Metastases to the Thyroid Gland

Isolated metastases from other primary cancers can occur in the thyroid gland, although they are rare.

The most common tumor type to do so is renal cell carcinoma, although it can occur from breast, lung,

and gastrointestinal carcinomas, as well as melanoma and sarcoma.62 Thyroidectomy can be useful for

control of compressive symptoms.

Preoperative Ultrasound

Cervical US plays an important role for preoperative planning prior to thyroidectomy for benign disease

and for thyroid cancer. US, which can be performed by the operating surgeon, provides important

information including determination of the size and extent of thyroid nodules which may not be

palpable on physical examination. Failure to visualize the caudal extent of the lower thyroid lobes in

large goiters indicates possible substernal extension which can be further delineated with CT.

Preoperative US can also evaluate the cervical lymph nodes in cases of thyroid cancer and particular

attention should be paid to evidence concerning imaging appearances (lack of a hilar line,

microcalcifications, and loss of the typical flattened ovoid shape) which may not be noted on physical

examination alone. Detection by US of nonpalpable lymph node metastases occurs in 24% to 39% of

patients with papillary thyroid cancer diagnosed by FNA.12,63–65 Even in patients with palpable

lymphadenopathy, US can alter the extent of lymphadenectomy in approximately 40% of patients

undergoing initial or reoperative surgery.65–67

Extent of Thyroidectomy

9 Thyroidectomy is a primary treatment for DTC and is well accepted to be both effective and safe;

however, some controversy persists about the extent of thyroidectomy necessary for low-risk patients.

It is generally agreed that surgical options (not typically equivalent) include hemithyroidectomy with or

without isthmusectomy for small (<1 cm) low-risk tumors confined to a single focus in the thyroid or

total or near-total thyroidectomy for all DTCs. Subtotal thyroidectomy is not an appropriate operation

for thyroid cancer. The advantages of total thyroidectomy for all DTCs of follicular cell origin include

(a) removal of multifocal intrathyroidal tumors; (b) use of radioiodine to localize and treat small

amounts of residual normal thyroid tissue, and more importantly, regional or distant metastases; and (c)

the ability to use serum thyroglobulin as a sensitive marker of persistent or recurrent disease. If only

thyroid lobectomy is performed, radioiodine treatment is usually not optimal because of the increased

avidity for RAI to the normal remaining thyroid lobe compared to thyroid cancer tissue, and

thyroglobulin measurements also lose their utility. It has been difficult to demonstrate a survival

advantage related to extent of thyroidectomy. However, a study comparing extent of thyroid surgery in

patients with PTC showed that patients with PTC greater than 1 cm who underwent total thyroidectomy

had a significantly lower risk of recurrence and lower mortality compared with those undergoing

thyroid lobectomy.68

Lymphadenectomy

10 Therapeutic lymphadenectomy is a well-established treatment of the clinically involved cervical

lymph nodes. In general, regional lymph node metastases are found in 30% to 40% of patients, although

wider ranges have been reported (20% to 90%).63–65 A compartment-oriented approach to

lymphadenectomy is currently preferred over the previously advocated technique of selective neck

dissection or “berry picking” (removing only grossly positive nodes) if this can be performed without

significantly increasing morbidity or mortality. Prophylactic central lymph node dissection (CLND) is a

2134

more controversial component of treatment for papillary thyroid cancer. Central compartment lymph

node involvement is both common (can be found in up to 80% of patients with clinically negative

nodes) and difficult to treat with a remedial operation in the future.12 If prophylactic CLND is to be

added to the routine performance of total thyroidectomy to treat PTC, it must be assured that the

incidence of RLN injury and hypoparathyroidism is not increased. Routine prophylactic CLND can be

considered for patients with papillary thyroid cancer and Hürthle cell cancer if it can be done without

increasing morbidity.12 Knowledge of the central neck lymph node status improves staging accuracy in

patients over 45 years of age and may influence the use of adjuvant radioiodine treatment.69 Residual

subclinical disease, as indicated by postoperative serum thyroglobulin levels, may also be decreased

using this strategy.70 Whether prophylactic central neck dissection will have any benefit to long-term

survival will be very difficult to determine given the already excellent prognosis for patients with DTC.

