Upsala J Med Sci 80: 122-126, 1975 Results of Partial Thyroidectomy for Thyrotoxicosis HENRY JOHANSSON,' FOLKE NILSSON,' A K E RIMSTEN,' ANDERS PARROW,2* GUDRUN JONSELL,3 MAGNUS MICHAELSSON" From the ' D e p a r t m e n t of Surgery, the =Department of Internal Medicine, a n d the Qepartment of Pediatrics, University H o s p i t a l , U p p s a l a , S w e d e n ABSTRACT In a retrospective study, two series of surgically treated patients with thyrotoxicosis were compared. The series dif- fered with respect to preoperative treatment and operative technique. In one series a combined preoperative treatment with an antithyroid drug and I-thyroxine was given and the recurrent nerves and parathyroid glands were routinely identified. In the other series no such operative routine was followed and iodine was given preoperatively. The compli- cation rate was low in both series. There was no postopera- tive mortality. The existing differences, although subtle, in the frequency of recurrent nerve paralysis, postoperative hypoparathyroidism or hypothyroidism, as well as recur- rent toxicosis, favoured the surgical approach with the combined preoperative treatment and a meticulous techni- que with identification of recurrent nerves and parathyroid glands. INTRODUCTION Subtotal thyroidectomy is widely employed as therapy for thyrotoxicosis. Clear indications exist for such a treatment and surgery often is thought to offer prompt and permanent relief. In addition to surgery, antithyroid drugs and radio-iodine must also be considered as sometimes superior modes of therapy. The choice of therapy is debated, however, owing to the simple fact that none is ideal, each having its own advantages and disadvantages. Immediate surgical complications are mortality and recurrent nerve injuries and as remote se- quelae, toxicosis, hypofunction of the thyroid andlor the parathyroids are considered. The com- plication rate is usually low (2, 6) though the major complication of surgery, hypothyroidism, has been observed in certain studies to have an overall inci- dence of as high as 49 % (7). Variations in complication rate certainly reflect differences in pre- and postoperative care, as well as the surgical procedure itself. Wide experience in * Present address: County Hospital, Enkoping, Sweden. Upsala J Med Sci 80 thyroid surgery and careful attention to details in operative techniques seem to lower the complica- tion rate (5, 8, 10, 1 I ) . At the University Hospital of Uppsala we have, since 1965, used standardized methods for the treatment of thyrotoxicosis, employing preopera- tive antithyroid drugs and /-thyroxine, an operative technique where meticulous care is taken in the identification of the parathyroid glands and the re- current nerves and careful follow-up examinations. I n this retrospective study, the results of the above outlined regimen are compared with those of earlier series without such an established program. The findings favour the principles for surgical treatment of thyrotoxicosis including the preopera- tive schedule, and operative techniques with routine identification of the parathyroid glands and recurrent nerves. MATERIAL Series I , o p e r a t e d b e t w e e n 1968 a n d I972 The series consisted of 108 consecutive patients who un- derwent surgery for thyrotoxicosis. The diagnosis, sex and age distribution are seen in Tables I and 11. The yearly incidence from 1968 to 1972 is presented i n Table 111. Surgery was the primary treatment in 99 cases and 9 patients were referred to surgery when medical treatment led to recurrent toxicosis. F'reoperatively the patients were treated with an anti- thyroid drug, as a rule Carbimazole (Neomercazol", British Sheerings Ltd.) supplemented with I-thyroxine (Levaxin", Nyegaard A/S). This treatment was given on an ambulatory basis and usually continued for 3 months. On the day of operation the antithyroid treatment was discontinued. Thyroxine was given postoperatively in most cases with nodular, and in some cases with diffuse, goitre, in an initial daily dose of 0.1 mg. Bilateral thyroid resection was performed for diffuse and nodular goitre and unilateral thyroid resection for toxic adenomas. In the bilateral resection, thyroid rem- nants of 4-6 g were left. Important stages in the surgical procedure were as follows: Partial thyroidectomy f u r thyrutuxicosis I23 Table I . Dirrgrzosis ctnd sex distribution of patients operrrted f b r thyrotoxicosis betkrven I968 and 1972 Table 111. Dicigno5i.Y and yearly incidence of pu- tients operrrted f o r thyrotoxicosis between 1968 and I972 M=Male, F=Female Diffuse Nodular Adenoma Diffuse Nodular Adenoma Total M F M F M F M F I968 I5 16 3 1969 16 14 2 1970 1 1 8 I 1971 4 10 0 50 49 9 I08 1972 4 1 3 10 40 9 40 2 7 21 87 1 . Transversal skin incision approximately 2 cm above the sterno-clavicular joints. 