Substernal multinodular goiter resulting in superior vena cava syndrome and tracheal compression

Abstract

A woman in her early 70s presented to the family medicine clinic with shortness of breath and an inability to lie flat for several months. When lying flat or on lifting her arms above her head, her face would turn bright red and she felt lightheaded. The patient also had hair loss and skin colour changes of the upper extremities. On examination, the thyroid was palpated and felt normal without enlargement or nodularity. Considering the patient’s 70–90 pack-year smoking history, a malignant process of the lung causing superior vena cava syndrome was suspected. CT chest with intravenous contrast revealed a markedly enlarged thyroid with substernal extension of a multinodular goitre producing a mass effect in the upper mediastinum. Thyroid-stimulating hormone was normal. The patient had a total thyroidectomy performed by endocrine surgery. Pathology revealed multinodular hyperplasia and chronic lymphocytic thyroiditis. The patient recovered well postoperatively and her compressive symptoms resolved.

Background

A broad differential diagnosis is essential to effective patient care as often a disease process may be missed if it is not actively searched for. This case report describes the discovery of a benign process causing a rare syndrome in spite of a clinical history and physical examination suggestive of a malignant process.

Superior vena cava (SVC) syndrome results from the obstruction of major veins draining into the right atrium of the heart.¹ SVC presents clinically as oedema, flushed skin of the face and upper extremities, increase in neck size, headache, hoarseness, stridor, stupor, and respiratory distress. These symptoms worsen on bending forward or lying supine.² SVC is a thin-walled vessel in a tight compartment, making it a target for obstruction by intrathoracic space-occupying lesions. Historically, SVC syndrome has been linked to malignancy, most notably carcinoma of the lung.³ Small cell and non-small cell carcinoma of the apical lung account for a vast majority of SVC syndrome, while benign intrathoracic lesions present in fewer cases.² Of these intrathoracic lesions, substernal multinodular goitres of the thyroid are rarely implicated as a cause of SVC syndrome.^{4 5} The definition of a substernal goitre has been debated in the literature, but the most agreed-on definition is a goitre in which the greater mass is inferior to the thoracic inlet.^{4 6} Substernal goitres tend to grow slowly over many years and become symptomatic only when large.⁷ A symptomatic patient is most likely to experience airway compression and dysphagia, but rarely SVC syndrome.⁸

We report the case of a large substernal multinodular goitre causing both SVC syndrome and tracheal compression in a patient with multiple risk factors for primary lung carcinoma. Additionally, this patient had a normal thyroid-stimulating hormone (TSH) and normal thyroid examination with no palpable nodules or enlargement. This case demonstrates the need to perform a thorough history and physical examination while considering a broad differential diagnosis. Multinodular goitres are commonly implicated in iodine-deficient regions of the world due to resultant hypothyroidism stimulating thyroid growth. However, in the iodine-rich United States, the most common causes of multinodular goitres are Hashimoto’s thyroiditis, Graves’ disease, or other unknown genetic influences.⁹

Case presentation

A woman in her early 70s presented to the family medicine clinic with worsening shortness of breath for the past several months. She had a medical history of congestive heart failure, coronary artery disease, atrial fibrillation with an implanted pacemaker, mitral regurgitation, bicuspid aortic valve, pulmonary hypertension, cerebral infarction and type II diabetes. Additionally, she had a 70–90 pack-year smoking history with pulmonary function testing showing mild chronic obstructive pulmonary disease.

Prior to presentation, the patient reported experiencing worsening shortness of breath with activity and lying flat. These symptoms caused her to skip cardiology appointments and imaging studies. The patient described that when she would lie flat or raise her arms above her head, she felt lightheaded with symptoms of shortness of breath and facial flushing. She also described hair loss, a bad taste in her mouth and skin colour changes on her upper extremities. She denied chest pain, palpitations, continuous lightheadedness and dizziness. The patient believed these symptoms were occurring due to her recent initiation of amiodarone HCL 200 mg daily for atrial fibrillation about 1 year prior to onset of symptoms.

On examination, the patient was morbidly obese with a BMI of 42.62 kg/m². She had a blood pressure of 101/67 mm Hg, pulse of 67 beats per minute and temperature of 37.2°C. The patient appeared drowsy but in no apparent distress. Her neck was supple, and the thyroid was normal without enlargement or nodules on palpation. The patient was snoring and gasping frequently during the physical exam, but her lungs were clear of wheezing or crackles. Her heart had an irregular rhythm with a soft murmur. When asked to raise both arms above her head, her face immediately flushed and started to swell, causing the patient to feel lightheaded. The upper extremity veins were dilated, and nummular eczema was noted on the arms. The remainder of the physical exam was normal.

