Substernal Goiter

Etiology

The etiology of substernal goiter is the same as cervical goiter. Descent of cervical goiter through the thoracic inlet is considered to be the cause, because substernal goiters get their blood supply from the neck, mainly from the inferior thyroid artery. Ectopic thyroid tissue in the chest causing de novo substernal goiter is rare, accounting for only 2% of all substernal goiters.[1] Sometimes cervical goiters that descend to the thoracic cavity lose their continuity with thyroid tissue in the neck and seem like isolated occurrences in the chest. A substernal goiter may be connected to a cervical goiter with only a fascial extension.

Epidemiology

The prevalence of substernal goiter in the general population is unknown because of a lack of epidemiological studies. Because of the widespread use of imaging, more cases of substernal goiter are expected to come to clinical attention. Substernal goiter is more commonly diagnosed after age 50 years and is four times more common in females.[2][3] A recent surgical series reported the rate of substernal goiter as 7% among patients who underwent thyroid surgery.[4]

History and Physical

Patients are often completely asymptomatic, and a chest X-ray, CT, or MRI may incidentally detect substernal goiter. Symptoms are typically mechanical/compressive in nature, and clinical manifestations due to hypo or hyperthyroidism can also be present. The patient may complain of local obstructive or compressive symptoms. The most common obstructive symptom is exertional dyspnea, followed by choking sensation, cough, and stridor. As patients with substernal goiter are usually in their sixth decade or later, the etiology of dyspnea must accurately be determined because other comorbidities common in the elderly, like chronic obstructive pulmonary disease (COPD), asthma, or congestive heart failure can also cause dyspnea.[5] Other symptoms may include difficulty in swallowing due to esophageal compression, hoarseness due to recurrent laryngeal nerve compression, prominent jugular veins, or superior vena cava syndrome due to compression of venous structures. As goiter grows slowly, the condition can be asymptomatic or insidious. Enlargement of thyroid tissue at the thoracic inlet or in the chest cavity is the cause of obstructive symptoms. These anatomical areas have confinements and are unable to accommodate the enlarging goiter.

Hyperthyroidism and hypothyroidism may coexist with substernal goiter and may have their respective signs. The enlarged cervical component of the substernal goiter may be visible or palpable. If there is compression of the trachea, stridor might be audible. Stridor refers to obstruction of the airway outside the chest cavity, producing a high-pitched sound heard more on inspiration. This differs from wheezing, which is an obstruction of the lower respiratory tract that causes a continuous whistling sound heard more during expiration.

Pemberton sign may be sought during physical examination. The patient is asked to raise both arms until medial parts touch to lateral sides of the head for at least a minute. The development of facial congestion, bulging of neck veins, hoarseness or dyspnea indicates a positive Pemberton sign, indicating compression at the thoracic inlet. Arm elevation spirometry with flow volume loops has been suggested to increase the sensitivity to detect upper airway obstruction and also as an objective assessment of the Pemberton sign.[6] “Corking” of the thyroid at the thoracic inlet is believed to cause compression of surrounding anatomical structures and a positive Pemberton sign. A cork effect is the result of either goiter descending into the thoracic cavity or thoracic inlet elevation towards the neck. Corking may cause symptoms if the patient with substernal goiter flexes or hyperflexes his/her head. MR angiography of a patient with a positive Pemberton sign showed that clavicles moved and compressed external and internal jugular veins at the subclavian vein confluence against the enlarged thyroid rather than a “cork effect” and resembled a nutcracker, the explanation being medial clavicular heads compressing venous structures against enlarged thyroid within the narrowed thoracic inlet.[7]

Evaluation

TSH level needs to be measured. Total or free T4, total or free T3 can be obtained if TSH is abnormal. Alternatively, free T4, free T3, and TSH can be measured at once to assess thyroid hormone status. At the initial evaluation, some healthcare professionals also obtain anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies to assess for Hashimoto’s thyroiditis, which may coexist with substernal goiter.

A thyroid ultrasound is recommended to assess the cervical component of the goiter. Thyroid ultrasound cannot assess the extent and characteristics of the intrathoracic portion of the substernal goiter, because ultrasound waves cannot penetrate bone and do not propagate well through the air in the lungs.

