Substernal goitre presenting with upper and lower extremity oedema

Abstract

Substernal goitre is characterised by compressive symptoms of the airway and oesophagus. Chronic, progressive symptoms usually result in surgical removal. We report a rare presentation of substernal goitre in a male in his early 70s who suffered from severe bilateral lower extremity (LE) lymphoedema, resulting in immobility and nursing home placement, and left upper extremity lymphoedema. Our initial assessment led to a filariasis work-up, which was negative, due to the patient’s prior 2-year residence in India and service overseas. Chest CT scan revealed an incidental substernal goitre extending posterior to the left innominate vein and aortic arch to the level of the left mainstem bronchus. The patient underwent a left hemithyroidectomy via cervical excision and sternotomy and had an uneventful recovery with resolution of lymphoedema and mobility. Despite extensive literature regarding clinical presentations of substernal goitre, severe lymphoedema of the LE is not a well-established association.

Background

Discovery of unique presentations for medical conditions is essential for prompt patient diagnosis and treatment. We report a patient with none of the classical compressive symptoms of substernal goitre.¹ He suffered from progressive lymphoedema of the lower extremity (LE) for at least 5 years, resulting in immobility and nursing home placement. His clinical presentation appeared consistent with filariasis.²

Substernal goitres classically present with insidious onset of dyspnoea, choking, cough, dysphagia, uncomfortable sleep or hoarseness.^{1 3} The prevalence of substernal goitres among all cases of thyroid goitres is wide-ranging, from 2% to 19%, due to inconsistent classifications.¹ The most accepted definition of substernal goitre is an enlarged thyroid gland with greater than 50% of its volume extending beneath the thoracic inlet.⁴

The patient in this case presented with severe lymphoedema of his LEs and left upper extremity. The current literature does not demonstrate an association between substernal goitres and such extensive, debilitating lymphoedema. This case expands the current knowledge of substernal goitre clinical presentation, which may ultimately lead to quicker diagnosis and treatment for patients with rare symptoms.

Case presentation

A male in his early 70s with a 50-pack-year cigarette smoking history and prior smokeless tobacco use presented to his primary care physician for a 5-year history of worsening severe bilateral LE and left upper extremity lymphoedema. He had chronic wounds on his LEs, including a persistent ulcer on his left heel. The patient lost his ability to walk and moved into a nursing home because of disease severity. The patient’s age and smoking history increased his risk of malignancy. The primary care physician performed a CT scan of the chest due to the left upper extremity oedema, which revealed a left-sided substernal goitre.

He was referred to the otolaryngology clinic for determination of lymphoedema aetiology in relation to the incidental substernal goitre. The patient formerly lived in India for several years. His surgical history included surgical repair of a right-sided hydrocele when he was 22 years old. On physical examination, the patient had significant left-sided thyromegaly, but Pemberton’s sign was negative. We visualised lymphoedema in the LEs bilaterally and in the left upper extremity with no palpable cervical lymphadenopathy. The patient’s past international residence and prior hydrocele were concerning for filariasis.⁵

Investigations

The patient’s primary care physician performed an extensive work-up for lymphoedema prior to otolaryngology referral. Renal function studies, such as blood urea nitrogen and creatinine level, were within normal limits. The patient’s echocardiogram results showed a left ventricular ejection fraction of 65%. Doppler ultrasound of the LEs assessed vascular disease and showed normal compression flow. CT with contrast of the abdomen and pelvis was unremarkable regarding possible aetiologies of lymphoedema.

CT with and without contrast of the chest showed a substernal goitre extending posterior to the innominate vein and aortic arch with the inferior edge abutting the left mainstem bronchus and causing rightward deviation of the trachea (figure 1). The patient’s airway was patent. While discovery of the substernal goitre was serendipitous, CT is currently the gold-standard imaging modality for presurgical assessment of substernal goitres.⁶ Qureishi et al state CT as being the single most valuable tool for predicting whether a sternotomy or lateral thoracotomy will be required for thyroidectomy.⁶

Figure 1.

CT imaging of the chest shows a substernal goitre, indicated by the arrow, with extension posterior to the innominate vein and aortic arch. The inferior edge abuts the left mainstem bronchus, causing rightward deviation of the trachea.

On referral to otolaryngology with the finding of substernal goitre, the patient received a thyroid ultrasound. Imaging showed a diffusely enlarged thyroid goitre with isoechoic areas but no discrete nodules or microcalcifications. Other than the size, ultrasound findings were unimpressive and did not suggest malignancy. Fine-needle aspiration (FNA) was not performed due to the lack of discrete nodules and low risk of malignancy.⁷ Thyroid-stimulating hormone (TSH) level was decreased, but free triiodothyronine (T3) and free thyroxine (T4) were within normal ranges.

Complete blood count with differential revealed normal eosinophil counts. Filaria antibody IgG4 testing was negative. Antibody assays are sensitive for filarial infection but not specific.⁸ Specificity is limited by cross-reactivity with other helminthic diseases and the inability to differentiate current infection from past infection or prior parasite exposure.^{2 8} Lymphoscintigraphy may further evaluate lymphatic damage, and lymphatic dilation, dermal back flow or lymph flow obstruction is consistent with filarial infection.⁹ However, the patient chose not to pursue this diagnostic option.

Differential diagnosis

Differential diagnoses for chronic oedema should include evaluation of cardiac, renal and liver function, as well as chronic venous insufficiency, lymphatic aetiologies and mass effect. The patient’s primary care physician ruled out the most common aetiologies. Renal function studies were normal. Cardiac examination was unremarkable with a normal ejection fraction. The patient had no known risk factors for liver disease and reported no alcohol use. Normal compression flow on Doppler ultrasonography ruled out chronic venous stasis. CT of the chest, abdomen and pelvis showed no overt masses but revealed an incidental finding of substernal goitre that warranted referral to otolaryngology.

