World J. Surg. 29, 921924 (2005) DOI: 10.

1007/s00268-005-7767-3

Comparison of Surgical Techniques for Treatment of Benign Toxic Multinodular Goiter

Orhan Alimoglu, M.D.,1,4 Murat Akdag, M.D.,1 Mustafa Sahin, M.D.,1 Cagatay Korkut, M.D.,2 Ismail Okan, M.D.,1 Neslihan Kurtulmus, M.D.3
1 2 3

First Department of Surgery, Vakif Gureba Training Hospital, Istanbul, 34080, Turkey Department of General Surgery, Istanbul Medical Faculty, University of Istanbul, Istanbul, 34080, Turkey Department of Internal Medicine, Vakif Gureba Training Hospital, Istanbul, 34080, Turkey 4 Orhan Alimoglu, Mevlana Mah. Hekim Suyu Cad., Dostluk Sitesi D 1 Blok D:13, Istanbul, Kucukkoy, 34080, Turkey Published Online: June 16, 2005 Abstract. Controversy remains regarding the best surgical approach for toxic multinodular goiter (MNG). The aim of this study was to evaluate the results of various thyroid operations for managing toxic MNG. A group of 100 patients with toxic MNG were divided into three groups and managed with total thyroidectomy (TT; group I, n-17), near-total thyroidectomy (NTT; group II, n = 48), or bilateral subtotal thyroidectomy (BST; group III, n = 35). Patients were compared with regard to age, gender, surgical operations, complications, thyroid hormone status, duration of hospitalization, and the reoperation rate for incidentally found thyroid carcinomas. There were 14 men (14%) and 86 women (86 %) with a mean age of 47.03 13.56 years (range 1977 years). After the operation two patients had a hematoma, and one patient had a seroma. Four patients had unilateral vocal cord paralysis, and one had permanent paralysis. Moreover, 18 patients had transient and 2 patients permanent hypocalcemia. There was no signicant difference between the groups regarding complications (p < 0.05). Permanent hypothyroidism was achieved in all patients in group I and 44 patients (92 %) in group II, whereas in group III only 10 (29%) patients had hypothyroidism. Conversely, hyperthyroidism, both subclinical and clinical, was noted only in group III (12 patients, 34 %) during follow-up. We think that TT and NTT are safe, effective approaches in the treatment of toxic MNG, preventing recurrence of thyrotoxicosis and reoperation for incidentally found thyroid cancers. The complication rates for TT and NTT were similar to that for BST. Hence these operation should be considered for patients referred for surgical treatment of toxic MNG.

Moreover, discussions on the extent of surgery to be performed for toxic MNG are still ongoing. Subtotal thyroidectomy has long been advocated as the standard treatment because of the possibility of avoiding thyroxine therapy as well as the assumed lower risk of complications compared to those seen after total thyroidectomy. However, the proponents of total thyroidectomy argue that to leave behind a remnant of thyroid tissue sets the scene for recurrent goiter and the potential need for reoperation with its attendant risks. They also state that the high morbidity associated with total thyroidectomy is presumptive and can be avoided by employing appropriate surgical technique. Therefore, if the risk of complications from total thyroidectomy is not high, the procedure offers signicant advantages in the surgical management of toxic MNG [814]. The purpose of the present study, then, was to evaluate the results of various thyroid operations in the management of toxic MNG. Methods Patients Between January 2000 and December 2003 a total of 100 consecutive patients with toxic MNG underwent thyroid surgery at the 1st Department of Surgery, Vakif Gureba Training Hospital, Istanbul, Turkey. The Patients data were collected prospectively, and the study was designed as a nonrandom, prospective type. Any patient with preoperative or perioperative suspicion of malignancy was excluded. The diagnosis of toxic MNG was established by history, clinical examination, biochemical investigations [sensitive thyroid stimulating hormone (sTSH), free triiodothyronine (fT3) and free thyroxine 4 (fT4)], ultrasonography, and the radioactive iodine-131 uptake test (scintigraphy). Fineneedle aspiration biopsy was employed on the dominant nodule(s). All patients were examined with indirect laryngoscopy before surgery. Antithyroid drugs (methimazole or propylthiouracil) were used to achieve euthyroid status preoperatively. b-Receptor blockers were administered when the clinical indication was present.

Toxic multinodular goiter (MNG) is thyroid gland enlargement that has at least two autonomously functioning thyroid nodules secreting excessive amounts of thyroid hormone, which produce the classic signs and symptoms of hyperthyroidism. The exact cause of toxic MNG is still obscure. Typical signs and symptoms of hyperthyroidism together with the laboratory data and imaging ndings are usually enough to establish the diagnosis [1, 2]. Although a variety of therapeutic modalities, including surgery, radioiodine, antithyroid medication, and percutaneous ethanol administration, are currently in use, Consensus on an optimal treatment, however, is still not present [37].
Correspondence to: Orhan Alimoglu, M.D., e-mail: oalimoglu@yahoo. com

