Subtotal thyroidectomy is an established and effective form of therapy for Graves' disease, providing the patient has been suitably prepared for surgery. In competent hands, the risk of hypoparathyroidism or recurrent nerve damage is under 1%, and the discomfort and transient disability attendant upon surgery may be a reasonable price to pay for the rapid relief from this unpleasant disease. In some clinics it is the therapy of choice for most young male adults, especially if a trial of antithyroid drugs has failed. Total thyroidectomy may be preferred in patients with serious eye disease or high TRAb levels, in order to keep down the incidence of recurrence ²⁰¹.  With other effective methods available, it is necessary for the physician and the patient to decide on the form of therapy most suitable for the case at hand. Because of the potential but unproved risks of ¹³¹I therapy, it is not always possible to make an entirely rational choice; the fears and prejudices of the physician and the patient will often enter into the decision.
 
Surgery is clearly indicated in certain patients. Among these are (1) patients who have not responded to prolonged antithyroid drug therapy, or who develop toxic reactions to the drug and for whatever reason are unsuitable for ¹³¹I therapy; (2) patients with huge glands, which frequently do not regress adequately after ¹³¹I therapy; and (3) patients with thyroid nodules that raise a suspicion of carcinoma. 
    Stocker et al have reviewed the problem of nodules in Graves’ glands.  They found that 12% of Graves’ patients had cold defects on scan, and among these half were referred for surgery.  Six of 22, representing 2% of all Graves’ patients, 15% of patients with cold nodules, 25% of patients with palpable nodules, and 27% of those going to surgery, had papillary cancer in the location corresponding to the cold defect.  Of these patients, one had metastasis to bone and two required multiple treatments with radioiodine.  These authors argue for evaluating patients with a thyroid scintigram and further diagnostic evaluation of cold defects(201a). 
    Subtotal or near total thyroidectomy is often the treatment of choice for patients with amiodarone induced thyrotoxicosis, since response to ATDs is typically poor, and RAIU can not be given. Surgery may also have a place in therapy of older patients with thyroid storm and/or cardiorespiratory failure , who do not respond rapidly to intensive medical therapy(202a).
    Contemporary data indicate that exophthalmos may be exacerbated by RAI therapy⁸⁰ ,although in some studies appearance of progressive ophthalmopathy was about the same after treatment with ¹³¹I as with surgery,⁷⁹  Thus, in the presence of serious eye signs, treatment with antithyroid drugs followed by surgery is an important alternative to consider, and total thyroidectomy is preferred ^201,204. The preferential use of surgery rather than radioactive iodide in the management of patients with severe Graves’ ophthalmopathy, and the greater, more frequent exacerbation of eye disease after RAI therapy, has been supported in a number of studies including those by Torring et al ^204a, Moleti et al 204b, and  De Bellis et al ^204c. Marcocci et al, in contrast, report that near-total thyroidectomy had no efffect on the course of ophthalmopathy in a group of patients who had absent or non-severe preexisting ophthalmopathy.  The relevance of this to patients with more severe ocular disease is uncertain, since it is logical to expect that in these patients there would be no effect of removing antigens, if they lacked any tendency to develop ophthalmopathy ^204d. Moleti et al recently reported on 55 patients with Graves’ disease and mild to moderate Graves’ ophthalmopathy, who underwent near-total thyroidectomy, and of whom 16 had standard ablative doses of radioactive iodide.  They found that the course of  ophthalmopathy, both short and long term after treatment, was significantly better in the group of patients who underwent thyroidectomy and ¹³¹I ablation, and suggest that this is a more effective means of inducing and maintaining ophthalmopathy inactive  (204e).

More enthusiastic surgeons have in the past recommended surgery for all children as the initial approach, claiming that there is less interference with normal growth and development than with prolonged antithyroid drug treatment.¹⁹¹ Therapy for childhood thyrotoxicosis is discussed further below.

