3.3.8 Surgery for thyrotoxicosis

Surgical intervention plays a critical role in the management of thyrotoxicosis. Despite this, radioactive iodine is still the most popular treatment modality in the USA. Thyrotoxicosis, the condition of hyperthyroidism, is due to the increased secretion of thyroid hormone, and may be caused by toxic solitary nodules, toxic multinodular goitre (Plummer’s disease), or diffuse toxic goitre (Graves’ disease). Graves’ disease is the condition of goitre and associated clinical features of tachycardia and bulging eyes described by Dr Robert James Graves (1797–1853) in 1835 (1). Understanding the pathophysiology of the condition of thyrotoxicosis is essential in the appropriate selection of surgical candidates and planning the most suitable technique. Generally, accepted indications for thyroidectomy for thyrotoxicosis include: suspicion of malignancy by physical examination (firmness, irregularity, or attachment to local structures) or by fine-needle aspiration cytology of nodules; pregnancy; women desiring pregnancy within 6–12 months of treatment; lactation; medical necessity for rapid control of symptoms (patients with cardiac morbidity); local compression (pain, dysphagia); recurrence after antithyroid drug treatment; fear of radioactive iodine treatment; resistance to ¹³¹I or antithyroid drugs; or thyroid storm unresponsive to medical therapy. Other more relative indications for thyroidectomy also include: large goitres greater than 100 g that are less likely to respond to radioactive treatment and require a large treatment dose of ¹³¹I; severe Graves’ ophthalmopathy; poor compliance with antithyroid drugs; children and adolescents; a large, bothersome, and unsightly goitre; amiodarone-induced thyrotoxicosis, in cases when medical treatment is ineffective and amiodarone is necessary to treat cardiac disease; or hypersensitivity to iodine.

There are multiple advantages of thyroidectomy compared to other treatment modalities. Thyroidectomy is the fastest alternative for controlling hyperthyroidism. In most cases the medical preparation for the procedure can be achieved in 4–6 weeks (2), whereas antithyroid drugs require continuous therapy for 6–12 months with close medical surveillance. Radioactive iodine usually takes 2–6 months to become effective. Additionally thyroidectomy avoids the severe side effects of prolonged thionamide and/or radioactive iodine treatment (3). Decisions about such management strategies include issues that may have future consequences. For example, for women of childbearing age, most experts recommend avoiding pregnancy for 4–6 months after radioactive iodine treatment (4). Planning for such a decision should be discussed with the patient and family. Additionally, patients treated with radio-iodine have an increased mortality from multiple causes (5).

Surgical treatment of thyrotoxicosis is highly successful and provides a reliable cure with a recurrence of hyperthyroidism of 0.7–9.8% depending upon the size of the thyroid remnant (6). When weighing options, radioactive iodine treatment has a comparable efficacy but at 6 months only 50% of the patients are euthyroid and eventually all patients become hypothyroid. For patients treated with antithyroid drugs, the overall relapse rate exceeds 80% after treatment is discontinued (7).

Hypothyroidism is a common complication of ablative treatments and is found in 36% of the patients at 8.5 years and 50% of the patients at 12 years. Following the first year of treatment, patients have about a 3% risk per year of developing hypothyroidism. Radioactive iodine is of limited success in clinical ablation of the toxic nodule (64% remain palpable at 8.5 years). Comparatively, the rate of hypothyroidism after surgery depends on the remnant size, but is less frequent in patients who undergo a subtotal thyroidectomy than in those treated with radioactive iodine (8).

Thyroidectomy removes coexisting occult thyroid nodules. Approximately 13% of patients with Graves’ disease have nodules that are suspicious for carcinoma (9) and small thyroid carcinomas are found in up to 9.8% of the patients (2). This risk is slightly increased in patients treated with radioactive iodine. A cooperative study encompassing 36 000 patients demonstrated a prevalence of thyroid cancer twice as high in patients with Graves’ disease versus euthyroid patients (10). An increased aggressiveness has been reported for thyroid cancers arising in patients with Graves’ disease, as some thyroid cancers are thought to be stimulated by the thyroid-stimulating antibodies (11).

