Substernal Goiter Surgery

Enlarged thyroid glands (ie, goiters) often extend in the mediastinum posterior to the sternum, making the gland, by definition, a substernal (or retrosternal) goiter. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9]} When this occurs, thyroidectomy surgery (excision of part or all of the thyroid gland) has unique considerations that are important to understand for the surgeon and patient.

This article reviews substernal goiter and focuses on substernal thyroidectomy.

Most substernal goiters are composed of nontoxic multinodular thyroid glands, but can also represent a generalized enlargement of the thyroid gland, an enlargement of one particular nodule, or the inferior extension of thyroid carcinoma. Most (approximately 90%) substernal thyroid masses are benign goiters. ^{[10, 11, 12, 6, 13, 14, 15]}

Goiters are often idiopathic in etiology but may be caused by the following:

• Iodine deficiency (although increases in dietary iodine, particularly with iodinated salt, have dramatically reduced the frequency of goiters in the United States) ^[16]

• Goitrogens (foods such as cabbage, turnips, peanuts, and soybeans and drugs such as lithium, propylthiouracil, and amiodarone) ^{[17, 18]}

• Heredity ^{[19, 20]}

• Malignancy (with risk factors including radiation exposure, family history, multiple endocrine neoplasia type 2a [MEN 2a], and MEN 2b, among others) ^[21]

The incidence of sporadic nontoxic goiter in the United States has been estimated to be approximately 5%. In some developing countries in which iodine deficiency is severe, up to one third of a population can be affected by goiters. Studies of chest radiographic screenings in Australia and the United States suggest substernal goiter may occur in approximately 0.02% of the population. ^{[22, 23]} In one study, mean age at diagnosis was 55.3 +/- 3.58 years, and most cases were found in women (83.3%). ^[70] Substernal thyroidectomy patients have been found more likely to be older, Hispanic or Black, and have Medicare insurance. ^[78] Reportedly, of patients undergoing thyroidectomy, up to 20% can have substernal goiters. ^{[5, 24, 25, 26, 11, 27]} The definition of a substernal goiter is currently not standardized, with great variability at which depth of thyroid extension beyond the thoracic inlet fulfills criteria. ^[71]

Substernal goiters can often remain asymptomatic for many years. ^{[28, 29]} Goiters are sometimes discovered incidentally during neck and chest radiography. ^{[12, 7]} However, the natural expectation of goiters is continued progressive growth, which may result in lower-neck discomfort, a noticeable neck mass, and progressive compression of the trachea, esophagus, and great vessels, thereby causing dyspnea, dysphagia/globus, and neck venous congestion/superior vena cava syndrome, respectively. ^{[3, 26, 6, 30, 12, 70]}

Substernal goiters are often more prominent on one side of the trachea and are thus highly correlated with tracheoesophageal deviation to the opposite side (see image below). ^{[31, 3]}

Independent of laterality, substernal goiters usually extend into the anterosuperior mediastinum. Unilateral extension is the most common finding with equal frequency between right and left-sided extensions. ^[77] With this type of extension, the recurrent laryngeal nerve is not usually displaced from the tracheoesophageal groove. Occasionally, substernal goiters may extend into the posterior mediastinum behind the trachea. Posterior mediastinal thyroid extension may displace the recurrent laryngeal nerve unexpectedly, further complicating surgical excision of the goiter. ^{[14, 31]}

The identification of substernal extension of an enlarged thyroid gland itself is generally an indication for surgery. ^{[1, 2, 32, 33, 9, 3, 34]} Many authors advocate surgical removal of substernal goiters, even when asymptomatic, for the reasons discussed below.

First, substernal goiters are highly likely to continually grow, leading to the development of compressive symptoms (rarely, but possibly, emergent). In addition, such goiters become increasingly difficult to excise with further growth over time.

Second, the risk of a substernal goiter harboring malignancy is 3%-21%. ^{[10, 11, 12, 6, 13, 14, 15]} The risk of postoperative diagnosis of thyroid cancer is increased in patients with substernal multinodular goiters compared to cervical mutinodular goiters. ^[73] Fine-needle aspiration (FNA) biopsy of nodules in larger substernal goiters suffers from the following factors:

• Riskier in the setting of the large-caliber blood vessels of the mediastinum

• Subject to increased sampling error

• Not possible given the barrier of the chest bones

• Unnecessary given the already present indication for removal

Substernal goiters in individuals who are not medically fit to undergo surgery or who decline excision should be evaluated for malignancy. ^[6] Radiologic evaluation (ultrasonography, CT scanning, or MRI) of the lateral and central neck and mediastinal lymph nodes helps to determine the likelihood of metastatic disease (see image below). ^{[35, 36, 37]}

If lymph nodes appear suspicious on preoperative imaging, FNA biopsy or intraoperative biopsy of the lymph nodes is warranted.