The rate of patient rehabilitation is probably quickest with surgery. Although the source of hormone is directly and immediately removed by surgery, the patient usually must undergo one to three months of preparation before operation. The total time from diagnosis through operative convalescence is thus three to four months. Antithyroid drugs, in contrast, provide at best only 30 - 40% permanent control after one year of therapy. Iodine-131 can assuredly induce prompt remission. Low dose protocols, as noted, are plagued by a need for medical management and retreatment over one to three years before all patients are euthyroid. Treatment with higher doses provides more certain remission at the expense of hypothyroidism.

There are several strong contraindications to surgery, including previous thyroid surgery, severe coincident heart or lung disease, the lack of a well-qualified surgeon, and pregnancy in the third trimester, since anesthesia and surgery may induce premature labor.

Antithyroid drugs of the thiocarbamide group are employed to induce a euthyroid state before subtotal thyroidectomy when surgery is the desired form of treatment. Two approaches are used. PTU or methimazole may be administered until the patient becomes euthyroid. After this state has been reached, and while the patient is maintained on full doses of thiocarbamides, Lugol's solution or a saturated solution of potassium iodide is administered for 7 - 10 days. This therapy induces an involution of the gland and decreases its vascularity, a factor surgeons find helpful in the subsequent thyroidectomy. The iodide should be given only while the patient is under the effect of full doses of the antithyroid drug; otherwise, the iodide may permit an exacerbation of the thyrotoxicosis. Alternatively patients may be prepared by combined treatment with antithyroid drugs and thyroxine. It is not obvious that one method is superior to the other.
    Severely ill patients can be prepared for surgery rapidly by combining several treatments-iopanoic acid  500mg bid, dexamethasone 1mg bid, antithyroid drugs, and beta-blockers(204f)..

Pre-treatment should have the patient in optimal condition for surgical thyroidectomy. By this time the patient has gained weight, the nutritional status has been improved, and the cardiovascular manifestations of the disease are under control. At the time of surgery, the anesthesia is well tolerated without the risk of hypersensitivity to sympathoadrenal discharge characteristic of the thyrotoxic subject. The surgeon finds that the gland is relatively avascular. Convalescence is customarily smooth. The stormy febrile course characteristic of the poorly prepared patient in past years is rarely seen.

Reactions to the thiocarbamide drugs occasionally occur during preparation for surgery. If the problem is a minor rash or low-grade fever, the drug is continued, or a change is made to a different thiocarbamide. More severe reactions (severe fever or rash, leukopenia, jaundice, or serum sickness) necessitate a change to another form of therapy, but no entirely satisfactory alternative is available. One course is to administer iodide and propranolol and proceed to surgery. In some patients, it is best to proceed directly to ¹³¹I therapy if difficulties arise in the preparation with antithyroid drugs.

Propranolol has been used alone or in combination with potassium iodide¹⁹² in preparation for surgery, and favorable results have generally been reported.^193-195 This procedure is doubtless safe in the hands of a medical team familiar and experienced with this protocol and willing to monitor the patient carefully to ensure adequate dosage. It is safe to use in young patients with mild disease, but we are reluctant to advise it as a standard protocol. We use propranolol as an adjunct, or combined with potassium iodide as the sole therapy only when complications with antithyroid drugs preclude their use and surgery is strongly preferred to treatment with ¹³¹I.

Amiodarone induced hyperthyroidism is typically difficult to manage, as described in Chapter 13. Administration of iopanoic acid, 1 gm daily for 13 days, has been shown to provide successful pre-operative therapy, reducing T3 levels to normal (195a).

