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Indian Journal of Surgery
Medknow Publications on behalf of Association of Surgeons of India
ISSN: 0972-2068
Vol. 64, Num. 6, 2002, pp. 506-510

Indian Journal of Surgery, Vol. 64, No. 6, Nov - Dec. 2002, pp. 506-510

Total Versus Subtotal Thyroidectomy in Grave's Disease: A Retrospective Analysis

N. Dorairajan, M. Ramkumar, Korah T. Kuruvila, Scott Arockia Singh, Maniselvi, Preetha Muthayya

Madras Medical College and Research Institute, Chennai - 600 003
Address for correspondence: Prof. N. Dorairajan , Akshaya , F 94, Anna Nagar East , Chennai - 600 102. E-mail: ndr@dr.com

Paper received: June 2001
Paper accepted: December 2001

Code Number: is02006

ABSTRACT

Grave's disease is a relatively common condition occurring in 0.4% of the Indian Population. The treatment options for Grave's disease are radioactive iodine ablation, administration of anti-thyroid drugs and surgery. Both the non-surgical modalities require long-term continued patient follow up, which is not feasible in the Indian setup. Also, surgery is a rapid, consistent and effective method of making the patient euthyroid.15 Surgical treatment involves the removal of the thyroid gland either in entirety or a part of it. These procedures aim at reducing the thyroid gland volume to levels well below the "critical mass", which is believed to be the ideal volume of remnant producing no recurrence of hyperthyroidism and minimal hypothyroidism. The ideal surgical modality is still a matter of debate. This is a retrospective study that compares the advantages and disadvantages of total and subtotal thyroidectomy and comes to a conclusion that the former is a better treatment option particularly in the presence of exophthalmos.

Key words: Grave's disease, Subtotal thyroidectomy, Total thyroidectomy, Critical mass

INTRODUCTION

Grave's disease (immunogenic primary hyperthyroidism) arises most commonly in females less than 30 years of age with clinical features that are well characterised, long established and usually easily recognized. While symptoms such as irritability, sleeplessness, excess sweating and menstrual disturbance arise due to any cause resulting in an excess circulating thyroid hormone, eye signs such as exophthalmos, lid lag and ophthalmoplegia are unique to Grave's disease. There is evidence that this autoimmune process of exophthalmos is related to a cross reacting antibody between eye muscles, retro orbital fatty tissues and thyroidal microsomes. Although these eye changes usually remit spontaneously, they sometimes persist even after treatment.

This retrospective study was undertaken to compare the incidence of complications (viz. recurrent laryngeal nerve (RLN) palsy, hypoparathyroidism, hypothyroidism and recurrent hyperthyroidism) and regression of symptoms (viz. thyroid-associated ophthalmopathy, thyroid hormone levels and anti-thyroid antibody titres) following total and subtotal thyroidectomy and to identify as to which may be the better option in the management of Grave's disease as recent data suggest that total thyroidectomy is better suited in endemic areas.1

MATERIAL AND METHODS

A review analysis of the surgeries done for Grave's disease by the senior author (ND) at Madras Medical College and General Hospital during a period of 5 years (1994-1999) and the complication rates for the two modalities of surgeries performed i.e. subtotal and total thyroidectomy were reviewed through the years from 1994 to 1996. All patients with primary goitre, clinical and biochemical features of hyperthyroidism with uniform uptake of isotope on a radioactive iodide scan were included in the study. Patients with coexistent medical illness including diabetes mellitus, hypertension, cardiovascular illness and all conditions resulting in increased anesthetic risk were excluded.

Patients were matched according to age groups and socio economic status. All patients were operated on after having been rendered euthyroid with neomercazole. In our study total thyroidectomy was defined as removal of all visible thyroid tissue with autotransplantation of parathyroids in the sternomastoid. Subtotal thyroidectomy was defined as excision with a remnant of 6 - 8 gram of thyroid tissue. Total thyroidectomy was the only mode of surgery performed for Grave's Disease from 1997 onwards till date. Serum calcium levels were routinely measured postoperatively and during follow up every third month upto the end of the first year. Serum T3 and T4 levels as well as anti thyroid antibody levels were also measured. In patients presenting with exophthalmos, the clinical status regarding the regression or progression was measured using an opthalmometer. In a few selected patients with ophthalmopathy [based on avaliability of the test in our set up] serum anti microsomal antibodies were measured. The following data were recorded. (Tables 1, 2, 3 and 4)

Table 5

RESULTS

Graph 1, 2 and 3

A total of 480 cases were studied from 1994-1999. One hundred and seventy-five cases underwent total thyroidectomy (Group A) while 305 underwent subtotal thyroidectomy (Group B). The complications in the immediate postoperative period were transient RLN palsy, hypoparathyroidism and haematoma formation.