2. Separation and retraction of the sternothyroid and sternohyoid muscles in the mid-line. 3. Separate ligation of the superior thyroid artery t o avoid injury of the external laryngeal nerve. 4 . Exposure of inferior thyroid artery with ligation in continuity. 5 . Identification of recurrent nerves. 6. Identification, if possible, of parathyroid glands. Before a bilateral resection, a thorough search was made for at least one parathyroid gland. Usually at least two para- thyroid glands were identified and left at every operation. 7. Meticulous hemostasis before closing the wound, and drainage catheters (suction drainage according to Redon- Jost) for 48 hours. The vocal cords were inspected prior to the operation, at the extubation and 3 4 days after surgery. Serum calcium and phosphorous levels were determined before and after the operation. The thyroid status was followed by determinations of protein-bound iodine (PBJ) or serum-thyroxine (T4) and triiodothyronine (T,-resine test) as well a s by measuring thyroid stimulating hormone (TSH). The patients were examined 2 weeks, and 2, 6 , 18 months postoperatively and thereafter annually. The re- sults of the present study were calculated on a mean follow-up time of 30+2 months. Series 11, operated upon between 1950 and 1964 The series consisted of 114 women and is presented in Table IV. The mean age of the patients at the time of operation was 34 years ( 1 6 4 9 ) . For 2-3 weeks preopera- tively the patients were hospitalized and prepared for sur- gery with oral iodine. This treatment was started with low doses and the dosage was increased until symptoms of thyrotoxicosis disappeared or were significantly reduced. Postoperatively the dosage was successively diminished and the treatment was usually terminated on the fifth day. The operation consisted, with a few exceptions, of bilateral resection of the thyroid. Parathyroid glands and recurrent nerves were not regularly identified. In other respects the operations followed in principle the proce- dures described for series I . At the follow-up examinations all patients were investi- gated with serum determinations of cholesterol, triglycerides and TSH. PBI and basal metabolic rate (BMR) were also measured when hypothyroidism was suspected. The mean follow-up time was 12 years (6-20) after operation. Only women fertile at the time of operation were in- cluded in this material as the primary aim of the follow-up examination was to study the influence of the surgical treatment of thyrotoxicosis on fertility, pregnancies and children born thereafter. These aspects of the follow-up will be published elsewhere. In the following text the cases in series I will be referred to a s the recent series and those in series I1 as the early series. The two series were worked up with regard to postoperative bleedings (series I), vocal cord paralysis, hypoparathyroidism, hypothyroidism, and recurrent thyrotoxicosis (series I, 11). The diagnosis of hypothyroidism is based on evaluation of clinical symptoms, and lowered values of PBI, T4 or T,, sometimes in combination with an increase in TSH. RESULTS Murtalitv Table 11. Diagnosis and a g e distribution of patients operated f o r thyrotoxicusis between 1968 and 1972 Diffuse Nodular Adenoma Total Age There was no per- or postoperative mortality in either series I or series 11. -20 1 1 0 2 20-29 12 2 1 15 30-39 14 3 2 19 40-49 11 14 2 27 50-59 7 14 1 22 Postoperative bleeding 6 0 6 9 4 12 2 18 In series I, 6 patients (6 %) had postoperative bleed- 70-79 1 3 1 5 ing which required reoperation with hemostasis. In Total 50 49 9 108 no case tracheostomy was necessary. Upsaia 3 Med Sci 80 124 H . Johansson el al. Table I V . Diagnosis of female patients operated for thyrotoxicosis between 1950 and 1964 Diffuse Nodular ‘‘Undetermined’’ 82 25 7 Paralysis of recurrent nerve In series I , none of the patients (0%) had persistent paralysis. Unilateral and, within 3 months, transient paralysis occurred in 4 patients (4 %). In series 11, 3 patients (2%) suffered persistent unilateral vocal cord paralysis. Postoperative hypoparathyroidism In series I , none of the patients (0 %) had persistent hypoparathyroidism. Overt but transient hypopara- thyroidism arose in 8 patients (7%). Two of these patients required extra calcium for a few days. In series 11, one patient required vitamin D sup- plementation (DygratyP, Ferrosan, Sweden) imply- ing a persistent postoperative hypoparathyroidism of less than 1 %. Postoperative hypothyroidism In series I , most (84%) of the patients with nodular goitre and many (38 %) of those with diffuse goitre had regular administration of thyroxine post- operatively (Table V). 