INTRODUCTION — Goiter refers to abnormal growth of the thyroid gland. Patients with longstanding goiters (cervical or substernal) may develop symptoms of obstruction due to progressive compression of the trachea or sudden enlargement (usually accompanied by pain) secondary to hemorrhage into a nodule. The most common obstructive symptom is exertional dyspnea, which is present in 30 to 60 percent of cases, and usually occurs when the tracheal diameter is under 8 mm. Substernal goiter may be detected incidentally on chest radiograph or computed tomography (CT) scan or found because of obstructive symptoms such as dyspnea, wheezing, or cough.
The treatment of obstructive and substernal goiters will be reviewed here. The clinical manifestations and evaluation of goiter and the management of benign nonobstructive goiter are reviewed separately.
●(See "Treatment of nontoxic, nonobstructive goiter".)
●(See "Treatment of toxic adenoma and toxic multinodular goiter".)
●(See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter".)
ANATOMIC RELATIONSHIPS — Enlarging thyroid lobes usually grow outward because of their location in the anterior neck in front of the trachea, covered only by thin muscles, subcutaneous tissue, and skin. In patients with substantial enlargement of one lobe or asymmetric enlargement of both lobes, the trachea, esophagus, or blood vessels may be displaced or, less often, compressed. Bilateral lobar enlargement, especially if the goiter extends posterior to the trachea, may cause either compression or concentric narrowing of the trachea or compression of the esophagus or jugular veins. (See "Surgical anatomy of the thyroid gland".)
With some goiters, there is growth of one or both lobes through the thoracic inlet into the thoracic cavity, which can result in obstruction of any of the structures in the inlet (image 1A-B). Such goiters are referred to as substernal.
GOALS OF THERAPY — Once goiter is detected (on physical exam or incidentally during a radiologic procedure performed for other purposes), an evaluation is performed to assess thyroid function and to identify the underlying cause, presence of obstructive symptoms, and presence of suspicious sonographic features in nodules within the goiter. These factors determine management. (See "Clinical presentation and evaluation of goiter in adults", section on 'Approach to evaluation' and "Clinical presentation and evaluation of goiter in adults", section on 'Goiter with obstructive symptoms or suspected substernal goiter'.)
For patients with obstructive goiter (cervical or substernal), the goal of management is to relieve the obstructive symptoms by resecting or ablating the thyroid gland. For patients with asymptomatic substernal goiter, the goal is to prevent growth and subsequent development of obstructive symptoms.
OUR APPROACH
Obstructive symptoms — Patients with obstructive symptoms from a cervical or substernal goiter require removal or ablation of the thyroid. Once obstructive symptoms are present, there is risk of further thyroid growth and progressive tracheal compression, which in some instances (eg, hemorrhage) may be rapid and fatal. For the treatment of obstructive goiter, we suggest surgery rather than radioiodine (see 'Surgery' below). For patients with obstructive symptoms who are unable or unwilling to go undergo surgery, radioiodine therapy is an alternative option. (See 'Poor operative candidates' below.)
However, the reduction in thyroid volume with radioiodine is only moderate, and there are theoretical concerns that radioiodine could acutely worsen obstruction or a missed malignancy. Most obstructive cervical or substernal goiters are benign. However, patients with nodules within a goiter that are malignant or suspicious for malignancy on fine-needle aspiration (FNA) biopsy require surgery.
Asymptomatic substernal goiter — The main treatment options for patients with asymptomatic substernal goiter are surgery or observation with monitoring. The choice of therapy depends upon the extent of substernal extension and patient characteristics.
The author of this topic and others suggest surgery for most patients with asymptomatic substernal goiters that extend below the level of the brachiocephalic vein, assuming they are good surgical candidates (image 1B) [1-6]. However, this is an area of controversy, and other experts prefer to monitor such patients.
The arguments for removing a substernal goiter in a patient who has no obstructive symptoms include:
●Some goiters continue to enlarge and become more difficult to remove if obstructive symptoms do develop. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)
●Suppressive therapy is relatively ineffective and is associated with significant morbidity in older patients.