Investigations

Given the patient’s symptoms, SVC syndrome was suspected. Considering the patient’s extensive smoking history, a CT chest with intravenous contrast was ordered to evaluate for potential carcinoma of the lung compressing the SVC. Additionally, labs were drawn, including haemoglobin A1C, lipid panel, complete blood count, comprehensive metabolic panel, TSH, and a microalbumin-creatinine ratio. All labs were found to be within normal reference ranges, including a TSH of 2.203 uIU/mL (0.300–4.000 uIU/mL). Further, thyroid laboratory testing was not ordered due to the normal TSH.

One month after her initial visit, the patient returned for follow-up. She did not set up the CT scan with intravenous contrast due to discomfort when lying down. She met with her cardiologist prior to this visit and began weaning amiodarone with the goal of eventual total discontinuation. The patient reported she was feeling slightly better except for shortness of breath. On examination, she had dilated superficial neck and upper extremity veins with mild jugular venous distension. The remainder of the exam was unchanged from the previous visit. The patient was reassured and encouraged to follow through with a chest CT, to which she responded positively.

Chest CT with intravenous contrast was performed shortly after her second visit, which showed a markedly enlarged thyroid with substernal extension of a multinodular goitre producing a mass effect in the upper mediastinum (figure 1). The thyroid was compressing the SVC superior to the brachiocephalic vein junction causing right lateral deviation and a small calibre. SVC distal to the brachiocephalic vein junction was patent. The thyroid was also compressing the proximal portion of the trachea, causing narrowing and slight leftward deviation. No hilar adenopathy or pulmonary mass lesions were identified. The patient had never been told she had thyromegaly or goitre prior to imaging. Thyroid dysfunction had never been suspected in this patient, as she lacked obvious risk factors for multinodular goitre, such as iodine deficiency. The patient was referred to a endocrine surgeon for a potential thyroidectomy consult.

Figure 1.

CT showing a markedly enlarged thyroid with prominent substernal extension of the right lobe causing narrowing and leftward deviation of the proximal trachea.

Endocrine surgery performed an ultrasound, which showed an irregular thyroid gland. The isthmus measured 0.42 cm, right lobe measured 9.39 × 3.85 × 4.18 cm, and left lobe measured 10 × 2.89 × 4.03 cm (figure 2). Of note, the whole extent of the gland could not be appreciated due to its large size. Despite the large size of the thyroid, no thyromegaly or nodularity had been appreciated on physical examination, consistent with the normal thyroid exam performed by the patient’s primary care physician initially. This finding was believed to be due to the growth of thyroid gland being completely substernal. Total thyroidectomy was recommended to relieve compressive symptoms.

Figure 2.

Right and left lobes post-total thyroidectomy.

Differential diagnosis

On top of the differential diagnosis for the patient’s clinically apparent SVC syndrome was lung carcinoma, such as a Pancoast tumour, due to the patient’s extensive smoking history. The differential also included worsening cardiovascular or pulmonary disease, causing the patient’s severe dyspnoea, but this would not explain the apparent compressive symptoms.

Initially, thyroid pathology was low on the differential due to the patient’s normal thyroid exam and lack of endocrine symptoms suggesting hyperthyroidism or hypothyroidism. On visualisation of the large multinodular goitre, the top of the differential included subclinical Hashimoto’s thyroiditis due to the patient’s laboratory values and symptoms. Multinodular goitre due to iodine deficiency is one of the most common causes worldwide, but this patient had never lived outside of the United States.⁹ Although this patient had been taking amiodarone, which is implicated in amiodarone-induced hypothyroidism (AIH), this pathology rarely causes multinodular goitre; AIH might, however, accelerate the growth of an already present multinodular goitre.¹⁰ As the goitre measured about 10 cm in either lobe of the thyroid, amiodarone was not believed to be the root cause of the goitre, but might have promoted its growth.

Treatment

Total thyroidectomy was performed under ultrasound guidance with intraoperative nerve monitoring and autotransplantation of parathyroid glands (see figure 2). Postoperatively, the patient’s calcium level was slightly below normal at 8.2 mg/dL (8.4–10.6), but the parathyroid hormone was normal at 46 pg/mL (10–65). The patient was started on levothyroxine (Synthroid) 150 µg daily for iatrogenic hypothyroidism.

Outcome and follow-up

Final pathology of the thyroid showed multinodular hyperplasia and chronic lymphocytic thyroiditis in both lobes. One week following thyroidectomy, the patient’s calcium level normalised at 8.8 mg/dL and the parathyroid hormone became normal. About 1 year postoperation, the patient continued to take Synthroid 150 µg daily, and her TSH was within the reference range at 1.762 uIU/mL. At this time, she was taking amiodarone HCL 100 mg daily with a plan to continue weaning completely by cardiology. On lifting her arms, she no longer had congestion on her face and neck.