Radioiodine Therapy

Radioiodine may serve diagnostic and therapeutic purposes in the management of follicular-derived

thyroid cancer. Low doses are used to demonstrate remaining thyroid tissue or metastatic disease as

part of a diagnostic radioiodine scan, whereas higher doses are used for thyroid remnant ablation and

for treatment of residual and/or recurrent disease. The timing of the initial postoperative scan is

dictated by the physiology of T4 and the fact that remnant thyroid tissue or DTC must be stimulated by

elevated levels of TSH to take up RAI. Although no precise threshold has been established, a general

consensus is held that the TSH at the time of RAI should be ≥30 mIU/mL to provide adequate

stimulation for radioiodine uptake. Traditionally this has been achieved by withdrawal of supplemental

thyroxine. The half-life of thyroxine is approximately 7 days, so TSH values are significantly elevated 4

to 5 weeks after total thyroidectomy or withdrawal from thyroxine treatment. To minimize the duration

of hypothyroid symptoms, patients can be managed with T3

(liothyronine) up to 2 weeks prior to

scanning, as T3 has a much shorter half-life (8 to 12 hours) than T4

. An alternative to thyroid hormone

withdrawal is the use of recombinant human TSH (rhTSH) for 131I uptake scans and treatment.71 The

use of rhTSH avoids the long deprivation of thyroid hormone replacement and development of

hypothyroid symptoms. rhTSH can also be used to obtain stimulated serum thyroglobulin levels and 131I

whole-body scans during thyroid cancer surveillance.

Radioiodine therapy has a dual intended effect of treatment of residual thyroid cancer as well as

ablation of any thyroid remnant tissue. The utility of radioiodine ablation of the thyroid remnant in the

absence of evidence of residual thyroid cancer is debated. Radioiodine therapy is a rational adjuvant

therapy for DTC because most tumor cells retain the ability to concentrate radioiodine. Several studies

have shown a decreased rate of recurrence and increased disease-specific and overall survival when 131I

treatment is used in patients with stage III and IV diseases and with more aggressive pathologic

subtypes.72,73 Although there have been no prospective randomized trials with postoperative

radioiodine, treatment is recommended for all patients with distant metastasis, primary tumors larger

than 4 cm or with gross extrathyroidal extension and those with lymph node metastasis.12 Radioiodine

treatment is generally not recommended for tumors less than 1 cm (unifocal or multifocal) confined to

the thyroid, in cases of undifferentiated thyroid cancer or in recurrent tumors that have lost the ability

to concentrate iodine. Unfortunately as many as 30% of advanced and recurrent DTC will eventually

dedifferentiate, and a portion of these cancers will lose the ability to concentrate radioiodine due to loss

of the Na+/I− symporter function. Clinical trials are ongoing using a variety of MAPK kinase inhibitors

to reverse iodine resistance and therefore make repeat radioiodine treatment a viable option.74

External Beam Radiotherapy

External beam radiation is rarely indicated in the treatment of thyroid cancer. Invasive variants which

result in gross residual disease after surgical resection may benefit from external beam radiation to

assist with local control. This is most often a consideration with tumors that invade the

tracheoesophageal axis. This occurrence is frequent with poorly differentiated tumors, but it certainly

can complicate advanced DTC as well. It has also been considered for patients with extensive lymph

node involvement that is characterized by extranodal extension. Bone metastases are rarely treated

completely with 131I and, thus, external beam radiotherapy may be effective often in conjunction with

zoledronic acid.75 Complications of external beam radiation include skin erythema and desquamation

and tracheoesophageal mucositis and its use should be limited to cases where additional operative

attempts are unlikely.

2135

Thyroid-Stimulating Hormone Suppression

Levothyroxine therapy to suppress TSH levels below 0.1 mU/L is commonly recommended for patients

with high-risk differentiated thyroid carcinoma and between 0.1 and 0.5 mU/L for low-risk patients.12

TSH is considered a trophic factor for these cancers, however, the efficacy of suppressive therapy is

inferred from uncontrolled retrospective studies. It is important to individualize the degree of

suppression in patients, balancing the risk of recurrence with the risks of subclinical hyperthyroidism

(e.g., osteoporosis, cardiac arrhythmias). If a patient has no evidence of recurrence and has extremely

low or undetectable thyroglobulin levels 5 to 10 years after treatment, it may be appropriate to lessen

the degree of TSH suppression.