Chest X-ray may show an upper mediastinal mass and tracheal deviation and/or compression.

The preferred imaging modality is computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. They accurately assess the size and extent of substernal goiter and its relationship with other anatomic structures. Iodinated contrast use for CT scanning can induce hyperthyroidism and precludes nuclear medicine thyroid scan until iodine load is cleared from the body. Nuclear medicine thyroid (iodine or technetium) scan may show thyroid tissue in the thoracic cavity. The absence of uptake may indicate a cold nodule in the mediastinum and does not rule out substernal goiter.

Barium esophagography or upper endoscopy can be considered if the predominant symptom is dysphagia, but none of them are routine.

The most important and recommended imaging modality is CT of the chest. CT allows for characterization of the thyroid mass, its size, morphology, anatomic relationship with surrounding structures, enables detection of tracheal deviation, and quantification of tracheal compression. If the tracheal dimension is 10 mm or less, surgical intervention is required.

A pulmonary function test with a flow-volume loop study is required. Even if the patient has no symptoms, pulmonary function tests may be abnormal. Substernal goiter may cause a blunted flow-volume loop with an almost equal degree of flow limitation in both inspiration and expiration with flattening of both limbs of the flow-volume loop, indicating a mechanical fixed upper airway obstruction. Pulmonary function tests are helpful to differentiate from other causes of dyspnea, like COPD.

Thyroid cancer has been reported in 0-19% of substernal goiters.[8][5] A recent guideline on surgical management of adult thyroid disease notes the risk of malignancy in substernal goiter as 9% to 13%.[1] Although thyroid fine-needle aspiration is the gold standard for cervical thyroid nodules, it is not recommended for substernal goiters. One of the side effects of thyroid fine-needle aspiration is hemorrhage. Bleeding inside a substernal goiter or a substernal thyroid nodule may cause sudden enlargement and respiratory compromise. Fine needle insertion into the thoracic cavity has the potential to cause pneumothorax. Fine needle aspiration of a substernal goiter or a nodule within a substernal goiter is not recommended.

Treatment / Management

If the patient has hypo or hyperthyroidism, they should be addressed. The treatment of symptomatic substernal goiter is surgery. The management of asymptomatic substernal goiter is controversial with no agreed-upon single approach. If the patient is asymptomatic, absence of a fixed upper airway obstruction or significant compression of the trachea, an expectant observation to monitor for symptoms and signs can be considered. A close watch on any change in the size of the goiter, tracheal diameter, and thyroid functions is necessary in such cases. With this approach, the patient should avoid iodine-containing supplements, iodine-containing multivitamins, iodine-containing medications, and iodinated contrast agents to avoid the development of iodine-induced hyperthyroidism. Expectant monitoring involves periodic thyroid function tests, CT of the chest in one year, and if stable less frequently. If no abnormalities on observed parameters develop, periodic monitoring continues. If there is a growth of substernal goiter, evolving compression of trachea manifesting with a decrease in tracheal size, development of thyroid autonomy with hyperthyroidism, then surgery is the next step. If the patient has hyperthyroidism, an antithyroid drug, and a beta-blocker should be given two weeks before surgery, provided that there are no contraindications to beta-blockers. Also, an inorganic iodine solution should be given 7-10 days before surgery to prevent a thyroid storm. If the patient has only subclinical hyperthyroidism, there is no need to prepare the patient for surgery.

Proponents of surgery for asymptomatic patients worry that substernal goiter will grow and compress intrathoracic structures eventually if left untreated, although there are no studies documenting this process. This will require a longitudinal study, which we do not have for substernal goiter. Another worry is the presence of undiagnosed thyroid cancer within a substernal goiter. As patients age, if surgery performed later rather than earlier, surgery would be more difficult and would have a higher complication rate, and patients may evolve from a lower surgical risk category to a higher one over time.

When tracheal narrowing progresses to 35% or more, surgical intervention has been associated with 95% to 98% resolution of compressive symptoms. Tracheal compression of 35% or more has been advocated as an indication for surgical intervention.[9] 35% reduction was not determined prospectively, but by comparing the narrowest tracheal size with the widest tracheal size on cross-sectional CT imaging.(B2)

Suppressive therapy (to lower TSH levels) with levothyroxine is ineffective. Radioactive iodine therapy has no role, even if the patient has hyperthyroidism. Radioactive iodine treatment can obscure or miss a malignancy. Radiation-induced thyroiditis in the closed chest cavity can theoretically cause respiratory compromise.