The presence of symptoms is another indication for substernal thyroidectomy. Negative thoracic pressure, swallowing, and gravity help direct the growing goiter into the mediastinum. ^[76] Compressive symptoms, as described above, are often enough to motivate a patient to seek attention and possibly request surgery. Although approximately 85% of goiters are euthyroid, a minority cause symptoms related to hyperthyroidism (eg, palpitations, irregular or rapid heart rates, weight loss, increased heat sensitivity, insomnia, nervousness, tremulousness, diarrhea) or even hypothyroidism (eg, fatigue, weight gain, increased cold sensitivity, depression, constipation, brittle hair).

Thyrotoxicity (hyperthyroidism) in goiters may result from an autonomously functioning nodule or may be precipitated by intake of iodides found in certain expectorants or in radiographic contrast media. Hyperthyroidism requires preoperative medical management to avoid thyroid storm perioperatively.

The appearance of a mass in the low anterior neck may motivate a patient enough to request surgical excision for cosmetic reasons (see image below). ^[38]

Rarely, the Pemberton sign (raising hands induces facial flushing, dilated neck veins, and even stridor from compressive effects of goiter) is an indication for a substernal thyroidectomy.

Surgical intervention is most often the appropriate treatment for substernal goiter. In cases of apparently benign thyroid disease, the surgery should include the removal of the substernal component and other thyroid tissue responsible for obstructive symptoms. Thus, when possible, surgery can be limited to the removal of a single lobe and the isthmus. ^[14]

Recurrence and extension beyond the carina were found to be main risk factors associated with postoperative complications. ^[80] The risk of complications is reduced when injury of the contralateral recurrent laryngeal nerve and parathyroid glands is avoided. In cases of bilateral compression or malignant disease, total thyroidectomy should be performed, particularly in tumors larger than 2 cm in which postoperative radioactive iodine treatment may be used. ^[21]

Close observation may be appropriate for substernal goiters that are small, without symptoms, without radiographic evidence of visceral or vascular compromise, and/or when found in a patient of advanced age or at high surgical risk. Surgeons and medical physicians, in cooperation with the patient, must weigh the risks of surgery and general anesthesia with the presence of symptoms or the possible impending dangers of mass effect of a substernal goiter.

Suppressive therapy (using exogenous thyroid hormone to suppress the pituitary secretion of thyroid-stimulating hormone and its stimulatory effects on thyroid gland growth) is generally ineffective in the management of substernal goiters. Suppressive therapy can be considered when surgical excision is contraindicated but likely would not be very effective. ^{[2, 1, 39, 34, 40]}

Radioactive iodine therapy may be useful in the treatment of hyperthyroidism associated with goiters, but not in the reduction of compressive symptoms. ^[41]

Procedure Planning

Physical examination

Along with a full neck examination, the physical examination (see image below) should include an assessment for the Chvostek sign (found in 10% of cases at baseline when eucalcemic) to determine if this reflex may be used to assess possible postoperative hypocalcemia.

A preoperative vocal cord examination can help determine the baseline condition and laryngeal function (see image below). ^[14] Patients with substernal goiters have been found to exhibit signs of laryngopharyngeal reflux at preoperative laryngoscopy. ^[81]

Blood tests

The following blood tests can be helpful preoperatively:

• Thyroid-stimulating hormone (TSH)

• Free thyroxine (FT4)

• Calcium

• Albumin

• Parathyroid hormone (PTH)

TSH and FT4 are used to assess thyroid hormone production and the need for preoperative treatment of hyperthyroidism or thyroid hormone replacement in cases of hypothyroidism. Calcium, with albumin correction, and PTH can help predict the need for calcium (and vitamin D) replacement after thyroidectomy.

Imaging studies

When the presence and degree to which a goiter has substernal extension is unknown, CT scanning or MRI of the neck and chest can help assess both the need for surgery and preoperative planning. ^{[42, 12]} For example, one study shows that a CT-determined thyroid volume of ≥162 cm3 extending below the thoracic outlet was indicative for an extra-cervical approach. ^[79]

If CT scanning is performed, a scan without contrast is recommended by many. The iodine contained in contrast agents can reduce the uptake and efficacy of postoperative radioactive iodine used in addition to thyroidectomy for the treatment of thyroid malignancy. Iodinated contrast can reduce the efficacy of radioactive iodine for up to 6 months.

Ultrasonography is often an integral and recommended component of thyroid evaluation because of its detailed imagery, potential for directed biopsies, minimal risk profile, and lower cost. However, ultrasonography is not capable of visualizing substernal components of the thyroid gland because the bones of the chest (clavicles, ribs, manubrium, sternum) block the transmission of acoustic information.

Chest radiography and iodine-123 (I123) nuclear medicine scans can show a substernal goiter, but without much anatomic detail of the gland or the surrounding structures.