For the paediatric population, Graves’ disease is associated with poor school performance, decreased attention, and frequent mood changes (12). Adverse effects of antithyroid drugs are higher than in the adult population and long-term compliance is poor. Such factors lead to a higher relapse rate. Thyroidectomy is beneficial because it has an immediate effect in controlling symptoms and effects of hyperthyroidism in thyrotoxic children. The relapse rate is below 4% (12). Most importantly, the risks of thyroidectomy in children are comparable to adults when the procedure is performed in a specialized centre (12).

From the North American perspective, surgical management is the most cost-effective strategy across a wide range of ages, with the exception of those patients with significant comorbidities that would increase surgical mortality (13). The specific advantage is age-related and, for patients older than 60 years, radioactive iodine appears to be a more cost-effective alternative.

Graves’ ophthalmopathy is present in approximately 50% of patients with Graves’ disease and in up to 8% of cases may lead to malignant exophthalmos. Radioactive iodine therapy is associated with a small but definitive risk of progression or development of ophthalmopathy (14). It is well documented that a course of steroids can prevent the exacerbation of Graves’ ophthalmopathy in virtually every case, but the side effects of steroid treatment for Graves’ ophthalmopathy include the appearance of cushingoid features (14), osteopenia, cerebral haemorrhage, atrial fibrillation, and heart failure (15). Controlled trials comparing the effect of subtotal versus total thyroidectomy on Graves’ ophthalmopathy found no significant differences (16, 17). In a recent trial, near-total thyroidectomy followed by radioactive iodine therapy was superior to total thyroidectomy alone for controlling progression of Graves’ ophthalmopathy (0% versus 25% of Graves’ ophthalmopathy progression at 9 months) (18). Considering these results, total thyroid ablation, when it can be done safely, is recommended for patients with severe ophthalmopathy to decrease the risk of progression.

The surgical management of goitre was greatly advanced by Theodor Kocher, whose techniques significantly reduced the morbidity and mortality of thyroidectomy; he was awarded the Nobel Prize for his work in 1909. He advocated subtotal thyroidectomy as the surgical treatment for Graves’ disease and this became the standard therapy until the introduction of radioactive iodine in the 1940s (19). The various operative approaches for patients are total or near-total thyroidectomy, subtotal thyroidectomy which leaves bilateral remnants of about 2.5 g, and total lobectomy and contralateral subtotal lobectomy (Hartley–Dunhill procedure) which leaves thyroid remnant of about 4–5 g on one side. The Hartley–Dunhill operation results in leaving a larger unilateral remnant on only one side. The advantage of this procedure over bilateral subtotal thyroidectomy is that it decreases the small risk of nerve injury on the remnant side and is easier to tailor the precise size of the thyroid remnant. It also decreases the risk of injury to the recurrent laryngeal nerve to one side of the neck in the event of a recurrence requiring reoperation. There are no differences in mortality, recurrent laryngeal nerve palsy, hypocalcaemia, wound complications, or recurrence rate between the two techniques (bilateral versus unilateral remnant) of subtotal thyroidectomy (20, 21).

In the cases of subtotal thyroidectomy, remnant size is directly related to the risk of developing postoperative hypothyroidism or recurrent hyperthyroidism. There are other factors associated with a higher risk of recurrent hyperthyroidism including young age, high iodine intake, Graves’ ophthalmopathy, high thyroid-stimulating immunoglobulin (TSI) titres, and lymphocytic infiltration of the thyroid gland. The coexistence of Hashimoto’s disease may decrease the risk of recurrence so that a larger thyroid remnant can be left in such patients.

A meta-analysis of 7241 patients on 35 studies compared the results after total thyroidectomy (TT) and subtotal thyroidectomy (ST) for Graves’ disease (22). In this study there was no difference in recurrent laryngeal nerve palsy (0.9% for TT versus 0.7% for ST), transient hypocalcaemia (9.6% for TT versus 7.4% for ST), or permanent hypoparathyroidism (0.9% for TT versus 1.0% for ST). Sixty per cent of the patients in the subtotal thyroidectomy group achieved euthyroidism and 29% developed hypothyroidism; the recurrence rate for this group was 7.9% (versus 0% for the TT group). In contrast with these findings, other controlled trials have described a lower risk of permanent hypoparathyroidism for patients treated with subtotal thyroidectomy (17).

The rationale for recommending total or near-total thyroidectomy for patients with Graves’ disease is based on a significantly reduced risk for recurrence, reduced risk of requiring ¹³¹I ablative therapy or reoperation, comparable morbidity, and removal of coexisting pathology. The surgeon should be completely confident of the viability of the parathyroid glands and function of the recurrent laryngeal nerve on the initial side when planning a total thyroidectomy; if this is not the case, a Hartley–Dunhill procedure should be considered.