Four cases in group A (2.2%) and 6 cases in Group B (1.9%) developed transient RLN palsy (P Value <0.5). While 9 cases in Group A (5.1%) and 12 cases in Group B (3.9%) developed transient hypoparathyroidism (P Value <0.4), both the above complication rates were statistically insignificant showing that there was not much difference between these two surgical modalities as far as immediate complications were concerned.

The delayed complications (noted at 3 and 6 months follow-up) were permanent RLN palsy, hypoparathyroidism , hypothyroidism and recurrent hyperthyroidism.

Two patients in Group A and 3 in Group B (0.98%) showed permanent RLN palsy (P Value <0.5). Permanent hypoparathyroidism was noted in 5 patients in Group A (2.8%) and 8 patients (2.6%) in Group B (P Value <0.39). While recurrent hyperthyroidism was seen in 69 % of Group B patients, patients in Group A did not show this complication as there was no remaining thyroid tissue to start hyperfunctioning. All the above complications were statistically insignificant showing again that there was no difference between the two surgical procedures with respect to the above complications.

Permanent hypothyroidism however, was noted in 131 patients(74.8%) in Group A and 103 patients (33.7%) in Group B with a very significant P Value of <0.001. This complication is easily treated with thyroxine supplementation as already mentioned. Exophthalmos regressed from 4.2 mm to 3.8 mm at an average among the 44 patients who presented with this condition from Group A. In group B patients also there was a decrease in the exophthalmos from 4.4 to 3.9mm.

Thyroid antibody titres showed declining values in the post operative as compared to pre operative values in both groups, with a greater decrease in those undergoing total thyroidectomy.

DISCUSSION

In order to prevent the recurrence of hyperthyroidism in Grave's disease the critical mass of the thyroid remnant has to be reduced to near zero. This can be achieved only by doing a total thyroidectomy. Hypoparathyroidism can be avoided by harvesting and autotransplantation of the parathyroid gland in all cases. In our series, the incidence of hypoparathyroidism was low (2.8%). By removing adequate volume of thyroid tissue, the stimuli for TSH antibody production is reduced thereby preventing the progression of ophthalmopathy. In our study, in patients presenting with exophthalmos, on follow up there was no progression of this condition in the subgroup of patients undergoing total thyroidectomy. In a few cases slight regression of exophthalmos as measured by optical micrometer was recorded (Table 3). There were no cases of recurrent hyperthyroidism following total thyroidectomy due to obvious reasons. Subtotal thyroidectomy on the other hand has the advantage of a lower incidence of hypothyroidism. But as recurrent hyperthyroidism is more difficult to treat (radioiodine therapy) the surgical procedure adopted should aim at reducing its incidence. Hypothyroidism on the other hand is a tolerated complication and can be effectively treated by the administration of thyroxine.

Also, a high dietary intake of iodine is associated with a higher incidence of recurrence after surgery especially in coastal areas such as Chennai. Iodine excess is directly related to the development of Grave's disease itself as shown by studies done in endemic areas.2 A high iodine intake is intrinsically linked with the disease process as is evidenced by it's direct association with a high anti thyroid antibody titre.2 Hence in areas with a high iodine content, complete removal of the gland alone can bring down the antibody titres effectively. Thyrotoxic osteoporosis or hungry bone syndrome is also less likely to occur after a total thyroidectomy. Total thyroidectomy scored over the subtotal procedure in these respects.

The concept of `critical mass' or the ideal volume of remnant thyroid tissue to be left behind during a subtotal thyroidectomy for Grave's disease remains an enigmatic question today. An agreement among surgeons is yet to be reached regarding the `ideal volume'. The previous consensus on leaving a remanant weighing 4-8 gms3 was not without its drawbacks. The exact measurement of this volume proved difficult. Further, any small excess caused an unacceptably high recurrence rate of hyperthyroidism. In this setting the questions to be answered are as follows

  1. Is there really a true critical mass?
  2. If so, is it practical to measure this critical mass?
  3. If the `critical mass' is reduced to zero as in total thyroidectomy the recurrence is nil. Therefore, is the achievement of a critical mass of `zero' the most appropriate treatment in Grave's disease?