Metastatic Thyroid Cancer

In addition to radioactive iodine therapy there are multiple ongoing clinical trials of tyrosine kinase

inhibitors (sorafenib, vandetanib, sunitinib, and pazopanib) in the treatment of advanced or progressive

metastatic thyroid cancer with sorafenib recently obtaining FDA approval.76 These novel drugs act to

partially inhibit multiple tyrosine kinases including BRAF, MEK, and phosphatidylinositol 3-kinase

(PI3K), RET and VEGFR and are often used as first-line treatment of metastatic thyroid cancer

nonresponsive to radioiodine therapy prior to treatment with cytotoxic agents.

THYROID SURGERY

Thyroidectomy is a safe and effective operation for thyroid disease in the hands of an experienced

surgeon. Substantial improvements in anesthesia, antisepsis, and improved hemostasis along with the

substantial technical contributions of Albert Theodor Billroth, Theodor Kocher, and William Halsted,

among others have provided the basis of modern thyroid surgery.

Technique

There is little, if any, place for subtotal lobar resections (e.g., nodulectomy) and only an occasional role

for isthmusectomy alone. Thyroid lobectomy (hemithyroidectomy) is the total extracapsular removal of

the lobe and the isthmus while preserving the parathyroid glands, the RLN, and the EBSLN. Total

thyroidectomy is merely a matter of performing a thyroid lobectomy on the contralateral side during

the same operation. Subtotal thyroidectomy is intentional subtotal lobar resection, either unilaterally or

bilaterally, and is rarely indicated except in cases where postoperative thyroid hormone replacement is

problematic. Near-total thyroidectomy involves intentionally leaving a minor amount of thyroid tissue

to protect the insertion of the RLN and the superior parathyroid gland. When properly performed, neartotal thyroidectomy is essentially interchangeable with total thyroidectomy when considering surgical

outcomes but still requires post-operative thyroid hormone replacement.

For most thyroid procedures, the patient is placed in a supine position or a semi-Fowler position with

the arms tucked to the side. A support is placed transversely under the shoulders to aid in extending the

neck. This extension must not be too extreme or postoperative pain may occur in the occipitocervical

region.

Thyroid resection should be performed in a logical orderly sequence as follows. After skin

preparation, a curvilinear incision is made approximately one to two fingerbreadths above the clavicular

heads and not any higher than the level of the cricoid cartilage, disguised in an existing skin crease

when possible (Fig. 75-8). Subplatysmal skin flaps are raised to the level of the thyroid cartilage above,

the sternal notch below, and laterally to the sternocleidomastoid muscles. The midline raphe is opened

to expose the anterior trachea and the thyroid isthmus. The sternohyoid and sternothyroid are then

separated from the underlying thyroid lobe, and the perithyroidal and paraesophageal spaces are

entered. The middle thyroid veins, which can be identified as they course medial to lateral, anterior to

the carotid artery are divided and ligated. If a pyramidal lobe is present, it is mobilized and divided

from the fibrous tissue in any remaining thyroglossal duct tract. The anterior suspensory ligament is

divided to mobilize the superior aspect of the isthmus.

Dissection of the superior pole of the thyroid must take place in the plane directly adjacent to the

thyroid capsule after the largely avascular space between the pole and the cricothyroideus muscle is

dissected. To do so more proximally along the superior pole vessels imperils the EBSLN. This nerve is

not always visually identified during thyroidectomy, but it can nearly always be preserved by utilizing

this technique and observing the anatomy carefully. The EBSLN can often be demonstrated with the

2136

help of a stimulator used in a nerve-integrity monitoring system (see below). Capsular dissection then

continues at the inferior pole of the thyroid lobe with preservation of the inferior parathyroid gland

followed by capsular dissection of the posterolateral aspect of the thyroid gland with preservation of the

superior parathyroid gland and the RLN. Figure 75-9 indicates the plane of dissection relevant to these

steps.

Figure 75-8. With the patient’s neck extended, the line above indicates the appropriate site of incision for thyroid resection.

Camouflage within an existing skin crease is often possible.

Figure 75-9. The capsular dissection necessary to preserve well-vascularized parathyroid tissue and a fully functional recurrent

laryngeal nerve begins in the area outlined above.

