and multiple clinical combinations can be found, the classification of this type of autoimmune polyglandular syndrome is probably more complicated than originally anticipated. 

The autoimmune thyroid diseases, including Graves disease and Hashimoto thyroiditis, are some of the most common human autoimmune diseases (Pearce et al., 2003). These diseases are characterized by immune responses to thyroid antigen, resulting in infiltration of the thyroid by T cells and production of thyroid antibodies. However, the manifestations of these two entities are clearly different, and the two diseases are discussed separately. Furthermore, the effect of iodine supplementation on thyroiditis is discussed briefly. 

Almost all autoimmune diseases that occur in adults disproportionately affect women. However, there is considerable variability in the extent of female predominance and no clear relation between degree of female predominance and type of disease or age at onset (Table 7). More than 85% of patients with Sjogren syndrome, systemic lupus erythematosus, systemic sclerosis, the autoimmune thyroid diseases, and primary biliary cirrhosis are female, compared with 65-75% of patients with rheumatoid arthritis and multiple sclerosis. Some diseases (e.g. diabetes mellitus type 1, ANCA-associated vasculitis, primary sclerosing cholangitis) occur more often in males than in females. 

Data pertaining to co-morbidity of autoimmune diseases in humans are surprisingly sparse. Few studies are population-based, and few are of sufficient size to address potentially important biological associations, given the relative rarity of many diseases (Scofield, 1996). A recent unpublished review of co-morbidity of rheumatoid arthritis, diabetes mellitus type 1, multiple sclerosis, Crohn disease, and autoimmune thyroid disease found evidence of an increased incidence of autoimmune thyroid disease in patients with rheumatoid arthritis and in autoimmune diabetes (E. Somers, unpublished data). 

Studies of autoantibodies in the general population allow us to determine the prevalence of specific autoantibodies among people who do not have a clinically evident autoimmune disease, whether the prevalence of autoantibodies reflects the demographic variation in disease risk and whether specific environmental exposures are related to the expression of specific autoantibodies. These studies are most feasible for the autoantibodies associated with the most common autoimmune diseases diabetes mellitus type 1, autoimmune thyroid disease, and rheumatoid arthritis. Important issues with respect to interpreting these types of studies include the type of test used and definition of a positive result. 

---