The cardinal factors to be considered in deciding the mode of surgery in primary thyrotoxicosis (Grave's disease) include the frequency of occurrence of recurrence of hyperthyroidism postoperatively9 postoperative hypoparathyroidism, short and long term hypothyroidism postoperatively and the degree of exophthalmos.4

The recurrence of hyperthyroidism is controlled by the interplay of several factors. The level of TSH post operatively and the volume of remnant tissue being the most important. A high level of TSH in the presence of remnant thyroid tissue with a integral amplification of the action of TSH by the presence of Growth factors such as IGF (Insulin like Growth factor), EGF (Epidermal Growth factor), TNFa (Tumour Necrosis Factora) predisposes to a high recurrence rate.5 The high recurrence rate can be altered by reducing the volume of thyroid remnant to a critical mass of `zero', this being achieved by a total thyroidectomy. Further, during this procedure the incidence of hypoparathyroidism can be reduced by the intraoperative harvesting of the parathyroid glands in every case and autotransplantation in the forearm (Brachioradialis) or sternomastoid muscle. Hypothyroidism, relatively uncommon in a subtotal thyroidectomy, is commoner following total thyroidectomy. (Table 1)

TSH binding inhibitory immunoglobulin (TBII) or TSH receptor antibody levels are being increasingly used today as a predictor of recurrence of hyperthyroidism post operatively. Results have shown that an elevated level of these antibodies predispose to recurrence of hyperthyroidism postoperatively.6,7 Also, greater the volume of thyroid tissue removed, greater is the immunological as well as hormonal remission.8

The level of TBII antibody is influenced by the quantity of TSH receptors present on the thyroid gland. Therefore, a reduction in the number of these receptors reduces the intensity of the antigenic stimuli required in producing TSH antibodies. An effective clearance of TSH receptors can be achieved by reducing the critical mass to zero as in total thyroidectomy.

Although the exact cause of thyrotoxicosis related ophthalmopathy remains obscure, evidence is accumulating that the autoimmune process of exophthalmos is related to a cross reacting antibody between the eye muscles, retro orbital fatty tissues and the thyroid microsomes.9 This evidence is given further impetus by the transient increase in exophthalmos soon after thyroid surgery. This effect has been postulated to occur due to the excess of antibody and the reduction in quality of thyroid antigens needed to neutralise these antibodies following surgery, the antibodies therefore being directed solely against the orbital tissues. However, on a long term basis, in most cases, the eye changes run a benign course and regress after surgery.10 In a few cases this condition can become progressively severe requiring urgent intervention.

CONCLUSION

Total thyroidectomy if performed by skilled hands for Grave's disease does not present more complications such as recurrent laryngeal nerve palsy, recurrent hyperthyroidism, hypoparathyroidism as compared to subtotal thyroidectomy. The reduction of the `critical mass' to zero as is the case with Total Thyroidectomy prevents the relapse of hyperthyroidism, which is an important factor especially in an iodine rich coastal area like Chennai. We also noticed that following total thyroidectomy there is regression of thyrotoxicosis associated ophthalmopathy, although this finding did not attain statistical significance.

REFERENCES

  1. Misra SK, Misra A, Agarwal A, et al. Total thyroidectomy for benign thyroid disorders in an endemic region. World J Surg 2001; 25: 307-309.
  2. Schleusener H, Peters H, Fischer C. Recurrence in Basedow's disease treated with thyrostatic drugs. Schwerz Med Wochenscher 1990; 26: 768-71.
  3. Kasuga Y, Sugenoya A, Kobayashi S, et al. Clinical evaluation of response to surgical treatment of Grave's disease. Surg Gynecol Obstet 1990; 170: 327.
  4. Editorial. Autoimmune endocrine exophthalmos. Lancet 1982; 2: 1378.
  5. Bergland J, Aspelin P, Bondeson AG, et al. Rapid increase in volume of the remnant after hemithyroidctomy does not correlate with serum concentration of thyroid stimulating hormone. Eur J Surg 1998 ; 164: 257-62.
  6. Kasuga Y, Sugenoya A, Kobayashi S, et al. Significance of values of thyrotropin binding inhibitor immunoglobulin and appearance of intrathyroidal lymphocytes after subtotal thyroidectomy for Grave's disease. Am J Surg 1994; 178: 589.
  7. Farid NR, Bear JC. The human major histocompatibility complex and endocrine disease. Endocr Rev 1981; 2: 50.
  8. Sugino K, Ito K, Ozaki O, et al. Post operative changes in thyrotropin binding inhibitory immunoglobulin level in patients with Grave's disease. World J Surg 1999;23: 727-31.
  9. Abe Y, Sato H, Naguchi N, et al. Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Grave's Disease. World J Surg 1998; 229: 714-7.
  10. Witte J, Goretzki PE. Surgery for Grave's disease. Total vs Subtotal thyroidectomy. World J Surg 2000;24: 1303-11.

Copyright 2002 - Indian Journal of Surgery. Also available online at http://www.indianjsurg.com


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