The definitive therapy is surgery, preferably total thyroidectomy. The cervical approach is used in the vast majority. A recent study reported that 78.3% of patients had a total thyroidectomy, 18.3% subtotal thyroidectomy, and 3.3% lobectomy.[2] Definitive Surgical Management of Thyroid Disease in Adults Guidelines recommend total thyroidectomy for bilateral goiter as a principle, but there are some clinical scenarios that total thyroidectomy may not be feasible or possible.[1] Patients require an extra-cervical approach in 1% to 7.6% of the surgeries.[4][5][10] The extra-cervical approach may range from partial sternotomy to thoracotomy. As substernal goiter surgery is challenging, it should be performed in a referral center.[4] In a recent study, 17% of patients with substernal surgery required an extra-cervical approach showing that the rate is highly variable among institutions.[3](B2)

Mercante and coworkers proposed a classification system for substernal goiter.[11] Grade I, if the lower border of the thyroid is above the aortic arch, Grade II if the lower border of the thyroid is between the convex and concave parts of the aortic arch, and grade III if the lower border of the thyroid is below the concave part of the aortic arch. The need for an extra-cervical approach was significantly higher for grade II and III goiters. Indications for sternotomy are an extension of goiter to the level or below the aortic arch, a dumbbell-shaped goiter, an iceberg shaped goiter with more than 70% of thyroid volume in the mediastinum, location in the posterior mediastinum, recurrent goiter, ectopic source of substernal goiter with blood supply from the mediastinal vessels rather than inferior thyroid artery, thyroid cancer with the possibility of invading mediastinal structures.[12][3](B2)

Surgery for substernal goiter is associated with more complications than surgery for cervical goiter.[8] A recent study reported complications of substernal goiter surgery: postoperative bleeding (0.5%), permanent unilateral recurrent laryngeal nerve palsy (1.3%), bilateral recurrent laryngeal nerve palsy (0.6%), transient hypoparathyroidism (14%), and permanent hypoparathyroidism (4.1%).[10] The mortality rate of substernal goiter surgery has been reported as high as 2.3% [8].(B2)

Depending on the patient’s symptoms, signs, clinical, laboratory, and radiologic features, and surgical risk, a clinical decision should be made for expectant observation versus surgical intervention in asymptomatic patients. Surgery is required for symptomatic patients who have compression of intrathoracic vital structures. Patients with a positive Pemberton sign require surgery.[1]

After thyroidectomy, levothyroxine replacement at a dose of 1.6 mcg/kg body weight for all patients and lower and gradually increasing doses for elderly or cardiac patients should be started.

Differential Diagnosis

• Thymoma and thymic carcinoma
• Bronchogenic cyst
• Lymphoma
• Teratoma and germ cell tumors
• Pericardial cyst
• Ganglioneuromas and other neurogenic tumors of the posterior mediastinum

Prognosis

There are no studies on the natural history of substernal goiter. No prospective studies are available that compare expectant monitoring with surgery. The concept of substernal goiter to enlarge and eventually cause symptoms and severe respiratory distress if left untreated has not been shown in any prospective study.[8]

Complications

• Substernal goiter can compromise trachea, venous vasculature, and other surrounding intrathoracic anatomical structures.
• Substernal goiter may cause life-threatening respiratory compromise if there is sudden enlargement. Hemorrhage into substernal goiter may cause acute enlargement of thyroid tissue and airway compression. An upper respiratory tract infection may increase the symptoms of upper airway obstruction.
• Thyroid cancer: A study reported that 72% of papillary thyroid cancer foci were intrathoracic, and 28% were cervical in patients operated for substernal goiter. When evaluated based on per nodule rather than per subject in statistical analysis, incidental foci of papillary carcinoma was significantly more common in substernal goiter than cervical goiter (31 versus 19%, p<0.01)[5]
• Phrenic nerve paralysis
• Horner syndrome due to compression of the cervical sympathetic chain
• Jugular vein thrombosis
• Cerebrovascular steal syndrome
• Superior vena cava syndrome