12 patients (11%) were characterized as hypothyroid, with one exception all having been operated for a diffuse goitre. In series 11, 50% of the patients with nodular goitre and 14% of those with diffuse goitre had regular administration of thyroxine postoperatively. 8 women (7%) were classified hypothyroid, 6 of whom were already treated with thyroxine. The values of TSH, cholesterol and triglycerides in series I1 found at the follow up are shown i n Table VI. The patients submitted to partial thyroidectomy had on the average a higher TSH- -value than the corresponding controls (normals). The values of cholesterol and triglycerides did not differ from the normals. Postoperative recurrent toxicosis In series I , 2 patients (2%) had a relapse within 12 months of surgery. Both (women, age at time of operation 18 and 27, respectively) were given anti- Vpsala J Med Sci 80 thyroid drugs for 2 years and still remain euthyroid 6 and 3 months after discontinued therapy. In series 11, 7 women ( 6 % ) had a relapse, 4 of them within 12 months. Only one was treated and cured with a thyrostatic drug, all the others were treated with radioiodine, hitherto remaining eu- thyroid. DISCUSSION The frequency of thyrotoxicosis in this region has been relatively constant for the last 20-25 years. The calculated incidence is around 30/100000, for women, 40/100000. During 1970-72 there was a di- minishing number of operations for thyrotoxicosis mainly depending o n an increased use of antithyroid drugs for the treatment of the toxic diffuse goitre. However, it has been shown that also after long- term antithyroid drug therapy only 20-35 % of the patients experienced prolonged remission ( 3 , 9 ) and an extension of the antithyroid dose did not obvi- ously reduce the number of recurrences. A still lower frequency of prolonged remission after anti- thyroid drug therapy is demonstrated in patients with Grave’s disease and enlarged goitre (9). Ap- parently long time antithyroid drug therapy can above all be expected to be successful in cases with small goitre, short duration of symptoms and with a simultaneous reduction in the size of the goitre dur- ing the treatment. These facts have in our clinic been reflected in an increased number of operations for toxic goitre during the last 2 years. In spite of certain differences in the indication, the types of operations have been identical and in both series, with very few exceptions (unilateral resection in toxic adenomas), bilateral, partial re- section was performed. However, the modes of Table V. Hypothyroidism afrer operation for thyro- toxicosis, between 1968-1972, with regard to dia- gnosis and postoperative thyroxine supplementa- tion (+) or not (-) Diffuse Nodular Adenoma n =50 n =49 n =9 + - f - + - Postoperative 3 8 0 1 0 0 hypothyroidism thyroxine supplementation Postoperative 19 31 41 8 8 1 Partial thyroidectomy f o r thyrotoxicosis 125 A routine identification of parathyroid glands is, however, no guarantee for the avoidance of post- operative hypoparathyroidism. It is not always pos- sible to find the parathyroids (12) and in attempting to identify the glands there is always the risk of damaging their vascular supply ( 1 ) . Such an injury may explain the overt but tran- sient hypoparathyroidism in the 8 patients in the recent series. We would nevertheless emphasize the usefulness of the routine identification of the parathyroids, as this technique gives a familiarity with the anatomy leading to an increased skill in the handling of more radical thyroid procedures and parathyroid surgery. The problem of the exact estimation of the fre- quency of postoperative hypothyroidism is well known and, in our two series, the liberal postopera- tive administration of thyroxine, contributes to the difficulty. The reason for our thyroid hormone treatment in nodular goitre is to avoid a recurrency of nodules and, i n diffuse goitre, to decrease the risk of the postoperative exophthalmus syndrome. However, the small daily dose, 0.1 mg I-thyroxine, cannot conceal the appearance of a real thyroid hypofunction. Postoperative hypothyroidism usually appears early, and more than 90% are revealed within 12 months (7). In the early series only 2 new hypothyroid sub- jects were discovered 12 years after thyroid sur- gery, and i n the recent series all patients characterized as hypothyrotic were observed within one year. However, our studies showing elevated TSH- levels in patients followed for an average of 12 years indicate not only an early subtle thyroid hormone deficiency ( 2 ) ; for a considerable time af- ter the operation the thyroid remnants are unable to maintain a state of euthyroidism without an exces- sive stimulation. Thus there is always the risk of a late postoperative hypothyroidism underlining the importance of life-long follow-up. Our frequencies of recurrent toxicosis are within those reported in the literature. An interesting observation is that, taken