Total Thyroidectomy as a Method of Choice in the Treatment of Graves' Disease

Analysis of 1432 Patients

Toplica Bojic; Ivan Paunovic; Aleksandar Diklic; Vladan Zivaljevic; Goran Zoric; Nevena Kalezic; Vera Sabljak; Nikola Slijepcevic; Katarina Tausanovic; Nebojsa Djordjevic; Dragana Budjevac; Lidija Djordjevic; Aleksandar Karanikolic


BMC Surg. 2015;15(39) 

In This Article

Results and Discussion

Table 1 shows the indications for surgical treatment of GD, which included thyromegaly, confirmed nodule >1 cm in diameter, ophthalmopathy and resistance to antithyroid drug therapy. The indication for surgery in the majority of 831 (65%) patients operated for GD was thyromegaly, while a smaller number, 143 patients (10%), were related to ophthalmopathy and an ultrasound diagnosed nodule >1 cm.

Table 2 shows the distribution of patients according to the type of operation. During the studied 15-year period, in 974 patients (68%) the operation of choice for GD was TT, while D was the operation of choice in only 221 (15.4%) patients. STT was performed only in the first half of the studied period. With the development of surgical technique this procedure was abandoned. At our institution, the remnant of tissue which is normally left after STT is approximately 2 g on each side, while after D its approximately 3 g on one side only.

Table 3 shows the incidence of thyroid cancer in patients operated for GD. In 145 patients (10.2%) with GD, definitive pathohistological examination revealed thyroid cancer. Carcinomas of less than 1 cm (microcarcinomas) were represented in 129 patients (89.8%), while greater than 1 cm were present in 17 patients (1.2%). In the remaining 1286 patients (89.8%) we did not observe the existence of cancer.

The incidence of complications in relation to the type of operation is shown in Table 4. Postoperative hypoparathyroidism, was most frequent in patients who underwent TT, 31 (3.2%), whereas for patients who had D it was present in 8 (3.6%), and 3 (1.3%) for patients with STT.

Postoperative unilateral recurrent nerve paralysis was reported in 9 (0.9%) patients who had TT, 1 (0.5%) who had D, and 2 (0.8%) who underwent STT. Bilateral vocal cord paralysis was not noted.

In patients who underwent TT postoperative bleeding occurred in 10 (1%), with D in 1 (0.5%) and in the group with STT in 2 (0.8%).

The incidence of complications was not statistically significantly different in relation to the type of surgical intervention (Fisher test, p > 0.05).

Frequency of associated complications is still lower than the frequency of non associated complications: permanent hypoparathyroidism with bleeding 5 (0.5%) in the TT group; 2 (0.9%) in the D group and 1 (0.4%) in the STT group. Post-operative unilateral recurrent nerve paralysis with bleeding was reported in 3 (0.3%) in TT group; 1 (0.5%) in the D group, and without associated complications in the STT group. Permanent hypoparathyroidism with postoperative unilateral recurrent nerve paralysis was present in 2 (0.2%) patients in the TT group and without these associated complications in the other groups (Table 4).

The incidence of associated complications are also not statistically significantly different in relation to the type of surgery (Fisher test, p > 0.05).

By the end of the twentieth century, STT and D were the most commonly applied operation in the surgical treatment of GD on the grounds that the complications (postoperative hypoparathyroidism and recurrent laryngeal nerve palsy) were less frequent compared to TT. At the beginning of the twenty-first century, it became clear that STT and D were linked to a high risk of relapse of GD[9,10] and surgeons in specialized centres started to use TT as the operation of choice in the treatment of GD. In addition to that, the fact that TT removes the target organ for GD leads to the elimination of the autoimmune stimulus and improvement of the ophthalmopathy in these patients.[11] Also, TT permanently removes the risk of cancer in patients already having it, as TT represents an adequate surgical intervention both for GD and for carcinoma of the thyroid gland.[9]

The series in our study represent uniform patient data obtained from a single institution and operated by four surgeons. According to available literature, our series are the largest single series of patients operated for Graves' disease in a single institution. A larger number of patients was only shown in a study of Palit et al., but this study is a meta–analysis of 35 clinical studies and included 7241 patients.[2]

Our study showed that TT is a safe and effective method of treating GD and has low complication rates.