Barium esophagraphy may show indentation and deviation of the esophagus, suggesting a certain length of substernal goiter causing mass effect. However, the usefulness of esophagraphy is limited given its inability to accurately confirm a thyroid mass because of poor anatomic detail.

Complication Prevention

Overall, complications of substernal thyroidectomy are rare (< 5%). ^{[1, 29, 26, 43]} Effective, safe, and sterile surgical technique is important for minimizing the possible complications of substernal thyroidectomy (bleeding, hematoma, infection, hypoparathyroidism/hypocalcemia, injury to the external branch of the superior laryngeal nerve, and/or recurrent laryngeal nerve injury) and midline sternotomy (hematoma, seroma, mediastinitis/abscess/osteomyelitis, chest bone fracture, sternum shift/disfigurement or dehiscence, pneumothorax/pneumomediastinum). ^[5] Appropriate use of a midline sternotomy by a surgeon trained to do so is important. Indications for a midline sternotomy include ectopic thyroid tissue in the mediastinum, extension of goiter below the aortic arch, and large thyroid tissue extending towards the tracheal bifurcation. ^[72]

Prediction, identification, and treatment of postoperative hypoparathyroidism and hypocalcemia are important for the safety of the patient.

Physicians should educate patients concerning the need (or possible need in the case of thyroid lobectomy surgery) for daily thyroid hormone supplementation and possible future necessary dose adjustments.

To reduce the risks of continued hyperthyroidism, including the development of perioperative thyroid storm (acute, life-threatening elevations of thyroid hormone levels), surgeons, primary care physicians, internists, endocrinologists, and anesthesiologists should work to identify hyperthyroidism preoperatively, to reduce the hormone effects and production with medications such as beta-blockers and possibly antithyroid thioamides (propylthiouracil and methimazole), and to have medications (beta-blockers, propylthiouracil, sodium iodine, corticosteroids) available during and after the operation to reduce acute effects.

If signs of thyroid storm develop during substernal thyroidectomy, the surgical team should halt the surgical procedure.

The goals of substernal thyroidectomy are as follows:

• Complete excision without surgical complications

• An incision and resulting scar as small and as safe as possible

• Resolution of symptoms and/or hyperthyroidism

• Cosmetic improvement with removal of low anterior neck mass

• Determination of the presence of malignancy

Potential complications of substernal thyroidectomy

Injury to the recurrent laryngeal nerve due to thyroidectomy has a reported incidence in the literature of 1%-5% for temporary paralysis and 2% or lower for permanent paralysis. ^{[44, 45, 46, 47, 48, 49]} In some studies, risk of injury to the recurrent laryngeal nerve was not increased in operations with sternotomy. ^[74]

Injury to the external branch of the superior laryngeal nerve due to thyroidectomy has a reported incidence in the literature of 0%-20% (mostly 5%-10%) for temporary paralysis and 5% or lower for permanent paralysis. ^{[50, 49, 51, 52]}

Postoperative hypoparathyroidism due to total thyroidectomy (not in cases of lobectomy) has a reported incidence in the literature of 0.3%-17.5% for temporary dysfunction and 0%-3.4% for permanent dysfunction. ^{[53, 54, 55, 48, 49]} It is often possible to identify and preserve the parathyroid glands during surgery. ^[75] Risk of hypoparathyroidism in operations with sternotomy have been shown to be the same in operations without sternotomy. ^[74]

Hematoma and infection due to thyroidectomy each has a reported incidence of less than 2%. ^{[54, 45]}

Seroma formation due to thyroidectomy has a reported incidence of 1%-6%. ^{[54, 45]}

Hypothyroidism is an expected outcome of total thyroidectomy. Thyroid lobectomy also has a reported incidence of 18%-50%. ^{[56, 57, 58, 59]} Patients with Hashimoto thyroiditis and/or elevated anti-TPO antibody levels appear to be at an increased risk of hypothyroidism after thyroid lobectomy. ^[60] If lymphocytic infiltration and germinal center formation are found in the lobectomy pathologic specimen, thyroid replacement may become increasingly necessary. ^[61]

Randolph et al (2011) found that bilateral goiters larger than 9 cm in diameter and/or heavier than 40 g (including some substernal goiters) are a risk factor for difficult intubation, recurrent laryngeal nerve injury, and postoperative hypocalcemia. ^[62] The degree of goiter extension was found to be directly related to risk of postoperative dysphonia. ^[82] Others studies corroborate the findings of increased risks of vocal cord dysfunction and hypocalcemia with substernal goiter surgery. ^{[63, 4]} However, Raffaelli et al (2011) found no increased rate of complications with substernal thyroidectomy compared to non–substernal thyroidectomy. ^[5]

With total thyroidectomy for bilateral goiter, the risk of recurrence is virtually zero. ^[64] Thyroid lobectomy and cases in which a thyroid cancer is excised carry the risk of recurrent disease depending on the extent and stage of each disease.