Unequivocal identification of the RLN should occur early in the operation and involves visual

identification of the nerve as it emerges from the mediastinum. Palpation can aid in the process of

identification of the RLN as a slightly firm linear structure in the tracheoesophageal groove with the

lobe retracted anteromedially. Although helpful in guiding early dissection, this technique cannot

supplant visual confirmation. The RLN typically courses posterior to the thyroid. Progressive exposure

of the entire surface of the nerve until it inserts into the cricothyroid muscle will allow for identification

and preservation of nerve branches. The genu of the RLN occurs near the ligament of Berry and constant

visualization of the nerve along with gentle dissection and careful division of the ligament is important

to avoid injury.

The ability to routinely preserve well-vascularized parathyroid tissue during thyroidectomy is

mandatory for surgeons performing these operations. Normal parathyroid tissue is subtle and may be

difficult to identify. It can be distinguished from surrounding fat by a slight brownish color (similar to

the color of peanut butter) and a fine capillary vascular pattern that is not present in the adjacent fat or

thymus. If a parathyroid is inadvertently removed or is devascularized it should be morcelized and then

reimplanted into an easily accessible and viable muscle such as the sternocleidomastoid or strap muscle.

2137

Figure 75-10. Boundaries showing high-risk area of central compartment dissection involving the vascular supply to the superior

and inferior parathyroid glands and the recurrent laryngeal nerve.

Figure 75-11. The recurrent laryngeal nerve is carefully isolated and dissected free from surrounding tissue in level VI.

The central compartment level VI lymph nodes are bordered by the hyoid bone cranially, the level of

innominate artery caudally, the common carotid arteries laterally, and the prevertebral fascia

posteriorly.7 Removal of these lymph nodes is an important component of an operation to treat

clinically evident lymph node metastasis in thyroid carcinoma and may have has an important role to

offer in a prophylactic manner to improve nodal staging with its downstream effects on adjuvant

radioiodine treatment.69 To perform a CLND, the prelaryngeal (Delphian) lymph node(s) adjacent to the

pyramidal lobe is excised. After the ipsilateral thyroid lobe is completely resected, the lateral and

medial extent of dissection is defined to mobilize the level VI nodes. The superior parathyroid gland

must be carefully preserved on its vascular supply as the inferior parathyroid gland is often embedded

in the nodal tissue to be removed and often requires autotransplantation (Fig. 75-10). The cervical

portion of the RLN is exposed in a retrograde direction toward the mediastinum using gentle dissection

to divide the overlying fibrofatty and nodal tissue (Fig. 75-11). Especially on the side ipsilateral to the

primary tumor, it is important to remove the nodes located posterior to the RLN and anterior to the

prevertebral fascia in addition to the more easily removed nodes located anterior to the RLN (Fig. 75-

12). If the nerve is adequately mobilized, this can usually be accomplished en bloc and the nodes may

even be left attached to the inferior pole of the thyroid. The block of nodal tissue is then removed down

to the level VII superior mediastinal nodes at the superior margin of the innominate vein. In order to

accomplish this, the cervical thymus can either be removed or preserved. If the inferior parathyroid is

unable to be preserved on its vascular pedicle, it is autotransplanted into the adjacent muscle after

confirmation with frozen section that it is indeed parathyroid tissue and not a metastatic lymph node

(Fig. 75-13).

2138

Figure 75-12. The recurrent laryngeal nerve is carefully repositioned laterally and medially as needed to dissect all fibrofatty and

lymphatic tissue from level VI structures.

Figure 75-13. It is not uncommon for the inferior parathyroid gland(s) to become devascularized during dissection of the central

compartment. Devascularized parathyroid tissue should be retrieved, minced into 1-mm pieces, and autotransplanted to the

ipsilateral sternocleidomastoid muscle.

Advanced surgical energy instruments for bipolar vessel sealing and ultrasonic scalpels have now been

integrated into thyroid resections. The main benefit in thyroidectomy is decreased operative time.77–79

Most series indicate that complication rates (hematoma, RLN injury, and hypoparathyroidism) are

comparable to conventional techniques. Heat generation and lateral thermal spread for a particular

instrument are critical to understand and may limit safe application near the RLN and parathyroid

glands.