●Forty-two percent of patients with evidence of upper airway obstruction on flow-volume loops are asymptomatic [7].
●As patients age, surgical complications are more common and severe [8].
●The substernal component could contain a cancer that cannot be palpated or biopsied (range of reported cancer risk 3 to 22 percent) [6,9].
●There is a small risk of hemorrhage into the goiter that could result in acute airway obstruction. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)
We prefer observation rather than surgery for asymptomatic patients with normal flow-volume loops whose goiters end at the level of the brachiocephalic vein or higher. We monitor such patients with serial computed tomography (CT) scans, initially after one year and, if stable, at increasing intervals (eg, two years later, then three years, then five years). Other asymptomatic patients with substernal goiter who may be followed with serial CT scans, rather than undergo surgery, include the following:
●Older patients who are poor operative candidates.
●Patients without thyroid enlargement whose glands extend slightly substernally due to kyphosis.
●Patients whose goiters extend only slightly substernally on a CT scan obtained without neck extension may not be substernal when the neck is extended. Their glands are also usually accessible for FNA biopsy if indicated.
●Patients who, in retrospect, have serial CT scans showing long-term stability of a substernal goiter, especially if the inferior extent is above the level of the brachiocephalic vein.
However, if growth is detected on serial CT scans, we suggest surgery, if possible, for these patients also. Treatment of patients who are unable or unwilling to undergo surgery is reviewed below. (See 'Poor operative candidates' below.)
Levothyroxine may have a limited role in patients with asymptomatic substernal goiters. In a randomized trial, thyroid-stimulating hormone (TSH)-suppressive doses of levothyroxine reduced goiter size in approximately two-thirds of patients with sporadic, multinodular goiters [10]. However, most large goiters do not shrink sufficiently to alleviate symptoms [11], any reduction in size is not rapid, and levothyroxine is not effective in those patients who already have low serum TSH concentrations (ie, subclinical hyperthyroidism). Additionally, growth of the goiter may resume as soon as levothyroxine treatment is stopped.
SURGERY — For the treatment of obstructive goiter, we suggest surgery rather than radioiodine. In addition, patients with nodules within a goiter that are malignant or suspicious for malignancy on fine-needle aspiration (FNA) biopsy require surgery. The author of this topic and others also suggest surgery for most patients with asymptomatic, substernal goiters that extend below the level of the brachiocephalic vein, assuming they are good surgical candidates [1-6]. Patients with substernal goiter should be referred to an experienced thyroid surgeon as complication rates appear to be lower in high-volume centers [12]. Patients who may require sternotomy should be referred to an experienced thoracic surgeon.
Preoperative assessment — The initial evaluation of substernal goiter is discussed in detail separately and includes serum TSH to evaluate for subclinical or overt hyperthyroidism, imaging studies (noncontrast computed tomography [CT] or magnetic resonance imaging [MRI]) to evaluate the extent of the goiter and its effect upon surrounding structures, a flow-volume loop study if there is uncertainty if the goiter is causing upper airway obstruction, and FNA biopsy if malignancy is suspected. (See "Clinical presentation and evaluation of goiter in adults", section on 'Goiter with obstructive symptoms or suspected substernal goiter'.)
The decision to proceed with surgery is usually made on the basis of symptoms, anatomic studies, and the results of a flow-volume loop study. Most nodules within goiters have benign thyroid aspirates.
Once the decision to proceed with surgery has been made, other preoperative assessment of substernal goiter should include laryngoscopy to assess the tracheal lumen and vocal cord function. If the patient is hyperthyroid and surgery is elective, an antithyroid drug and, if not contraindicated, a beta blocker should be given for several weeks before surgery (see "Surgical management of hyperthyroidism", section on 'Preoperative preparation'). Patients with subclinical hyperthyroidism do not need to be prepared with an antithyroid drug.
