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مواضيع متنوعة أخرى

الانزيمات
Thyroglobulin and Thyroid Peroxidase Antibodies
المؤلف:
Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).
المصدر:
Oxford Textbook of Endocrinology and Diabetes
الجزء والصفحة:
3rd edition , p440-441
2026-04-07
20
There are essentially four methods for assaying thyroglobulin and thyroid peroxidase antibodies. The two oldest are haemagglutination and indirect immunofluorescence, which depend on dilution of the test serum to determine the level of antibodies. Although robust and providing reasonably sensitive and specific results, the more modern methods of enzyme- linked immunosorbent assay (ELISA) and radioimmunoassay allow truly quantitative determination of antibodies and, in the case of assays for thyroid per oxidase antibodies, can use antigen of high purity, if necessary for research purposes. Thyroid peroxidase was previously called the microsomal antigen, and assays for these antibodies have relied on positive immunofluorescence staining with an appropriate pattern or, in the case of haemagglutination, have used an excess of thyroglobulin to absorb out thyroglobulin antibody activity when testing crude microsomal extracts of thyroid homogenate. Comparison of assays based on haemagglutination with microsomal antigen and more modern methods with purified or even recombinant thy roid peroxidase has shown a good correlation between the two, although those assays based on thyroid peroxidase are more sensitive. Further improvement in assay standardization has come from the use of reference positive serum samples, and increased sensitivity has been achieved with the use of immunometric as says, which are now automated, utilize chemiluminescence, and are widely available. Nonetheless there are still significant differences in the cut- offs for positivity between assay kits from different manufacturer.
With the most sensitive assays, up to 20% of healthy women have thyroglobulin and/ or thyroid peroxidase antibodies, although in the majority the levels are very low. Using more conventional assays, 11% of women and 3% of men were positive in a large community- based survey in the United Kingdom and similar results have been reported elsewhere. Antibodies are not entirely stable, appearing or disappearing in 17% and 2% of women, respectively, over a 20- year period. In healthy individuals, the presence of such antibodies is a marker of future thyroid dysfunction, especially if coupled with subclinical hypothyroidism, and all patients with positive thyroid antibodies should be offered annual screening to detect early thyroid failure, while patients with subclinical hypothyroidism should have antibodies measured to stratify their risk.
Thyroid peroxidase antibodies are found in 80– 90% of Graves’ sera and 95– 100% of Hashimoto sera, with thyroglobulin antibodies in up to 70% of Graves’ and 90– 100% of Hashimoto sera, using sensitive assays. Occasional patients with Hashimoto’s thyroiditis are negative for serum thyroid antibodies, although synthesis can usually be detected locally within the thyroid, presumably at too low a level to be detectable in serum. In most patients, thyroglobulin antibodies are accompanied by thyroid peroxidase antibodies, but some patients only have one or the other type.
Thyroglobulin and thyroid peroxidase antibodies are found in a variety of other conditions at higher frequency than would be expected by chance (Box 1).
Box1. Conditions associated with an increased prevalence of thyroglobulin and thyroid peroxidase antibodies
Antibody testing is certainly useful in patients with Addison’s disease, as around 25% may develop thyroid dysfunction due to as sociated autoimmune polyglandular syndrome type 2. Similar considerations apply to pernicious anaemia, coeliac disease and, more debatably, other autoimmune disorders which are associated with a high frequency of thyroid autoimmunity. Another situation where prospective thyroid antibody testing is particularly worth while is in patients starting amiodarone, as those with antibodies are more likely to develop amiodarone- induced hypothyroidism. The presence of thyroid antibodies is also useful in predicting the risk of thyroid dysfunction after treatment with γ- interferon.
On the other hand, measurement of thyroid antibodies can be misleading in goitre, as patients with multinodular goitre can have thyroid antibodies in association with focal thyroiditis, although the antibodies are usually only at low or moderate levels. Similarly, around 25% of patients with papillary or follicular thyroid cancer have thyroglobulin and/ or thyroid peroxidase antibodies. There does appear to be an association between Hashimoto’s thyroiditis and differentiated thyroid cancer, as well as with lymphoma: there is controversy regarding the prognostic value of thyroglobulin anti bodies in thyroid cancer, possibly related to epitope recognition differences and the assays used. Such antibodies can interfere with the assay of thyroglobulin in thyroid cancer follow- up.
Thyroid peroxidase antibody positivity is strongly related to postpartum thyroiditis, giving rise to the suggestion that it may be worthwhile screening all pregnant women antepartum, but the positive predictive value of thyroid peroxidase antibodies is quite low and some cases have been reported in women who are thyroid peroxidase antibody- negative. Universal screening is not currently recommended, although the TSH should be checked in all pregnant women already known to be thyroid antibody- positive. Because of the high frequency of postpartum thyroiditis in type 1 diabetes mellitus and other autoimmune disorders, there is a strong case for TSH measurement (and thyroid peroxidase antibody screening if the TSH exceeds 2.5 mU/ L) in this group of women antepartum. Women with positive thyroid antibodies, even without clinical thy roid dysfunction, are at risk of recurrent first trimester miscarriage, but it seems that early thyroxine treatment may not have the bene fits that were originally predicted in this group. There is also evidence that the presence of thyroid antibodies, in the absence of an elevated TSH, may be associated with a lack of well- being, depression, and even rare cases of encephalopathy. Whether these associations are due to a direct effect of the antibodies, or the underlying effects of an autoimmune response, is not known.
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