TSI (also TSAb) TSHR-stimulating Competitive and functional Antibodies able to block TSH immunoglobulins bioassays of TSH receptor receptor binding, induce cAMP activation production and nonclassical signaling cascades
TBI (also TSBAb, TSHBAb TSHR stimulation-blocking Functional bioassays of TSH Antibodies able to block TSH antibodies receptor activation receptor binding, induce cAMP production with +/– effects on nonclassical cascades
TNI TSHR nonbinding Binding and functional assays No TSH binding, no effect on cAMP immunoglobulin levels and variable effects on nonclassical cascades
TSH, thyroid-stimulating hormone.
the diagnosis of Graves disease, the diagnosis of chronic autoimmune thyroiditis, in conjunction with TSH testing as a means to predict future hypothyroidism in subclinical hypothyroidism, and to assist in the diagnosis of autoimmune thyroiditis in euthyroid patients with goiter or nodules (348).
Another group of antibodies important in autoimmune thyroid disease bind the TSH receptor (TSHR). The TSHR belongs to the family of G-protein coupled receptors. TSHRAb are pathogenic and capable of activating (TSI) or blocking (TBI) TSH receptor functions. TBIs are detectable in two varieties: those that block TSH binding and those that block both pre-and postreceptor processes. Several investigators detected such blocking antibodies in patients with primary hypothyroidism and atrophic thyroid glands (355,356). The nomenclature and detection assay of TSH receptor antibodies are listed in Table 31.12. Anti-TSH receptor antibodies were reported in 6% to 60% of patients with hypothyroid autoimmune thyroiditis, 70% to 100% of patients with Graves disease, and 1% to 2% of the general population (357–361). Untreated Graves disease patients tested with third-generation immunometric assays are uniformly positive (362). TSHRAb are classified as binding inhibitory immunoglobulins by competitive binding assays (TBII); and in functional assays: stimulating (TSI)—according to their capacity to increase cyclic adenosine monophosphate (cAMP) production; blocking (TBI)—which possesses the capacity to reduce TSH effects; and, neutral (TNI)—with no effect on TSH binding or alteration of cAMP levels. A number of competitive and functional assays are available to determine the levels of each antibody type, which, in toto, correlate with severity of disease, extraglandular signs, risk of fetal effects, and chances for remission and recurrence. TSHRAb are used clinically to distinguish postpartum thyroiditis from Graves disease, to predict the risk of fetal and neonatal thyrotoxicosis in women with prior ablative treatment or current thionamide therapy in the setting of Graves disease, and in the diagnosis of euthyroid Graves ophthalmopathy (348). These assays will increasingly optimize individual patient testing and treatment (363).
Antibodies to the NIS are prevalent in a number of thyroid conditions. Anti-NISAbs were detected in 24% of patients with Hashimoto disease and 22% of patients with Graves disease (364). Anti-NISAbs are used experimentally (348).