TSH, thyroid-stimulating hormone; ATP, adenosine triphosphate values should be aware of their limitations in the setting of acute illness, central hypothyroidism, the presence of heterophile antibodies, and TSH autoantibodies. In the setting of heterophile antibodies or TSH autoantibodies, TSH values will be falsely elevated (342). In cases of central hypothyroidism, decreased sialylation of TSH results in a longer half-life and a reduction in bioactivity (346,347). TSH levels may be elevated or normal when the patient remains clinically hypothyroid in states of central hypothyroidism, and successful treatment is often associated with low or undetectable TSH levels.
Many antigen–antibody reactions affecting the thyroid gland can be detected. Antibodies to TgAb, the TSH receptor (TSHRAb), TPOAb, the sodium iodine symporter (NISAb), and to thyroid hormone were identified and implicated in autoimmune thyroid disease states (348). A number of recognized thyroid autoantigens are listed in Table 31.10. Antibody production to thyroglobulin depends on a breach in normal immune surveillance (349,350). The incidence of thyroid autoantibodies in various autoimmune thyroid disorders is shown in Table 31.11.
Antithyroglobulin antibodies are predominantly in the noncomplement fixing, polycolonal, immunoglobulin-G (IgG) class. Antithyroglobulin antibodies are found in 35% to 60% of patients with hypothyroid autoimmune thyroiditis, 12% to 30% of patients with Graves disease, and 3% of the general population (351–353). Antithyroglobulin antibodies are associated with acute thyroiditis, nontoxic goiter, and thyroid cancer (348).
Previously referred to as antimicrosomal antibodies, TPO antibodies are directed against thyroid peroxidase and are found in Hashimoto thyroiditis, Graves disease, and postpartum thyroiditis. The antibodies produced are characteristically cytotoxic, complement-fixing IgG antibodies. In patients with thyroid autoantibodies, 99% will have positive anti-TPO antibodies, whereas only 36% will have positive antithyroglobulin antibodies, making anti-TPO a more sensitive test for autoimmune thyroid disease (353). Anti-TPO antibodies are present in 80% to 99% of patients with hypothyroid autoimmune thyroiditis, 45% to 80% of patients with Graves disease, and 10% to 15% of the general population (352–354). These antibodies can cause artifact in the measurement of thyroid hormone levels. Antithyroid peroxidase antibodies are used clinically in
Table 31.11 Prevalence of Thyroid Autoantibodies and Their Role in Immunopathology
TSH, thyroid-stimulating hormone.
Table 31.12 Nomenclature of Anti-TSH Receptor Antibodies
LATS Long-acting thyroid In vivo assay of stimulation Original description of serum stimulator of mouse thyroid molecule able to stimulate mouse thyroid; no longer used
TSHRAb, TRAb TSHR antibodies Competitive and functional All antibodies recognizing the TSH assays described below receptor (includes TBII (competitive), and TSI, TBI and TNI (functional) based on assay method
TBII TSHR-binding inhibitory Competitive binding assays Antibodies able to compete with immunoglobulin with TSH TSH for TSH receptor binding irrespective of biologic activity