Surgical approach — The majority of obstructive and substernal goiters can be excised through a standard cervical incision, while partial or complete sternotomy or even thoracotomy may be required in patients with previous cervical thyroidectomy, very large substernal goiters, or invasive cancer [13-15]. In an Italian study of 19,662 patients undergoing total thyroidectomy at six centers, 1055 had substernal goiters and only 69 (6.5 percent) required sternotomy [16]. Patients requiring sternotomy were more likely to have a malignancy: 36 percent compared with 22 percent of those excised through a cervical incision. Similar results were noted in two single-center studies [6,17] and in a systematic review [9]; recurrent or ectopic goiter in addition to malignancy were associated with the need for sternotomy.
The extent of surgery for benign goiter depends upon the expertise of the surgeon, the extent of the goiter, and whether the patient has obstructive symptoms and signs. Because of the risk of recurrent goiter, a total or near-total thyroidectomy should be performed unless during the procedure the surgeon feels that a less extensive operation is prudent because of an increased risk of recurrent laryngeal nerve injury or hypoparathyroidism due to anatomic considerations. If a more limited operation is done, we suggest:
●Patients with large, relatively symmetric goiters should have a bilateral subtotal thyroidectomy.
●Patients with asymmetric goiters should have a hemithyroidectomy on the more involved side and a subtotal thyroidectomy on the contralateral side. If the patient already has vocal cord paralysis on the one side and the contralateral thyroid lobe is not very large, we suggest doing only a hemithyroidectomy and isthmusectomy.
In patients with chronic autoimmune thyroiditis who have concentric tracheal compression, excision of the isthmus alone may be sufficient to alleviate the compression. These fibrous glands may be difficult to dissect free from nerves and parathyroid glands, and more extensive surgery may result in complications.
Complications — The major complications of surgery for large goiters and substernal goiters are injury to the recurrent laryngeal nerves, trachea, and parathyroid glands [1-4,6,13,15,18].
Surgery for substernal goiter appears to be associated with higher complication rates than surgery for cervical goiter [8,19], as illustrated by a statewide database of cervical (n = 32,777) and substernal thyroidectomies (n = 1153) performed between 1998 and 2004. Patients who underwent substernal thyroidectomy were more likely to be older, have a comorbid condition, be uninsured, be undergoing total thyroidectomy, and have surgery at a low-volume center [8]. After adjusting for these variables, patients undergoing substernal thyroidectomy were still at higher risk for the following:
●Recurrent laryngeal nerve injury (odds ratio [OR] 2.4, 95% CI 1.5-3.8)
●Postoperative bleeding (OR 1.9, 95% CI 1.2-2.9)
●Deep venous thrombosis (OR 5.9, 95% CI 2.4-15.2)
●Respiratory failure (OR 4.2, 95% CI 2.8-6.2)
●Red blood cell transfusion (OR 5.7, 95% CI 3.8-8.5)
●Mortality (OR 8.3, 95% CI 4.2-16.3)
In the same database, complication rates were significantly lower at hospitals that performed a high volume of substernal thyroidectomies [12].
Of note, this study did not report how many patients with substernal goiter required sternotomy, a procedure that may be associated with higher surgical complication rates [16,20]. In the Italian study of 1055 patients with substernal goiter, 69 patients who required a sternotomy were compared with 986 patients whose goiters were excised through a cervical incision [16]; only phrenic nerve palsy was more common in the sternotomy group. In a study from the National Surgical Quality Improvement Program database of 2716 patients with substernal goiter, the 14 percent who required a sternal split or transthoracic approach had a higher incidence of unplanned intubation (OR 2.70, 95% CI 1.17-6.25) and bleeding (OR 5.56, 95% CI 2.38-13.0); a higher incidence of death (1.9 versus 0.3 percent) was not statistically significant [20]. Together, these studies suggest that surgery for substernal goiter (using a cervical approach or sternotomy) is associated with higher complication rates than surgery for cervical goiter.
Recurrent laryngeal nerve injury — Transient recurrent laryngeal nerve injury has been reported to occur in 2 to 9 percent of patients undergoing surgery for substernal goiter [6,13,14,18]. Permanent nerve injury occurs less commonly: 0 and 0.03 percent in the two largest studies [6,18] and 3 percent in two other reports [13,14]. Patients with bilateral nerve injury and therefore bilateral vocal cord paralysis require tracheostomy to provide an adequate airway.
