This study showed that factors predicting difficult thyroidectomy for GD patients differed by surgical approaches. Thyroid volume was the only factor that was associated with difficult thyroidectomy in patients who underwent OT. In patients who underwent RT, thyroid volume was associated with OP-time, while only TRAb levels significantly predicted increased EBL. In line with previous findings, preoperative thyroid hormone levels and bilateral CND were also associated with difficult thyroidectomy in the RT group [19, 20], whereas other factors, such as duration of antithyroid drug treatment, preoperative administration of potassium iodide, and smoking status, were not associated.

Because surgical techniques are dependent on operative approaches, factors predictive of difficult thyroidectomy should be analyzed separately for each approach. Previous studies have shown that factors that reduce bleeding in GD patients include preoperative iodine administration and longer antithyroid drug treatment, while thyroid volume increased risks of bleeding [1, 21,22,23]. These studies, however, evaluated GD patients who underwent conventional OT. To our knowledge, the present study is the first to compare factors predictive of difficult thyroidectomy in GD patients by operation types.

As TRAb plays a major role in the pathophysiology of GD, it is strongly associated with disease severity and prognosis [6]. No study, however, has analyzed the association of TRAb with operative outcomes, except one study which reported that TRAb did not affect intraoperative blood loss in GD patients who underwent OT [1]. Our study was in line with their findings, as TRAb did not affect EBL in OT patients. By contrast, TRAb concentration was a significant predictor of increased EBL in patients who underwent RT. This association may be due to the role of TRAb in increasing thyroid vascularity [5, 24]. Both thyroid vascularity and peak systolic velocity of the superior thyroid vessels are associated with TRAb titer [4, 25, 26], as TRAb stimulates TSH receptors which have a proangiogenic role. Because TSH receptor is expressed on human dermal microvascular endothelial cells, TSH stimulates angiogenesis by promoting capillary network formation [27]. TSH was also found to increase angiogenic markers, such as VEGF, angiopoietins, and Tie-2, in vitro [28, 29]. Therefore, it can be hypothesized that GD patients with elevated TRAb levels have hypervascular thyroid glands, increasing EBL during thyroidectomy.

TRAb increased EBL in patients who underwent RT, but not OT, suggesting that differences in operative techniques and procedures may influence EBL. The initial stage of OT consists of superior pole dissection with early ligation of the superior thyroid vessels. In BABA RT, however, thyroidectomy is performed in a caudal to cranial direction, ligating the superior thyroid vessels at last. Because higher TRAb levels are associated with increased blood flow through the superior thyroid vessels [25, 26], patients with higher TRAb would be exposed to greater vascular flow throughout the operation. Moreover, traction of the thyroid gland with engorged vessels often leads to bleeding, as the vein may be torn during handling of the thyroid gland. This is especially difficult in RT, as handling the engorged vessels with metallic robotic arms, which lack tactile sense, may lead to easier touch-bleeding. In OT, however, the use of fingers and gauzes for traction of the thyroid gland may prevent bleeding from the thyroid surface.

Immediate control of severe bleeding may take longer during RT than OT, as blood accumulation can impede the camera’s view. Moreover, it is difficult to control bleeding from the cut-end of the superior thyroid vessels during BABA RT, as the robotic arms may be unable to reach deeper into the bleeding focus. Two patients in the present study who underwent RT experienced superior thyroid vein bleeding, requiring a 2 cm mini cervical incision at the upper neck to ligate the superior thyroid vein. Both patients had high TRAb levels, 143.3 and 180.9 IU/L, respectively, and severely engorged thyroid vessels.

The present study had several limitations. First, EBL is a crude estimate of intraoperative blood loss, resulting in possible information bias. Because this was a preliminary retrospective study, further prospective studies are needed using specific determinations of blood loss to assess its association with TRAb. Second, selection bias could not be avoided, as this study was retrospective in design and included a small number of study subjects from a single center, with all undergoing surgery by a single surgeon. Third, the results do not represent all types of robotic approaches, as all RT patients in this study underwent BABA RT. Because other types of RT have different operative procedures than BABA RT, further studies are needed to identify individual factors for difficult thyroidectomy in each approach. Fourth, TRAb was not measured at the same time relative to surgery in all patients, with measurements obtained within 6 months prior to surgery used, leading to possible information bias. Finally, while autoantibodies can both stimulate and block TSH receptors, the immunoassays and radioassays used in this study could not differentiate the activities of the TRAb [30]. Cell-based bioassays are appropriate for this differentiation, but these assays are not readily available in clinical practice [30]. However, since most GD patients underwent thyroidectomy due to uncontrolled disease caused by overstimulation by TRAb, using clinical TRAb results as a guide to predict increased EBL may be feasible.

In conclusion, caution should be exercised in performing BABA RT on GD patients with high level of TRAb, regardless of thyroid size. Preoperative preparation of intravascular lines and suction devices, and readiness to make additional incisions may be helpful in performing BABA RT on GD patients with high TRAb. Alternatively, conventional OT may be more feasible in these patients. Other factors, such as bilateral CND, high thyroid hormone levels, and high thyroid volume have been associated with longer OP-time or higher EBL, as well. Prospective studies in large numbers of patients are needed to support these findings.