Thyroid autoantibodies

Belin, R.M. et al., Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III), J. Clin. Endocrinol. Metab., 89, 6077, 2004. 

Possible mechanisms need to be clarified. Since thyroid autoantibodies are detected in most patients who develop thyroid disorders, the induction or exacerbation of preexisting latent thyroid autoimmunity is the most attractive hypothesis. This is in accordance with the relatively frequent occurrence of other autoantibodies or clinical autoimmune disorders in patients who develop thyroid disorders (514). However, 20-30% of patients who develop thyroid diseases have no thyroid antibodies, and it is thus not yet proven that autoimmunity is the universal or primary mechanism. In fact, there were subtle and reversible defects in the intrathyroidal organification of... 

Amato G. Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment. J Clin Endocrinol Metab 2001 86(5) 1925-9. 

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. 

Carella C, Mazziotti G, Morisco F, Rotondi M, Cioffi M, Tuccillo C, Sorvillo F, Caporaso N, Amato G. The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism. Eur J Endocrinol 2002 146(6) 743-9. 

Crowe, XR, Christensen, E., Butler, X, Wheeler, R, Doniach, D., Keenan, X, Williams, R. Primary biliary cirrhosis the prevalence of hypothyroidism and its relationship to thyroid autoantibodies and sicca syndrome. Gastroenterology 1980, 78 1437-1441... 

Autoimmune thyroiditis (AITD) is one of the most common autoimmune disorders. The humoral immune response is dominant in Graves hyperthyroidism, whereas cellular immune response is more dominant in hypothyroidism caused by chronic AITD (Marcocci and Chiovato, 2000). Thyroid autoantibodies are proteins manufactured by the immune system that are directed against proteins in the thyroid. Although nearly all patients with chronic... 

AITD have high concentrations of circulating thyroid autoantibodies (Arai et ai, 2000 Carle et aL, 2006 Feldt-Rasmussen, 1996), for the most part the disorder appears to be the consequence of tissue damage initiated by T lymphocytes (Weetman and McGregor, 1994). Measurement of autoantibodies against thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) has for many years been a major tool in the diagnosis of autoimmune thyroid diseases, such as Hashimotos thyroiditis, primary myxedema and postpartum thyroiditis (Feldt-Rasmussen et ai, 1991 Feldt-Rasmussen, 1996). 

Human Tg is one of the main autoantigenes in thyroid disease caused by AITD (Salvi et aL, 1988), but antibodies against Tg are also frequently measurable in serum from apparently healthy subjects from the population (Hollowell et aL, 1998 Pedersen et aL, 2003). lodination of Tg may induce major changes in its stereochemical configuration (Dunn et aL, 1983), which may change its immunoreactivity and be important in the generation of thyroid autoantibodies (Saboori et aL, 1998). 

The other problem is the differences in the epidemiological methods applied. It is well-established that thyroid autoantibodies are more commonly measurable in females than in males (Hollowell et al., 1998 Laurberg et ai, 1998 Prentice et al., 1990 Tunbridge et ai, 1977), and that the prevalence of antibodies increases with age, at least in females (Pedersen et al, 2003). It is possible that this increase is present only up to a certain age, after which there may be a plateau (Aghini-Lombardi et al, 1999 Hawkins et al, 1980 Tunbridge et al, 1977). The results obtained from the population studies should therefore be age and sex standardized before comparison. Some studies included highly selective participants, such as subjects above 70 years... 

Comparison of epidemiological studies on the prevalence of circulating thyroid autoantibodies in areas with different iodine intakes is therefore difficult, unless the studies are designed as comparatives with exactly the same methods applied in two or more regions. 

Five years after the introduction of iodized salt in Sri Lanka, the prevalence of Tg-Ab was high among schoolchildren. The interpretation of the authors was that this was the result of the increased iodine intake (Premawardhana et al., 2000). Three years later, when the status was re-evaluated, the prevalence of Tg-Ab had decreased significandy (Mazziotti et ai, 2003). Unfortunately, no pre-iodine data on thyroid autoantibodies were available. 

As described previously, it is difficult to compare the results from different studies on prevalence rates of circulation thyroid autoantibodies. Unfortunately, there are relatively few comparative studies of cohorts with different iodine intake in which sensitive assays have been applied in the analysis of thyroid autoantibodies. 

Table 60.1 Thyroid autoantibodies in population studies from areas with different iodine intake ...

A number of studies on the epidemiology of thyroid autoantibodies have been performed as descriptive studies in iodine-deficient areas. Results from some population-based studies from both iodine-deficient and iodine-sufficient areas are shown in Table 60.1. The results are ambiguous. 

In the original Wickham study, thyroid autoantibodies were measured in 2779 subjects from the small city, Wickham, in the UK (Tunbridge etai, 1977). Both Tg-Ab and Mic-Ab were measured with old assays with relatively low sensitivity. The prevalence of one or both antibodies was 11.2% in females and 2.8% in males. At the followup 20 years later, 26.4% of the participants were antibody positive (Vanderpump et ai, 1996). Possible explanations... 

A sudden increase in iodine intake in an iodine-deficient population may induce enhanced thyroid autoimmunity (Harach and Williams, 1995). Both cellular immune response with histological signs of thyroiditis and humoral immune response with circulating thyroid autoantibodies may be increased. It seems as if at least a part of this autoimmunity is reversible, and that the prevalence of antibodies will decrease to a lower level over time if the higher iodine intake is continued (Mazziotti et al., 2003 Zimmermann et al., 2003), or decrease in a relatively short time period if the iodine intake is reduced to the basefine level (Kahaly et al.y 1998). 

In mild and moderate ID, the prevalence rate of circulating thyroid autoantibodies in the population is also high (Laurberg et ai, 1998 Pedersen et aL, 2003). In such areas, non toxic and toxic multinodular goiters are prevalent and overall hyperthyroidism is more common than hypothyroidism (Laurberg et ai, 1999). Results from areas with severe ID are fimited and might, in some cases, be influenced by the general immunosuppressive effect of malnutrition, which may occur simultaneously (Salabe et al., 1982). 

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