The standard operation is a one-stage subtotal thyroidectomy. General anesthesia is standard, but cervical plexus block and out-patient surgery is employed by some surgeons ^192.1,192.2.  Some clinicians argue for total-thyroidectomy in an effort to reduce recurrence rates, and point out that this operation seems to reduce anti-thyroid autoiommunity and reduces the chance of exacerbation of ophthalmopathy. The surgical technique is discussed in Chapter 21. Permanent cure of the hyperthyroidism is produced in 90 - 98% of patients treated this way. The amount of tissue left behind is about 4-10 grams, but this amount is variable. Taylor and Painter¹⁹⁶ found that the average volume of this remnant in 43 patients achieving a remission was about 8 ml, and Sugino et al recommended leaving 6 grams of tissue.^196a The toxic state recurred in only two patients in their series, and in these twice the amount of tissue mentioned above was left. Ozaki also noted the importance of the amount of thyroid remaining as the principal predictor of eu- or hypo-thyroidism ^196.1.There seems however to be no relation between the original size of the thyroid and the size of the remnant necessary to maintain normal metabolism. 
    Motivated  in part by economic considerations, there has been in recent years a reevaluation of thyroidectomy done under local anesthesia as a day-surgery proceedure.  Pros and cons have recently been discussed ^196.2. In proper hands local anesthesia and prompt discharge seem acceptable, but most surgeons opt for the standard in hospital approach since it offers a more controlled operative setting and an element of safety the night after surgery.

Although surgery of the thyroid has reached a high degree of perfection, it is not without problems even in excellent hands. The complication rates at present are low.¹⁹⁷ Among 254 patients operated on at three Nashville hospitals in the decade before 1970, there was no mortality, only minor wound problems, a 1.9% incidence of permanent hypoparathyroidism, and a 4.2% recurrence rate.¹⁹⁸ Hypo-parathyroidism is the major undesirable chronic complication. Surgical therapy at the Mayo Clinic has in recent years¹⁹⁹ been associated with a 75% rate of hypothyroidism but only a 1% recurrence rate, as an effort was made to remove more tissue and prevent recurrences. There is typically an inverse relationship between these two results of surgery. In the recent experience of the University of Chicago Clinics, the euthyroid state has been achieved by surgery in 82%; 6% became hypothyroid, and the recurrence rate was 12%.²⁰⁰  6.       Palit et al. recently published a meta analysis of collected series of patients treated for Graves’ disease, either by total thyroidectomy or subtotal thyroidectomy.  Overall, the surgery controlled hyperthyroidism in 92% of patients.   There was no difference in complication rates between the two kinds of operations, with permanent laryngeal nerve injury occurring in .7 - .9% of patients, and permanent hypoparathyroidism in 1 – 1.6% of patients.  Since many surgeons have become more familiar and capable with total thyroidectomy, and this avoids the possible recurrence of disease, although possibly slightly increasing the risk of nerve or parathyroid damage, total thyroidectomy has become a common  or even preferred alternative to subtotal thyroidectomy for managing hyperthyroidism ^200a. Recurrence rates are higher in patients with progressive exophthalmos or positive assays for TRAb, suggesting that total thyroidectomy may be preferred in these cases.²⁰¹ Geographic differences in iodine ingestion have been related to the outcome. In Iceland, with a high iodine intake, postoperative hypothyroidism is less frequent, but recurrence is more common than in iodine-deficient Scotland.²⁰²

Death rates are now approaching the vanishing point.²⁰³ Of the nonfatal complications, permanent hypoparathyroidism is the most serious, and requires lifelong medical supervision and treatment. Experienced surgeons have an incidence under 1% ²⁰⁵. Unfortunately, the general experience is near 3%. More patients, perhaps 10%, develop transient post-operative hypocalcemia but soon recover apparently normal function. Perhaps these patients have borderline function that may fail in later years.

Unilateral vocal cord paralysis rarely causes more than some hoarseness and a weakened voice, but bilateral injury leads to permanent voice damage even after corrective surgery. Bilateral recurrent nerve injury may be associated with severe respiratory impairment when an acute inflammatory process supervenes and may be life-threatening. Fortunately, it is now extremely rare after subtotal thyroidectomy. Damage to the superior external laryngeal nerve during surgery (see Chapter 21) may alter the quality of the voice and the ability to shout without causing hoarseness. One may speculate whether declining skills in the techniques of subtotal thyroidectomy, attendant upon a dramatic fall in the use of this procedure, may lead to an increase in the hazards of the procedure.