Before surgical intervention, the patient should be rendered euthyroid using thionamides coupled with a β-blocker (Table 3.3.8.1). Thionamides can induce granulocytopenia or agranulocytosis. Because of this, baseline white blood cell counts should be obtained before use. In young patients with hyperthyroidism, an increased alkaline phosphatase suggests an increased ‘bone turnover’; it usually takes about 8 weeks of treatment with thionamides before the alkaline phosphatase level returns to normal.

Preoperative β-blockade is recommended to control symptoms of tachycardia, tremor, restlessness, and anxiety and to decrease gland vascularity, which usually makes for a technically easier operation. β-blockade is continued up to the time of surgical intervention. If necessary, intravenous β-blockade with esmolol or propranolol can be titrated to control tachycardia or arrhythmia during the operation, although this should not be necessary for a properly prepared patient. β-blockade is contraindicated for patients who have a history of asthma, obstructive airway disease, bradycardia, or symptoms mimicking congestive heart failure. In any of these cases, the use of thionamides should be extended to 4–6 weeks preoperatively.

Iodides, in addition to reducing the uptake of iodide and inhibiting the release of thyroid hormone, also decrease the vascularity of the thyroid gland. For this reason, Lugol’s solution or a saturated solution of potassium iodide (SSKI) is recommended for about 10 days preoperatively. Although serum triiodothyronine (T₃) and thyroxine (T₄) levels fall initially in all patients, this occurrence is incomplete and transient; therefore iodine should not be used alone or beyond 2 weeks. Both iodides and β-blockers should be given together or with a thionamide in preparation for an operation. In patients with intolerance to thionamides, noncompliance, or the necessity of emergency thyroidectomy, β-blockade plus iodide or steroids may be used.

Sodium ipodate is an oral cholecystographic agent that has several effects on thyroid hormone metabolism. Sodium ipodate releases iodine after it is metabolized, thereby inhibiting the synthesis and secretion of thyroid hormones and it is also a potent inhibitor of the peripheral conversion of T₄ to T₃. Usually, a total dose of 3 g is utilized and this can be administered starting 3 or 4 days before surgery with similar effectiveness (23). Steroids such as prednisone are added to prevent adrenal exhaustion and to decrease the extrathyroidal conversion of T₄ to T₃ in patients with severe hyperthyroidism or thyroid storm (24). In patients who report voice changes or those with previous neck surgery, preoperative vocal cord examination should be routinely performed.

The ideal surgical therapy depends on the aetiology of the disease. In Graves’ disease and/or in toxic multinodular goitre, a subtotal thyroidectomy leaving approximately 5 g of thyroid is the procedure of choice. A toxic adenoma confirmed by radionuclide scan can be treated by excision or a unilateral lobectomy. If coexisting thyroid pathology is present, such as thyroid carcinoma, a total thyroidectomy is recommended (25). Thyroid operations are associated with minimal morbidity and almost negligible mortality when performed by experienced surgeons.

The patient is placed in the supine position with the neck hyperextended. A rolled drape is placed longitudinally along the patient’s spine to mobilize the thyroid gland anteriorly and cephalad. The site of the incision is marked approximately 1 cm below the cricoid cartilage, which places the incision directly over the isthmus of the thyroid gland. Superior and inferior skin flaps are raised in the subplatysmal plane and the midline raphe is opened. The strap muscles are dissected from the anterior surface of the gland and retracted laterally. The carotid sheath is retracted laterally, tensing the middle thyroid veins which are transected close to the gland. Careful inspection for the parathyroid glands and recurrent laryngeal nerve begins once the middle thyroid vein is divided. The gland is rotated medially creating tension on the inferior thyroid artery and usually bringing the recurrent laryngeal nerve into view (Fig. 3.3.8.1). If the nerve is not identified at this point, it can be recognized with careful dissection along the capsule of the gland at the level of the cricoid cartilage, where it enters the larynx posterior to the cricothyroid muscle. The right recurrent laryngeal nerve courses obliquely after travelling around the subclavian artery and the left recurrent laryngeal nerve travels almost vertically after traversing around the ligamentum arteriosum.

