7771 Surveillance Role in Differentiated Thyroid Cancer Through Ultrasensitive Thyroglobulin IRMA with High Negative Prediction Value

Abstract Disclosure: J. Jang: None. H. Kim: None. S. Ha: None. K. Jung: None. G. Jung: None. S. Cho: None. D. Park: None. G. Cheon: None. Y. Park: None. TSH-stimulated serum thyroglobulin (s-Tg) is a well-established marker for monitoring differentiated thyroid cancer (DTC) following remnant ablation therapy. The 2nd-generation immunoradiometric assay for Tg (ultrasensitive Tg, uTg) was developed to detect Tg with higher sensitivity compared with the 1st generation (conventional Tg, cTg). This study aimed to compare efficacy of both methods, cTg and uTg, to determine whether unstimulated Tg (us-Tg) could predict s-Tg levels. Paired serum samples were collected from 274 DTC patients before (us-Tg) and after (s-Tg) TSH stimulation for 1st radioiodine therapy after surgery (1st Tg) or both 1st therapy and 2nd therapy/diagnostic test (1st and 2nd Tg, respectively). Both cTg (Dynotest Tg-plus, BRAHMS Gmbh, Germany, LOD 0.1 ng/mL and functional sensitivity (FS) 0.2 ng/mL) and uTg (RIAKEY, Shinjin Medics, South Korea; LOD 0.01 ng/mL and FS 0.06 ng/mL) were measured. For analysis, samples with inadequate TSH stimulation (<30 μIU/mL) or with anti-thyroglobulin antibody levels > 60 U/mL were excluded. Ultimately, the included samples consisted of 296 for us-Tg and 352 for s-Tg.. Among these, paired samples for us-Tg and s-Tg were available in 260 cases (189 for 1st Tg and 71 for 2nd Tg). Comparing all Tg values, cTg and uTg levels had a correlation (Intraclass correlation coefficient r=0.752, P < 0.001), with no significant difference between us-Tg (r=0.803, P < 0.001) and s-Tg (r= 0.752, P < 0.001). The optimal cut-off level for predicting s-cTg at 1 ng/mL was 0.12 ng/mL in uTg or 0.16 ng/mL in cTg tests using AUC-ROC curve analysis. Considering the FS for cTg, diagnostic performance was assessed with a cut-off level of 0.2 ng/mL for cTg and 0.16 ng/mL for uTg. For s-cTg positivity as ≥ 1 ng/mL, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of uTg were 72.1%, 59.8%. 52.0%, and 78.0%, respectively, while for cTg, they were 33.3%, 95.3%, 78.4%, and 73.9%, respectively. Similar trends were observed for s-cTg ≥ 2 ng/mL (69.0%, 71.4%, 35.0%, and 91.2% for uTg, respectively; 49.0%, 93.8%, 64.9%, and 88.7% for cTg, respectively). In essence, uTg demonstrated higher sensitivity than cTg, while having lower specificity and PPV, with a similar NPV. Of the 71 patients with paired 2nd Tg levels, 7 (9.8%) had biochemical disease (BCD) by s-cTg (1 ng/mL), whereas only 1 (1.4%) showed BCD using us-cTg ≥ 0.2 ng/mL. Conversely, 40 (56.0%) were classified as BCD using us-uTg ≥ 0.16 ng/mL. During the 6.48 years of follow-up, 4 patients developed structural recurrence; all had positive us-Tg levels with uTg tests, while only 1 patient demonstrated positivity with cTg tests. Although, the ultrasensitive Tg is sensitive in predicting positive stimulated Tg and recurrence, the specificity is very low resulting high frequency of BCD cases without clinical significance. Therefore, the clinical utility of uTg appears to be limited. Presentation: 6/2/2024