Discussion

Multiple research studies on SVC syndrome have shown that in about 75% of cases, malignancy is the aetiology.⁴ The most common malignancies to cause SVC syndrome, in the order of occurrences, are small cell carcinoma of the lung, non-small cell carcinoma of the lung, lymphoma and germ cell tumours.⁹ Of the remaining 25% of aetiologies of SVC syndrome, benign processes are the culprit. In the 1950s, there was a shift in aetiology for benign processes. Prior to 1950, the major benign processes leading to SVC syndrome were of infectious origin, such as tuberculosis mediastinitis and syphilitic aortic aneurysm.⁸ However, due to effective treatment being available for these infectious aetiologies and the advances in modern medicine, thrombosis of semipermanent intravascular catheters now accounts for most cases of benign SVC syndrome.⁹ Benign thoracic tumours account for only 1.2% cases of SVC syndrome, of which 0.4% are due to multinodular goitre.² Therefore, it is reasonable to infer that multinodular goitres are an extremely rare cause of SVC syndrome even when considering non-malignant aetiologies.

Substernal goitres are a relatively common finding with symptoms occurring once the goitre has grown. Most multinodular goitres are euthyroid and occur in women during the fifth decade of life.⁷ The most common symptoms are due to tracheal compression and include dyspnoea, coughing, stridor, wheezing and choking.^{1 10 11} Tracheal compression will occur in about 50% of symptomatic substernal goitres, while SVC syndrome only occurs 5% of the time.¹² In our literature review, there has been very few reported cases of substernal goitre resulting in both tracheal compression and SVC syndrome.

Our patient had clinically obvious SVC syndrome with mild tracheal compression noted on imaging. Considering the low likelihood of multinodular goitre causing SVC syndrome and the patient’s extensive smoking history, carcinoma of the lung was the initial suspected aetiology. Additionally, the patient did not have any palpable thyroid nodules on physical examination; however, 10–20% of patients with substernal goitre will have no cervical masses on examination.⁷ Interestingly, some studies suggest that an inability to palpate the lower poles of the thyroid may indicate substernal extension of the goitre.⁷ Our patient had been experiencing symptoms of shortness of breath and facial flushing worsening slowly over many months, likely due to the slow growth of multinodular goitres. In patients with prolonged SVC syndrome over 6 months, benign processes accounted for almost all cases.² With a benign, slow-growing process, collateral circulation consisting of the internal mammary and azygos veins is able to develop; however, over time, this too is insufficient.¹ Malignant lesions tend to be rapidly growing and present with acute-onset SVC syndrome.

Amiodarone alters thyroid hormone metabolism and is implicated in causing both hypothyroidism and hyperthyroidism. Changes in thyroid hormone levels can be seen within 3 months after initiating amiodarone therapy.¹⁰ While AIH can accelerate the growth of multinodular goitre, it is rarely implicated as the root cause of goitre. Additionally, multinodular goitres have a maximum growth potential of 20% per year.⁹ Given the massive size of this patient’s goitre and that she started amiodarone therapy just 1 year prior to symptoms, amiodarone was not believed to be the cause of her goitre. However, it is certainly possible that the drug might accelerate the growth and symptomatology of an already established multinodular goitre.

In accordance with previous research on substernal goitres, a patient presenting with gradual SVC syndrome with no evidence of palpable thyroid nodules should not be written off as having a malignancy. It is imperative to get a CT scan of the thyroid with subsequent thyroidectomy if a compressive goitre is found. Although a rare occurrence, substernal goitres extend into a tight compartment with many critical structures and should be kept on the differential when a patient presents with tracheal compression or SVC syndrome. This case highlights the importance of a thorough history taking and physical examinations along with broad differential diagnoses.

Learning points.

• This case demonstrates an unusual presentation of a large multinodular substernal goitre causing superior vena cava (SVC) syndrome and tracheal compression.

• Benign processes, let alone substernal goitres, are a rare cause of SVC syndrome.

• This patient had numerous risk factors concerning a lung malignancy as the root cause of her SVC syndrome, which would logically make sense as lung carcinoma is the most common cause of SVC syndrome.

• Additionally, this patient had a normal thyroid and thyroid-stimulating hormone levels.

• Multinodular goitre is a rare entity in iodine-rich regions of the world.

• Although amiodarone is known to cause thyroid dysfunction, including hypothyroidism, it is a very rare cause of multinodular goiter. Amiodarone has, however, been seen to accelerate the growth of an already established multinodular goitre.

• A diligent history and thorough physical examination are essential to come up with a broad differential diagnosis. This case demonstrates the importance of creating a differential diagnosis even when all symptoms and findings point to one diagnosis.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).