At this point, the surgeon must choose between controlling the superior or inferior thyroid pedicle based on his/her personal preference. If the superior pedicle is addressed first, the superior thyroid artery and vein should be ligated individually as low as possible on the thyroid parenchyma to avoid possible injury to the external laryngeal nerve. No thyroid tissue should remain cephalad to the point of ligation. The external laryngeal nerve is responsible for high-pitched sounds and is referred to as the ‘Amelita Galli-Curci nerve’. Care is taken to avoid injury to this nerve by dissecting lateral to the cricothyroid muscle, where the external laryngeal nerve can often be identified.

The upper parathyroid glands are more consistent in position and can usually be identified at the level of the cricoid cartilage. The thyroid lobe is retracted anteriorly and medially and the tissues on the undersurface carefully dissected. The lower parathyroid glands are almost always anterior to the recurrent nerve and 80% of the time are within 1 cm of the junction of the inferior thyroid artery and the nerve. A broad vascular pedicle is left around the parathyroid glands to minimize the risk of devascularization. In the rare event that this cannot be accomplished, the parathyroid should be excised, its identity confirmed by frozen section analysis, and 1-mm sections autotransplanted into separate pockets in the sternocleidomastoid muscle. Once the thyroid is separated from the parathyroid glands and the recurrent nerve, the inferior thyroid veins can be safely ligated. The gland is then dissected from the anterior surface of the trachea. A dense posterior suspensory ligament (Berry’s ligament) firmly attaches the thyroid to the first two tracheal rings. This is the most common site of nerve injury and special care must be taken when bleeding occurs at this site. There is a small artery and vein that are situated in this ligament, but no vessels should be clamped in this area until the recurrent laryngeal nerve is fully visualized. The bleeding can be controlled by gentle pressure with a peanut sponge.

For subtotal resection a similar process is repeated on the opposite side, except that a thyroid remnant should be left in the area of the intersection of the recurrent nerve and cricothyroid muscle. The inferior thyroid artery is also usually kept intact to provide a blood supply to the remnant. Remnant size can be approximated by matching it to a measured and weighed tissue sample taken from the previously removed contralateral lobe. If the indications call for total thyroidectomy, no remnant is left in the neck. For patients with Graves’ disease, we prefer the Hartley–Dunhill operation, which is a total lobectomy on one side and a subtotal or near-total lobectomy on the other, leaving 2–6 g depending on the desired outcome. For children, a smaller thyroid remnant is necessary because recurrence is more likely.

Perfect haemostasis is achieved. The sternothyroid muscles are approximated leaving a small opening in the midline at the suprasternal notch to enable blood to escape and to make bleeding more evident if it were to occur postoperatively. The platysma muscle is aligned and approximated, and the skin is closed with a subcutaneous suture or winged clips. Dressings are applied and the patient is wakened, extubated, and transported to the postoperative recovery area. Most patients are ready for discharge on the following morning.

There are several schools of thought on how much thyroid remnant to leave. Some surgeons aim to create hypothyroidism and not achieve a euthyroid state in order to avoid recurrence, while others aim for euthyroidism by leaving an appropriate amount of thyroid tissue (26). In a range of 2–8 g, increasing the remnant size by 1 g decreases the rate of postoperative hypothyroidism by about 10%. This calculation is based on a 70% rate of hypofunction if 2 g are left intact. However, increasing the remnant size to above 10 g does not further decrease hypothyroidism but rather increases the risk of recurrence.

Some surgeons leave 3–5 g of tissue on both sides of the neck. This procedure is associated with a recurrence rate of about 10% and a hypothyroid rate of 10% (27). We generally aim to leave between 4 to 7 g of thyroid remnant on one side of the neck when we wish to render the patient euthyroid. A smaller remnant or no remnant is left in children because recurrence is more likely; the same applies to patients in whom radioactive iodine therapy is undesirable or those with severe complications following antithyroid drugs.

Specific complications after thyroid surgery for thyrotoxicosis include the following in order of importance: bleeding, recurrent laryngeal nerve injury, hypocalcaemia due to parathyroid hypofunction or hungry bone disease, as well as infection, thyroid storm, keloid formation, and seroma. Luckily, these complications are rare and 99% of patients can be discharged on the first postoperative day. Patients rendered euthyroid with antithyroid drugs or Lugol’s solution before surgery do not require these medications postoperatively. If β-blockade was used preoperatively it should be continued for 3–5 days postoperatively because the half-life of thyroid hormone is about 1 week and the half-life of propranolol is 2–4 h.