Hypothyroidism, whether occurring after surgery or ¹³¹I therapy, can be readily controlled. Transient hypothyroidism is common, with recovery in one to six months.  The presence of autoimmunity to thyroid antigens predisposes to the development of hypothyroidism after subtotal thyroidectomy for thyrotoxicosis. A positive test for antibodies to the microsomal/TPO antigen was found by Buchanan et al.²⁰⁶ to correlate with an increased incidence of postoperative hypothyroidism. The incidence of hypothyroidism is certainly of importance in weighing the virtues of ¹³¹I and surgical therapy. The ability of surgical therapy to produce a euthyroid state in many patients over long-term follow-up gives it one advantage over RAI therapy, but this must be weighed against the risk of hypoparathyroidism and recurrent nerve damage.

In the immediate postoperative period, patients should be followed closely. They should ideally have a special duty nurse or family member providing watch during the first 24 hours, and a tracheotomy set and calcium chloride or gluconate for infusion should be at the bedside. During this period, undetected hemorrhage can lead to asphyxiation.  Current use of drains with constant suction helps protect against  this problem.  Transient hypocalcemia is common, resulting from trauma to the parathyroid glands and their blood supply and also possibly to rapid uptake of calcium by the bones, which have been depleted of calcium by the thyrotoxicosis.²⁰⁷ Oral or intra- venous calcium supplementation suffices in most instances to control the symptoms. The calcium may be given slowly intravenously as calcium gluconate or calcium chloride in a dose ranging from 0.5 to 1.0 g every 4-8 hours, as indicated by clinical observation and determination of Ca²⁺.

Some surgeons give their patients replacement thyroid hormone for an indefinite period after the operation in an attempt to avoid transient hypothyroidism and to remove any stimulus to regeneration of the gland. It is not obvious that this is either necessary or efficacious. In 50-70% of patients, the residual gland is able to form enough hormone to prevent even transient clinical hypothyroidism. Serum hormone levels should be determined every two to four months until it is clear that the patient does not need replacement.

Probably the thyroid remnant is not normal. It has a rapid ¹³¹I turnover rate and a small pool of stored organic iodine. Suppressibility by T₃ administration returns within a few months of operation in some patients. TSAb tend to disappear from the blood in the ensuing 3 - 12 months^208-210. After subtotal thyroidectomy, thyrotoxicosis recurs in 5 - 10% of patients, often many years after the original episode. The long term outcome of thyroid surgery for hyperthyroidism was reviewed by the Department of Surgery at Karolinska Institute and Hospital at Stockholm, Sweden.  Of 380 patients observed and treated by surgery for thyrotoxicosis, primarily by subtotal thyroidectomy, 1% developed permanent hypoparathyroidism.  Recurrent disease occurred in 2%.  The operators intended to leave less than two grams of thyroid tissue, which presumably accounts for the low recurrence rate (210.1).

Finally, adequate follow-up must be carried out after any kind of treatment of Graves' disease. Recurrence is always possible, either early or late, and there is always the threat that the ophthalmopathic problems may worsen when all else in the progress of the patient seems favorable. A surprisingly large proportion of patients who have had subtotal thyroidectomy for Graves' disease and who are clinically euthyroid can be shown to have an abnormal TRH response (excessive or depressed), and up to a third have elevated serum TSH levels.^210,211 Some of them are undoubtedly mildly hypothyroid, whereas others are close to euthyroid but require the stimulation of TSH to maintain this state. These patients should have replacement T4 therapy if the elevated TSH persists. Over subsequent years the residual thyroid fails in more patients, due either to reduced blood supply, fibrosis from trauma, or continuing autoimmune thyroiditis. After 10 years, and depending on the extent of the original surgery, 20 - 40% are hypothyroid. This continuing thyroid failure is also seen after antithyroid drug therapy with ¹³¹I and represents the natural evolution of Graves' disease.