Intraoperative monitoring of the RLN and EBSLN function is used to varying degrees with several

commercially available nerve monitoring systems. Nerve monitoring requires measurement of vocal

cord movement or muscle action potentials with either electrodes on the endotracheal tube or needle

electrodes surgically implanted in the cricothyroid muscle. Electric stimulation of the functionally intact

RLN produces adduction of the true vocal fold and a measured evoked potential signal. Similarly,

stimulation of the EBSLN produces muscular twitch of the cricothyroid muscle. Intraoperative nerve

monitoring can clearly aid in identification of the RLN and EBSLN, especially in reoperative procedures;

however, there have been no studies demonstrating a statistically significant decrease in nerve injury

rates with nerve monitoring.80–82 Therefore, whether or not RLN monitoring is employed, prevention of

injury still requires meticulous and precise surgical technique.

Modifications to the traditional transcervical approach to thyroidectomy have been developed at

several centers with the goal of decreasing the size of the cervical incision or avoiding a cervical

incision altogether. Although the modified transcervical approaches can be minimally invasive with

smaller incisions, less dissection and possibly less postoperative pain, the remote access approaches

(transaxillary, transareolar, and “facelift”) are not necessarily minimally invasive and often require

more extensive dissection to gain access to the thyroid and should be considered purely cosmetic in

their benefits.

COMPLICATIONS

Table 75-6 Complications of Total Thyroidectomy

2139

Complications

The risk of death or major disability during thyroidectomy should be diminutive. The key outcomes by

which to measure the quality of surgical care include RLN paralysis and hypoparathyroidism (Table 75-

6). Although both complications can occur in a temporary fashion, the persistence or permanence

(defined at 6 months after operation) of these complications is a critical measure. For most surgeons,

the rate of unintended permanent RLN dysfunction should be no greater than 1% and the rate of

permanent hypoparathyroidism should be no greater than 1% to 2%.

Injury to an RLN results in temporary or permanent paralysis of the vocal cord it innervates

depending on the degree of injury and presence or absence of repair. At times the main RLN will

bifurcate exterior to its insertion into the cricothyroid muscle. In these scenarios the anterior branch

typically contains motor fibers and the posterior branch typically contains sensory fibers. Injury to these

branches can result in hoarseness and aspiration respectively or in combination if the main RLN is

injured. Depending on the specific branch or combination of branches injured, the cord may remain in a

paramedian position (also called cadaveric position) or may remain abducted. If the contralateral cord is

able to adduct to the midline or beyond, the patient may have a voice that is not particularly hoarse,

but is weak. If the cord is paralyzed in the abducted position, vocal quality is very poor because of the

difficulty in approximating the cords during speaking. The patient’s cough also has a bovine quality

where there is a lack of a sharp, percussive initiation. If both vocal cords are paralyzed, consideration of

the specific cord positions is even more critical. If both cords are paralyzed in the abducted position, the

patient may have a critically limited ability to phonate. In this situation, the patient may gradually

develop some degree of airway obstruction as the cords gradually migrate toward the midline. If both

cords are paralyzed in the paramedian position, the airway is critically narrowed. In this situation,

stridor is usually apparent very soon after extubation and an emergent procedure (e.g.,

cricothyroidotomy or tracheostomy) may be required to reestablish a patent airway. Intraoperative

recognition of RLN injury can be aided with intraoperative nerve monitoring. The particular site of

injury can often be identified by progressive distal stimulation of the visualized RLN until loss of signal

occurs. If a nerve transection is noted, intraoperative neural repair can be performed with variable

regain of function.

Because of greater anatomic variations, the EBSLN is at higher risk for injury than the RLN during

thyroidectomy.80 The symptoms of injury to the EBSLN are usually less noticeable and may be only

slightly evident to the patient, but can be important in the case of the vocal professional. Symptoms of

EBSLN injury typically include early vocal fatigue, decreased pitch range, and decreased projection

ability. Findings on laryngoscopy are subtle and include bowing and inferior displacement of the

affected vocal cord and rotation of the posterior glottis toward the injured side. Laryngeal

videostroboscopy or percutaneous electromyography of the cricothyroideus muscle may be required to

detect injury in subtle cases. Because there is no effective treatment for this condition, prevention is

extremely important.

Examination of vocal cord appearance and function can be performed with indirect or flexible

fiberoptic laryngoscopy in a routine or patient selective manner.83 Laryngoscopy is particularly useful in

patients with persistent hoarseness or change in voice quality, those with history of prior surgery in

2140