The study included a total of seventy-six patients. A large proportion of the patients underwent CCLND and LLND. Lymph nodal metastases were common in our cohort and were noted in 56(73.7%) patients. Baseline (median, range) serum Tg and TgAb were 0.27 (0.2–121) ng/dl and 166.5 (30–4000) IU/ml, respectively. The WBS was positive in 68 (89.5%) of the patients, and they received RIT. After 6 months, 84.2% of patients had a stable or fall in the TgAb range from 0 to − 98.3%, and twenty (26.3%) had ER. After a follow-up (58.74 ± 26.26 months), ER was noted in 28 patients. In the rest of the 48 (63.2%) with IR, the TgAb level ranges from 22 to 8000 IU/ml. Out of 59 patients who had fallen TgAb after RIT, 51 patients had persistent falling levels in the follow-up. A total of 11 patients underwent 18F FDG PET-CT. Five patients demonstrated metabolically active lesions, and three patients underwent cervical lymph nodes dissection. None of the patients died during follow-up. The IR group had higher baseline TgAb levels, CCLND, LLND, and central compartment lymph node metastases. The baseline TgAb ≤241.5 IU/ml has excellent sensitivity (89.3%) for predicting IR.
Long-term follow-up of DTC patients is required to detect recurrence. Serum Tg remains the cornerstone of the investigation. However, persistent TgAb may cause Tg levels to be variable. Approximately 20% of DTC patients and 10% of the general population show TgAb [15, 18]. There may be an early transient decline in TgAb from increased formation and metabolic clearance of Tg-TgAb complexes formed by a rise in Tg with surgery . Destruction of the follicles may lead to an acute increase in Tg antigen and production of TgAb. TgAb may rise or become detectable in response to thyroid surgeries, FNAC, biopsy, or RIT [15, 20,21,22,23]. After that, in the absence of a thyroid tissue mass and Tg antigen, TgAb concentrations decline over several months [24, 25]. The median half-life of TgAb after surgery for DTC is 10 weeks . We observed a transient rise in TgAb in comparison to baseline after RIT in 8 patients. All of them had a subsequent fall in the TgAb in the long-term follow-up.
Raised serum TgAb in DTC presents a unique clinical scenario and much concern to the patient and the physician. TgAb interference causes an underestimation of serum Tg when measured by IMA. However, Tg could be either under-or overestimation when measured by RIA. Minimal TgAb concentrations may interfere with Tg without being detected by a few methods. The interference is minimal when Tg (RIA) in the specimen is high and TgAb is low. However, it becomes significant when Tg is low and TgAb is high . Rising TgAb levels after initial treatment are considered as a ‘biochemical incomplete response’ [2, 26]. Several studies have demonstrated an increased risk of recurrence/persistent disease with a new appearance of TgAb or rising titers [14, 24, 27].
After surgery and RIT, the mean TgAb disappearance time is about 3 years [24, 25]. A persistently low and declining TgAb concentration after the initial surgery does not always indicate recurrence . It demonstrates the importance of long-term follow-up in this subset of patients. Our study did not find any structural recurrence in 27 (35.52%) and 51(67.05%) patients with baseline TgAb levels less than 100 and 500 IU/mL, respectively. However, recurrences were seen in 5 (31.25%) patients with TgAb> 1000 IU/mL. Kim et al. noted similar results and found that the recurrence rate was 18 and 1% for serum TgAb > 100 U/mL and TgAb ≤100 U/mL, respectively . We found that the baseline TgAb correlates with the patient’s outcome (ER: 99.61 ± 91.29 and IR: 1071.27 ± 1216.17, p = 0.001). Similar observations were seen by a few but not by all previous authors [16, 28, 29].
Our results confirm a favorable long-term outcome in patients with early normalization or significant fall in TgAb titers. Few authors have supported this finding [14,15,16]. In our study, 59 (86.8%) patients had stable or fell off (0 to − 98.3%) TgAb levels after RIT. Approximately one-third had an ER. Of these 59 patients, 51 (86.4%) patients had a persistently low TgAb level in follow-up. None of them had a rising TgAb or recurrence in follow-up. It may be due to the eradication of functional thyroid cells, benign or malignant, eliminating the antigenic stimulus [3, 25]. .Like our study, a previous study demonstrated that less than 1% of patients with 50–100% decline in TgAb after RIT had a recurrence. However, 37% of patients with rising TgAb and 19% of patients in whom the fall was less than 50% had recurrences .
In our study, only five patients (6.5%) had an anatomical recurrence in follow-up, similar to a study by Durante et al. . However, the recurrences were much lower in comparison to other studies (13.6–49%) [14, 15, 30]. This result may be due to different study populations. One of the primary inclusion criteria of our study was a negative follow-up WBS scan. This rules out the possibility of the residual normal or malignant iodine avid thyroid tissue. However, many previous studies did not have it as an inclusion criterion [10, 15, 16, 31]. It raises the possibility of minimal residual tissue in these studies that produced Tg and a persistent TgAb. It could be an associated reason for high structural recurrence in those studies. Despite high but stable TgAb levels, many patients remained asymptomatic with no evidence of structural recurrence and did not require active interventions.
Our study found that the history of lymph node dissection and lateral compartment lymph nodal metastasis were significantly associated with IR (45.8%, p = 0.01). Like our observation, Tsushima et al. also showed that N1b lymph nodes metastases and recurrence were common in patients showing < 50% fall or rising TgAb in follow-up . We found that the IR group had higher initial TgAb levels and TNM stages. However, the TNM stage was not a significant factor in multivariable regression analysis.
In a large meta-analysis consisting of 38 studies (10 648 patients), 23.8% of DTC patients had coexisting Hashimoto’s Thyroiditis (HT). It was associated with favorable clinicopathological characteristics, with no extrathyroidal extension (p = 0.002), lymph node metastasis (p = 0.04), and more prolonged recurrence-free survival (p = 0.001) . However, some studies have shown contradicting results [11,12,13, 15]. We did not evaluate the coexisting HT in our study. We utilized FDG PET-CT to assess these patients as it is considered an excellent method to detect recurrent disease .
Our study has several limitations, such as its retrospective design and the low number of patients in individual groups. Longer follow-up is needed as patients may develop recurrence at a later date. All the patients with IR did not undergo FDG PET-CT, as our center has a high FDG PET/CT threshold. We investigated only 12 patients with TgAb > 500 IU/ml. It may be a reason for the lower recurrence in our study. Future research with a large number of subjects is needed.