922 Table 1. Clinical proles of the patients. Parameter Sex (M/F) Age Size of the dominant nodule (mm) Hospitalization time after surgery (median days and range) *Groups I and III are significantly different (p = 0.024). **Groups I and II are significantly different (p = 0.029). Group I (n = 17) 2/15 54.6 12.2* 35.9 13.1** 4 (117)

World J. Surg. Vol. 29, No. 7, July 2005

Group II (n = 48) 8/40 46.4 13.1 25.3 16.3 3 (115)

Group III (n = 35) 4/31 47.0 13.5 26.2 15.2 3 (115)

Table 2. Distribution of complications in various thyroidectomy operations. Complication Transient vocal cord paralysis Permanent vocal cord paralysis Transient hypocalcemia Permanent hypocalcemia Postoperative hemorrhage Postoperative seroma Wound infection Postoperative hyperthyroidism Group I (n = 17) 1 (5.88%) 6 (35.29%)** 1 (5.88%) Group II (n = 48) 2 (4.16%) 1 (2.08%) 7 (15.58%) 1 (2.08%) 2 1 (1.00%) Group III (n = 35) 1 (2.85%) 5 (14.28%) 12 (34.00%)*

*Group III is significantly different (p = 0.001). **p = 0.076.

Patients were sorted into three groups during the operation according to the preference of the attending surgeon: group I, total thyroidectomy (TT) (complete removal of thyroid gland); group II, near-total thyroidectomy (NTT) (total removal of the lobe with the dominant nodule and removal of the opposite side leaving < 2 g of thyroid tissue); group III, bilateral subtotal thyroidectomy (BST) (removal of the gland leaving 5 g of thyroid tissue on each side). TT and NTT were performed by capsular dissection, and the recurrent laryngeal nerve (RLN) was sought during localization of the ligament of Berry. Vocal cords were reassessed by indirect laryngoscopy 2 days after surgery. Permanent vocal cord paralysis due to RLN palsy was dened as ongoing immobility of the vocal cords 6 months after surgery. Blood samples were obtained from the patients for determining the serum calcium levels after 24 hours. Calcium gluconate was infused in patients with hypocalcemia (serum calcium level < 7 mg/ml), and thereafter calcium carbonate was continued per os. On demand, calcitriol 0.25 or 0.5 lg/day was given. If the patient required a calcium supplement to maintain a normal serum calcium level for 6 months or longer, it was considered permanent hypocalcemia. Thyroid functions were evaluated with fT3, fT4, and TSH levels checked at 1, 3, 6, and 12 months after the operation. The groups were compared with regard to age, sex, surgical method, complications, hypothyroidism, hyperthyroidism, duration of hospitalization, and the reoperation rate for the thyroid carcinomas found incidentally.

limit was predetermined at an a level of 0.05. A p value of < 0.05 was considered signicant.

Results There were 14 men (14%) and 86 women (86%) with a mean SD age of 47.03 13.56 years (range 1977 years). The mean postoperative length of hospitalization was 3.86 2.92 days. The mean follow-up was 24 months (654 months). The patients had symptoms 2 to 48 months before surgical management. The mean size of the dominant nodule was 27.35 5.78 mm. Altogether, 54 patients had the dominant nodule on the right lobe of thyroid and 46 patients on the left lobe. The number of patients distributed in the groups were 17 (17%), 48 (48%), and 35 (35%) for groups I, II, and III, respectively. The clinical prole of the patients distributed thorough the groups is shown in Table 1. Serum fT3 and fT4 levels were elevated, whereas serum TSH was depressed in all patients. All of the patients complained of clinical thyrotoxic symptoms, and clinical signs of toxicity were present in all of them. Antithyroid medication before surgery was administered to all patients, and thryroid ultrasonography and scintigraphy were performed in all of them. Vocal cord paralysis was not detected in patients preoperatively. Two patients had a hematoma, and one patient had a seroma. Postoperatively, two patients in group II and one patient each from groups I and III developed transient unilateral vocal cord paralysis. Permanent paralysis was seen in only one patient from group II. Similarly, six patients from group I, seven patients from II, and ve patients from group III developed transient hypocalcemia. One patient from each of groups I and II had permanent hypocalcemia. With regard to complications, their distribution throughout the groups did not differ signicantly (p > 0.05) (Table 2). Permanent hypothyroidism developed in all patients of group I and 44 (92%) patients of group II. There was no hyperthyroidism in group I or II. However, in group III, 4 (11%) patients had elevated

Statistical Analysis Statistical analysis between groups was performed using Students t-tests. Variables with heterogeneous variances were analyzed by Kruskal-Wallis tests. Differences involving categoric variables were tested for signicance with Yates corrected chi-squared test or, when appropriate, with Fishers exact test. The condence

Alimoglu et al.: Treatment of MNG Table 3. Changes in surgical management for toxic multinodular goiter throughout 4 years. Year 2000 2001 2002 2003 Total Group I 0 0 2 15 17 Group II 2 5 17 24 48 Group III 7 7 12 9 35 Total 9 12 31 48 100

