THYROID-HORMONE AUTOANTIBODIES ELICITED BY DIAGNOSTIC FINE-NEEDLE BIOPSY

Based on the knowledge that diagnostic fine needle biopsy of the thyro id (FNAB) results in a prompt increase in circulating thyroglobulin (T g), we evaluated whether Tg is indeed the postulated antigen for circu lating antibodies against thyroid hormones (THAb). Preliminarily, we v erified that FNAB causes the release into the bloodstream of iodinated , heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawing s sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the follo wing parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb ; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most oft en peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to p ositive, and only 12% of those initially positive had an increase in t he levels of TgAb. 3) THAb were detected in 0 of 400 patients before F NAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goi ter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were Tg Ab negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the I gM class in all 9 (6 against T-3 and 3 against T-4), and were accompan ied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T-3 and 1 against T-4) in 3 cases. In a fourth case, IgM-T-3 were followed by a long-lasting synthesis of IgG-T-3 (i. e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remaine d TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetec table TgAb, THAb were of the IgM class only. 6) In the HT group, 2 ris k factors for the development of post-FNAB THAb appeared to be pre-FNA B TgAb levels below 400 U/mL that did not increase after FNAB and Tg r eleased from a colloid nodule. We conclude that Tg release from the th yroid is sufficient to elicit THAb synthesis. In patients with autoimm une thyroid disease (HT), this synthesis occurs with a frequency 10-fo ld higher than that in patients with nonautoimmune thyroid diseases (2 1% vs. 2%). However, in only a fraction of patients with autoimmune di sease, who need to be TgAb positive by a sensitive assay, the primary immune response (IgM) is followed by a secondary one (IgG). As, once p resent, this secondary response is long lasting in only a minority of our patients, we think that this could contribute to the rarity of nat urally occurring THAb.