Thyroid storm is exceedingly rare today. Treatment for such patients includes intravenous β-blockers, oxygen, cooling, sedation, intravenous steroids, sodium ipodate, hydrocortisone, and propylthiouracil in an intensive care setting. Aspirin should be avoided in the management of hyperthermia because it increases free thyroid hormone levels and may exacerbate the condition (28). The primary cause of thyroid storm is probably the marked increase in β-adrenergic effects rather than an acute increase in thyroid hormone concentration.

All patients after a thyroid operation should be carefully evaluated for postoperative bleeding. If any patient develops respiratory distress within 24 h of the thyroid operation, it is due to a neck hematoma until proven otherwise. Injury to the external laryngeal nerve may not be noticeable in some patients but can be a major disability in others who enjoy singing or speaking publicly. Unilateral recurrent laryngeal nerve injury occurs in 1–2% of patients and results in hoarseness and aspiration. Bilateral injury manifests as respiratory distress although patients may be able to speak, which is often confusing to the caring clinician. Bilateral vocal cord paralysis is exceptionally rare but when present often requires prolonged intubation (2–7 days) or tracheotomy.

Temporary hypocalcaemia (serum calcium <8.0 mg/dl or 2 mmol/L) occurs relatively frequently after thyroidectomy for hyperthyroidism. The incidence is as high as 46%, although less than one-half of these patients are symptomatic. Causes can be attributed to hungry bone syndrome due to postoperative reversal of thyrotoxic osteodystrophy, release of calcitonin during operative manipulation, or damage, devascularization, or inadvertent removal of the parathyroid glands during the surgery. Permanent hypoparathyroidism is a serious and potentially life-threatening complication that requires the patients to be on calcium and vitamin D permanently. Patients who undergo a total thyroidectomy for Graves’ disease are considered by some to be at high risk for developing permanent hypoparathyroidism. However, in a recent series of 4426 patients, there was no difference in the incidence of hypoparathyroidism after total thyroidectomy in patients operated on for Graves’ disease (1.5%) versus other conditions (1.7%) (29).

We recommend monitoring serum calcium levels at 5 and 20 h after thyroidectomy, and repeat measurements if low. Treatment is not usually necessary unless the value drops below 7.5 mg/dl or 1.875 mmol/L, or symptoms develop. Symptoms may be subtle, including tingling or numbness of the perioral area or fingertips, anxiety, paraesthesias, muscle cramps, and, if untreated, convulsions. For acute symptoms, oral calcium 1–2 g every 4–8 h is given. If the calcium level falls despite this treatment, calcium gluconate or chloride, 1–2 g every 4 h, is given intravenously. It is essential to be certain that no extravasation occurs as it can cause tissue necrosis. Calcitriol (0.25–0.75 µg twice daily) is useful for profound hypocalcaemia and phosphate binders should be reserved for patients with hyperphosphataemia.

Thyroid function following thyroidectomy depends on the size and function of the thyroid remnant. Postoperative hypothyroidism ranges from 2% to 48% and recurrent hyperthyroidism ranges from 0% to 15%. Comparison among studies is difficult because of: (1) variations in patient selection, comparing those with toxic diffuse goitres, toxic multinodular goitres, and toxic adenomas; (2) different definitions of euthyroidism; and (3) inaccurate estimation of the size of the thyroid remnant. Thyroid function should be initially assessed with measurements of T₃, T₄, and thyroid-stimulating hormone (TSH) levels. The best time to judge whether a patient is hypothyroid is at least 3–6 months post-thyroidectomy. At 6 months, 20% of those patients with initial postoperative hypothyroidism will be euthyroid and most of the patients with permanent hypothyroidism will be documented.

For most patients, TSH is the only thyroid function test that is necessary, but T₃ and free T₄ are helpful in patients who have been treated for possible postoperative hypothyroidism because TSH levels may not accurately reflect the clinical state in patients who have been treated for hyperthyroidism. Most patients who develop permanent hypothyroidism after subtotal thyroid resection do so within 2 years of surgery. Every year thereafter the rate is 0.7% or lower, which compares to a 3% increase each year thereafter with radioactive iodine treatment. All patients should be monitored with a yearly serum TSH level.