Even when the initial treatment is surgery, the choice of the primary treatment option depends on the adequate cooperation of an endocrinologist, a specialist in nuclear medicine and an endocrine surgeon.[12] The choice of an adequate operation for GD is still the subject of debate,[13] although after the year 2000, TT has become the treatment of choice for GD in many highly specialized centres in the world.[9,14,15]

Of the total number (1432) of treated patients with GD significantly more were women 1211 (84.6%), while there were 221 men (15.4%), which roughly corresponds to the ratio 6 to 1. Analyzing our series of patients we did not find any significant differences in relation to gender in comparison to other authors.[13,16] The average age of the patients was 34.8 years (21 to 76) which is slightly higher than data available in literature.[2,16]

In the US, the number of patients with GD that are surgically treated is small. According to the data of the American Thyroid Association, surgery is, in the US, a method of treatment in only 2% of patients with GD and only in 7% of patients with GD and thyromegaly.[17]

Total or near total thyroidectomy is recommended for patients with ongoing thyroid cancer, those who refuse radio-ablation as a therapeutic procedure, or have a life threatening reaction to antithyroid drugs such as vasculitis, agranulocytosis and liver failure.[9]

Total thyroidectomy is recommended to patients with Graves' ophthalmopathy to eliminate the autoimmune stimulus from the orbital antigens.[11,18]

Due to a relatively low rate of complications for TT, compared to less extensive procedures, many authors recommended TT as the treatment of choice for GD.[16,19–21]

In our study the most common indication for surgery was thyromegaly (65%), followed by ophthalmopathy and ultrasound diagnosed thyroid nodule >1 cm (10%).

In the study of Geeta et al., in a series of 103 patients operated for GD, indications for surgery were 18% for thyromegaly, 26% for identified thyroid nodule and 20% for ophthalmopathy.[14]

In our study, thyroid cancer was found, on definitive histopathological examination, in 146 patients (10.2%) with GD. Carcinomas smaller than 1 cm, or microcarcinomas, were present in 129 patients (9%), while greater than 1 cm were present in 17 patients (1.2%).

The incidence of thyroid cancer in GD by other authors is from 0% to 21%.[22,23] In our study it was 10.2%, but on a much larger number of patients than in the studies of the cited authors Gabriele et al. (64)[22] and Calo et al. (71).[23] In the study by Geeta et al., thyroid cancer was found in about 8% of studied patients, in a series of 103 patients operated for GD.[14]

In the study by Mittendorf and McHenry in a series of 32 patients with GD, carcinoma was found in 6% of operated patients,[21] and the study of Pellegriti et al. found 4.7% of apparent clinically manifest carcinoma and 3.3% of occult thyroid carcinoma in a series of 450 patients with GD.[24]

In our study, postoperative permanent hypoparathyroidism, was most frequent in patients who underwent TT (3.2%), whereas it was lowest (1.3%) among patients who underwent STT. Postoperative unilateral recurrent nerve paralysis was most common in patients who had TT (0.9%) and STT (0.8%), while it was much rarer in patients who had D (0.5%). Postoperative bleeding was more frequent in patients with TT (1%), than in patients with D (0.5%) or STT (0.8%).

In the study of Palit et al., (meta-analysis of 35 clinical studies with a total of 7241 patients) it was reported that there were no significant differences for any violation of the recurrent nerve (0.7% of STT compared to 0.9% for the TT) or for postoperative permanent hypoparathyroidism (1.0% for the STT compared to 0.9% for the TT).[2]

In the study of Wilhelm et al., in a series of 136 patients, they recorded hematoma in the neck in only one patient (0.8%);[10] while the study of Jenkinks and Backer states that TT performed by an experienced surgeon has a rate of temporary recurrent nerve palsy of less than 1%, while postoperative bleeding ranges between 0.3% and 0.7%.[25]

The incidence of complications in patients operated for GD in our series is low and is similar to the frequency of complications in other specialized centres in the world. About 65% of patients in the study of Mittendorf and McHenry have developed transient postoperative hypoparathyroidism[21] and the extent of surgical intervention alone is taken as an important influential factor of transient and permanent postoperative hypoparathyroidism.[26]

The low incidence of complications in our study is the reason why we advocate TT in the surgical treatment of GD.

In relation to the type of surgery we did not find any significant differences in any of the two groups of complications.

The high incidence of postoperative permanent hypoparathyroidism, and associated complications (hypoparathyroidism with bleeding), in patients who underwent D is not a surprise. Although D operations are less radical than TT, in recent years, D is performed as a coerced surgical procedure for those patients in which we did not reliably identify the recurrent nerve and/or preserved the vascularisation of the parathyroid glands on the first side of the operated thyroid gland.