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thyroid hormone levels with a suppressed TSH value (clinical hyperthyroidism), 8 (23%) patients had normal thyroid hormone levels with suppressed sTSH values (subclinical hyperthyroidism), 13 (37%) had euthyroidism and 10 (29%) with hypothyroidism. Histopathologic examination of resected thyroid samples revealed that incidentally found papillary carcinoma was detected in one patient each in group I and III and in two patients of group II. Completion thyroidectomy was performed on the patient in group III. In our clinic in recent years, the rates of TT and NTT increased (p < 0.05) (Table 3). The hospitalization time did not differ between the groups (p > 0.05) (Table 1). Discussion Although there is no argument that toxic MNG must be treated, the choice of management has long been a matter of controversy. Antithyroid drugs, radioiodine, and surgery are traditional treatment options for toxic MNG. The preferred modality in a given patient varies with the age of the patient, the level of hyperthyroidism, the size of the nodule or goiter, and the patients preference [2, 3, 15, 16]. Antithyroid drugs are used as rst-line treatment with the intent of producing a remission after a certain period of time. However, hyperthyroidism recurs after cessation of therapy in more than 95% of cases [17]. These agents are best used to render the patient euthyroid before more denitive treatment is undertaken. Another option is radioiodine, which is a safe, effective treatment for toxic MNG. However, the expected effect is delayed and a large, eventually compressive goiter is left in place [18]. Surgery is indicated in patients desiring or requiring rapidly efcient, denitive treatment. It is also the preferred treatment of choice for patients with suspicion of cancer, a massive goiter, symptoms of local compression, nodules with low radioiodine uptake, urgent need for control of disease, and severe hyperthyroidism [15, 1923]. The extent of thyroidectomy in the management of the disease is still debatable. The aims of surgical management for toxic MNG are to eliminate the hyperthyroidism, minimize the need to reoperate for carcinoma, and avoid the recurrence of goiterwith low complication rates. The treatment of patients with toxic MNG includes TT, NTT, and BST [18]. In the present study, the only criterion for the type of surgery chosen was the surgeons preference. Total thyroidectomy should be regarded as a logical surgical procedure for the treatment of toxic MNG. Subtotal thyroidectomy leaves behind presumably abnormal thyroid tissue and exposes the patient to the potential risks of either persistent symptoms or recurrent disease in the future. Persistent symptoms occur not infrequently after a subtotal procedure, as the dissection involved may leave the posteriorly placed nodules behind the esophagus (or between the trachea and the esophagus), and these

nodules could be responsible for many of the patients symptoms [11]. This may lead to insufcient management of toxic MNG. Indeed, in our study although there was no hyperthyroidism recurrence in the TT and NTT groups, the subtotal thyroidectomy group contained four patients (11%) with clinical hyperthyroidism and eight patients (23%) with subclinical hyperthyroidism. Our rate of postoperative hyperthyroidism was higher than in the literature. The reason for this discrepancy may lie in our denition of BST. Many previous reports recommended a maximum of 5 g of thyroid tissue left behind overall, half of what was left in our study. Therefore, the amount of thyroid tissue left in place after the operation may be proportional to the incidence of postoperative hyperthyroidism. Both groups of patients (those with subclinical or clinical hyperthyroidism) should be treated with antithyroid medication. In the literature, with long-term follow-up recurrent goiter was reported after subtotal thyroidectomy in as many as 25% to 40% of cases. The selection of BST for benign thyroid disorders is further challenged by the possibility of incidentally found malignancy in resected specimens. We noted thyroid malignancy in four patients (4%). The patient who belongs to the BST group underwent completion thyroidectomy. As in our case, BST carries the risk of leading to a second thyroid surgery due to either the high rate of recurrence or a detected malignancy in the resected specimen. Because of brosis, new dissection of the posterolateral face of the thyroid gland can cause a high incidence of unilateral RLN paralysis (up to 10%) and of permanent hypoparathyroidism (up to 20%), increasing the number of complications as much as 20-fold [3134]. Near-total throidectomy, an alternative to TT, can be considered an intermediate procedure between TT and BST. NTT can be performed to treat toxic MNG, with low rates of postoperative complications. Although there is no difference in the incidences of transient and permanent RLN paralysis and permanent hypocalcemia between TT and NTT, it has been reported that TT has a higher rate of transient hypocalcemia than NTT [15]. The only real argument against TT is the potential for an increased risk of complications. However, there is good evidence to show that, with increasing experience and the use of appropriate surgical technique (the capsular dissection method), TT and BST have complication rates comparable to those of total and subtotal thyroidectomy [2729, 35]. Although the only cases of permanent vocal cord paralysis was seen in the NTT group in this study the incidence of neither transient nor permanent paralysis showed a statistical difference. Likewise, the incidence of hypoparathyroidism did not differ among groups. Although the incidence of transient hypocalcemia was higher in the TT group and permanent hypocalcemia was not detected in the BST group, the difference was not statistically signicant.

Conclusions In recent years, TT has emerged as a surgical option to treat patients with benign thyroid disorders [9, 29, 3537]. Our clinic has also recently adopted the total and near-total procedures for patients with toxic MNG, as can be seen in Table 3. We believe that TT and NTT are safe, effective approaches for preventing recurrence of thyrotoxicosis, eliminating probable malignancies on the remnant thyroid tissues, and avoiding completion thy-

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