together, the percentage of hyper- and hypothyroidism postoperatively is identical-13-in our two series. These complica- tions reflect our inability to individually and exactly decide the optimal size of the thyroid remnant. The size of the remnant and the degree of lymphoid infiltration are crucial factors for a development of Table VI. Values of T S H , cholesterol and triglyce- rides in female patients operated between 1950-1964. Normal values of T S H in f e m a l e s of corresponding age are given in parentheses Mean kSD TSH (units) 12.9 3.4-49.0 Cholesterol (mg %) 252 164-384 Triglycerides (mg %) 106 38-290 (5.5) (1.2-25.0) therapy are definitely different with respect to operative techniques with routine identification of the parathyroid glands and the recurrent nerves in series I, and t o the preoperative treat- ment which is completely changed between the two series. The complication rate must be considered ac- ceptable in both series, and the differences subtle. Such a similar and low incidence of complications might be explained more by the fact that in both series our preoperative evaluations, as well as the operations, have been performed by experienced surgeons. Some observations are, however, worthy of further elucidation. None of the series suffered from postoperative mortality due to crisis, haemorrhage or tetany. This can be attributed to the adequate preoperative treatment, either with iodides or antithyroid drugs, and the advantages of modern surgery and anesthesiology. Without a doubt the preoperative treatment of today, antithyroid drugs in combina- tion with thyroxine, allows of an uncomplicated postoperative course-no abnormal increase in pulse rate o r elevation of body temperature was found. Not one crisis was observed i n the so treated patients, while in the early series one severe thyroid storm appeared, requiring intensive care. The absence of recurrent nerve paralysis in the series with routine identification of the nerves indi- cates the importance of such a procedure. Persis- tent vocal cord paralysis is reported to be rare with such an operative technique 0-0.3% (4, 12). This observation is also well confirmed in the compari- son between our series with and without routine nerve identification, 0 and 2 %, respectively. Our frequency of permanent postoperative hypoparathyroidism is extremely low and consist- ent with most recent series, in which, in the hands of experienced surgeons, the percentage ranges from 0 t o 1.4 ( 2 ) . Upsala J Med Sci 80 126 H . Johansson et al. p o s t o p e r a t i v e hypofunction. In t h e c h o i c e b e t w e e n a r e c u r r e n t toxicosis or a hypothyroid s t a t e , t h e l a t t e r is definitely p r e f e r r e d , since it is a m e n a b l e t o p r o m p t t r e a t m e n t . T h e signs of a h i t h e r t o l o w e r f r e q u e n c y of r e c u r - rent toxicosis in t h e r e c e n t series m a y b e an a d v o - cate f o r a m o r e radical r e s e c t i o n , w h i c h is certainly t h e c o n s e q u e n c e of t h e m o r e e x t e n s i v e dissection t e c h n i q u e n e e d e d for t h e routine identification of r e c u r r e n t nerves a n d parathyroid glands. REFERENCES 1 . Alveryd, A.: Parathyroid glands in thyroid surgery. Acta Chir Scand, Suppl. 389, 1968. 2. Barnes, H . V . & Gann, D. S.: Choosing thyroidectomy in hyperthyroidism. Surg Clin N Amer 54: 289, 1974. 3 . Gillquist, J., Karlberg, B., Sjodahl, R. & Tegler, L.: Preoperative treatment of hyperthyroidism. Acta Chir Scand 140: 23, 1974. 4 . Hawe, P. & Lothian, K. R.: Recurrent laryngeal nerve injury during thyroidectomy. Surg Gynec Ob- stet 110: 488, 1960. 5. Heyman, P.: Atoxic and toxic goiter. Endemiology, symptomatology and surgical treatment. Acta Chir Scand, Suppl. 289, 1962. 6 . Lamberg, B.: Skoldkortelns sjukdomar. Remedia Fennica, Helsingfors, 1969. 7 . Michie, W., Pegg, C. & Bewsher, P.: Prediction of hypothyroidism after partial thyroidectomy for thyrotoxicosis. Brit Med J I: 13, 1972. 8. Riddell, V . : Thyroidectomy. Prevention of bilateral recurrent nerve palsy. Brit J Surg57: 1 , 1970. 9 . Shizume, K., Irie, M., Nagataki, S., Matsuzaki, F., Shishiba, Y . , Suematzu, H. & Tsushima, T.: Long- term result of antithyroid drug therapy for Grave’s disease: Follow up after more than 5 years. En- docrinol Japon 17: 327, 1970. 10. Thompson, N . W., Olsen, W. R. & Hoffman, G . L.: The continuing development of the technique of thyroidectomy. Surgery 73: 913, 1973. 1 1 . Thoren, A. & Wijnbladh, H.: Operative treatment of thyrotoxicosis. Acta Endocrin 22: 224, 1956. 12. Wade, J . S . H.: The morbidity of subtotal thyroidectomy. Brit J Surg48: 25, 1960. Received February 13, 1975 Address for reprints: H . Johansson, M.D. Department of Surgery University Hospital S-750 14 Uppsala 14 Sweden Upsala J Med Sci 80