Hypocalcemia — Hypocalcemia due to hypoparathyroidism is the most frequent complication of near-total thyroidectomy and is more common when the goiter is extensive and anatomic landmarks are displaced and obscured. Hypocalcemia may be transient or permanent. Transient hypoparathyroidism occurred in 12 of 170 patients (7 percent) in one series [6].
Current requirements for short hospital stays argue for early treatment of hypocalcemia. Our approach to the management of hypocalcemia is summarized in the table and reviewed in detail separately (table 1). (See "Differentiated thyroid cancer: Surgical treatment", section on 'Hypoparathyroidism' and "Hypoparathyroidism", section on 'Postsurgical hypoparathyroidism'.)
Tracheomalacia — In patients who have tracheomalacia due to pressure-induced destruction of tracheal rings by the goiter, the airway may collapse during the postoperative period. In one study, 10 percent of patients could not be immediately extubated, although all were successfully extubated by 10 days [21]. These patients were older, had larger goiters, and were more likely to have tracheal compression. If recognized at the time of surgery, tracheomalacia may in some cases be treated by partial tracheal resection and reconstruction; otherwise, tracheostomy is necessary.
In a systematic review, the presence of a substernal goiter for more than five years causing tracheal compression was a risk factor for tracheomalacia and tracheostomy. However, in this review, tracheomalacia was an infrequent occurrence (3 percent) and was managed without tracheostomy in approximately 50 percent of cases [9].
Levothyroxine after surgery — Patients who undergo total thyroidectomy for benign disease should start a replacement dose of levothyroxine daily at an approximate dose of 1.6 mcg/kg body weight. Patients over 65 years should be started at a 10 to 15 percent lower dose. Serum TSH should be tested approximately six weeks after starting the replacement therapy. The TSH should be kept in a normal range. (See "Treatment of primary hypothyroidism in adults".)
Treatment with higher doses of levothyroxine to suppress serum TSH to prevent goiter recurrence in patients who have already had surgery for obstructive goiter (versus no thyroid hormone therapy or replacement therapy if needed to normalize the serum TSH concentration) is controversial. In one study with 10 years of follow-up, the recurrence rate was lower in the patients treated with levothyroxine (5 versus 42 percent in the untreated group had recurrent goiter) [22]. However, this benefit was not confirmed in a report with 30 years of follow-up; the recurrence rates were similar (41 and 45 percent) in treated and untreated patients [23]. (See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter".)
We generally do not prescribe postoperative TSH suppressive therapy with levothyroxine. However, the author of this topic suggests a trial of suppressive therapy in young patients with no contraindications to TSH suppression who experience growth of a surgical remnant.
POOR OPERATIVE CANDIDATES — For patients with obstructive symptoms who are unable or unwilling to undergo surgery, radioiodine therapy is an alternative option.
Radioiodine therapy — Radioiodine is a reasonable option for patients who cannot or do not want to undergo surgery, particularly if the substernal or obstructive goitrous tissue is functional on thyroid radionuclide imaging. In patients with nonobstructive multinodular goiter, radioiodine therapy results in goiter volume reductions in the range of 30 to 60 percent. Pretreatment with recombinant human thyroid-stimulating hormone (rhTSH, thyrotropin alfa) allows treatment with lower doses of radioiodine for thyroid volume reduction but may result in development of mild hyperthyroidism and transient goiter enlargement, or rarely induce Graves' disease. Methimazole may also be used to increase the radioiodine uptake and reduce the dose needed to reduce thyroid volume. (See "Treatment of nontoxic, nonobstructive goiter", section on 'Radioiodine therapy'.)
Results of radioiodine therapy for obstructive goiter include the following:
●In one series of 14 patients with large multinodular goiters, eight of whom had respiratory symptoms and eight of whom had substernal extension, all improved after treatment with 200 to 400 microcuries/g of radioiodine, and no patient had an acute exacerbation of obstructive symptoms [24].
●Similar improvements in obstructive symptoms were seen in a series of 19 older patients treated with 100 microcuries/g tissue (average total dose 70 millicuries). Goiter volume decreased by 40 percent [25].
●Volume reduction of the cervical and substernal components is similar (30 percent in one study) [26].
Despite the reasonable results with radioiodine, surgery is still the treatment of choice because of concerns that radiation thyroiditis might result in worsening of airway obstruction and the need to rule out the diagnosis of carcinoma if the goiter is mostly substernal. However, for patients with obstructive symptoms who are not surgical candidates, we suggest radioiodine therapy as an alternative approach.
Recombinant human TSH — Similar to results seen with smaller multinodular goiters, the addition of rhTSH to radioiodine in patients with obstructive goiters results in a greater reduction in thyroid volume than radioiodine alone. However, rhTSH is not currently US Food and Drug Administration (FDA) approved for this indication, and we do not recommend it, pending additional clinical trials demonstrating safety and efficacy. This is discussed in detail separately. (See "Treatment of nontoxic, nonobstructive goiter", section on 'Pretreatment with recombinant human TSH to increase the radioiodine uptake'.)
Methimazole — Pretreatment of nontoxic nodular goiter with methimazole has also been used to increase the radioiodine uptake and reduce radioiodine dose or frequency of repeat radioiodine treatment [27]. This is not currently an FDA-approved indication for this drug, but unlike rhTSH, it does not cause hyperthyroidism (it might cause transient hypothyroidism), and this author does use methimazole to increase the radioiodine uptake in select patients with low radioiodine uptake who prefer radioiodine over surgery or who are poor surgical candidates.
SUMMARY AND RECOMMENDATIONS
●The most common symptom in patients with obstructive cervical or substernal goiter is exertional dyspnea, which is present in 30 to 60 percent of cases. This symptom usually occurs when the tracheal diameter is under 8 mm. (See 'Introduction' above and "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)
●Bilateral thyroid lobe enlargement, especially if the goiter extends posterior to the trachea, may cause either compression or concentric narrowing of the trachea or compression of the esophagus or jugular veins. With some goiters, there is growth of one or both lobes through the thoracic inlet into the thoracic cavity, which can result in obstruction of any of the structures in the inlet. Such goiters are referred to as substernal (image 1A-B). (See 'Anatomic relationships' above.)
●Patients with obstructive symptoms from a cervical or substernal goiter require removal or ablation of the thyroid. (See 'Obstructive symptoms' above.)
●For patients with obstructive goiter, we suggest surgery rather than radioiodine (Grade 2C). The reduction in thyroid volume with radioiodine is only moderate, and there are theoretical concerns that radioiodine could acutely worsen obstruction or a missed malignancy. However, radioiodine therapy is an option for patients with obstructive symptoms who are poor surgical candidates. (See 'Surgery' above and 'Radioiodine therapy' above.)
●For asymptomatic patients with normal flow-volume loops whose goiters end at the level of the brachiocephalic vein or higher, we suggest observation rather than surgery (Grade 2C). We monitor such patients with serial computed tomography (CT) scans, initially after one year and, if stable, at increasing intervals (eg, two years later, then three years, then five years). (See 'Asymptomatic substernal goiter' above.)
Recommendations for asymptomatic patients with goiters that extend below the level of the brachiocephalic vein are controversial. The author of this topic suggests surgical excision for most patients except older patients and those who are poor operative candidates, while other experts suggest observation of asymptomatic patients. All patients requiring surgery for substernal goiter should be referred to experienced thyroid surgeons in high-volume centers to minimize complication rates. (See 'Surgery' above.)
●For most patients undergoing surgery, we suggest a total or near-total thyroidectomy, rather than subtotal thyroidectomy, to minimize the risk of recurrent goiter (Grade 2C). (See 'Surgical approach' above.)
●Patients who undergo total thyroidectomy for benign disease should start a replacement dose of levothyroxine daily at an approximate dose of 1.6 mcg/kg body weight. Patients over 65 years should be started at a 10 to 15 percent lower dose. We typically do not prescribe suppressive doses of levothyroxine to prevent recurrence. However, the author of this topic suggests a trial of suppressive therapy in young patients with no contraindications to suppression who experience growth of a surgical remnant. (See 'Levothyroxine after surgery' above.)