The two possible etiologies for the patient’s severe lymphoedema were external compression of the thoracic duct by the substernal goitre extending into the left mediastinum and chronic filariasis infection. As previously discussed, the lack of literature supporting a clinical presentation of substernal goitre causing bilateral LE and left upper extremity oedema necessitated further investigation of filarial infection causing lymphatic dysfunction. In addition, the patient had none of the usual compressive symptoms of dysphonia, dysphagia, odynophagia, dyspnoea or globus sensation. ^{1 3 10}

Developing countries of Africa and Asia are endemic to many causative species of filariasis, such as Wuchereria bancrofti, Brugia malayi and Brugia tirnori.¹¹ Specifically, 250 districts across 20 states in India are endemic to filariasis-causing organisms.¹² While multiple pathological processes may manifest as hydrocele, W. bancrofti filariasis most commonly presents as hydrocele in males.¹³ Wijaya and Pangestu reported a case of surgically repaired hydrocele with subsequent hydrocele recurrence and LE lymphoedema years later.⁵ Due to the patient’s residency history, we consulted infectious disease specialists, who suggested a filaria antibody IgG4 test that was negative.

After all other possible aetiologies were excluded, the causative reason for lymphoedema was most likely external compression of the thoracic duct by the substernal goitre. Surgical treatment options were discussed with the patient. Cardiothoracic surgery was consulted for possible need of thoracotomy.

Treatment

Prior to otolaryngology referral, the patient’s primary care physician prescribed Lasix as needed for oedema and regular wound care for the chronic LE wounds. Infectious disease specialists recommended empiric treatment with doxycycline and ivermectin. None of the medical therapies or wound care resolved the lymphoedema. The patient was referred to endocrinology prior to surgical intervention, and no medical therapy was recommended based on TSH, free T4 and free T3 studies.

Due to the degree of substernal goitre extension into the anterior mediastinum, left hemithyroidectomy via cervical incision and sternotomy performed by cardiothoracic surgery were required. The procedure went as planned without any surgical complications.

Outcome and follow-up

The patient was discharged to the nursing home on postoperative day 3 with no complications in the immediate postoperative period. The pathology result of removed thyroid tissue was nodular hyperplasia. The patient was followed for approximately 6 months after surgery. He had an uneventful recovery and was encouraged to return to the otolaryngology clinic as needed. Most importantly, the patient’s severe lymphoedema resolved. The patient was mobile after 5 years of being bed-bound and needed rehabilitation due to muscle weakness from prolonged immobilisation.

Discussion

The incidence of substernal goitre in the general population is approximately 0.02%–0.5%.¹⁴ The reported incidence of substernal goitre among all thyroid goitres varies between 2.6% and 30.4%, depending on the source due to inconsistent classifications and definitions.^{4 14–16} The most accepted definition of substernal goitre, also known as retrosternal, mediastinal or intrathoracic in the literature, is an enlarged thyroid gland with greater than 50% of its volume extending beneath the thoracic inlet.^{4 15–18}

Substernal goitres are classified into primary mediastinal goitres and secondary mediastinal goitres.^{15 19} Primary mediastinal goitres arise from an ectopic location, and secondary mediastinal goitres descend from a primary cervical location.^{15 19} Secondary mediastinal goitres represent 98% of cases.¹⁵ Substernal goitres may descend anterior to the recurrent laryngeal nerve and anterolateral to the trachea in the anterior mediastinum or posterior to the recurrent laryngeal nerve and carotid sheath in the posterior mediastinum.^{14 19} Most substernal goitres grow into the anterior mediastinum with 10%–15% located in the posterior mediastinum, and 90% of posterior mediastinal goitres propagate in the right chest due to the aortic arch, subclavian arteries and carotid arteries impeding proliferation in the left chest.^{14 19} Substernal goitres may cross the midline or extend bilaterally.^{4 14 18} Regardless of the location, secondary mediastinal goitres receive their blood supply from superior and inferior thyroid arteries^{19 20}

Substernal goitres are more predominant in women, at a 3 female:1 male ratio in the fifth and sixth decades of life, and do not increase the risk of malignancy compared with cervical goitres, as 0%–22.6% are reported to be malignant.^{14 19} Substernal goitres are asymptomatic in 15%–50% of patients, and symptomatic patients present with gradual onset of compressive symptoms, such as dyspnoea, choking, cough, hoarseness, dysphagia, uncomfortable sleep or stridor.1 3 17 21 Other reported manifestations are superior vena cava syndrome, transient ischaemic attacks, cerebral oedema, Horner’s syndrome and thyrotoxicosis.²¹ Sahsamanis et al described a unique case of substernal goitre presenting with mild left upper extremity swelling and brachiocephalic vein occlusion.³ However, to our knowledge, lymphoedema of such severity and especially of the LE as seen in our case has not been reported in the current literature.

This case has many important facets vital for expounding the current clinical picture of substernal goitre. The patient had none of the classic reported symptoms of substernal goitre, nor did he have classical physical examination findings considering the goitre’s size. Pemberton’s sign is facial congestion, cyanosis and distress due to venous compression when the patient lifts up his or her arms and can indicate increased thoracic inlet pressure.²² This sign was negative in our patient. Our hypothesis is the substernal goitre’s location was in close proximity to the thoracic duct’s drainage into the venous system at the level of the internal jugular vein’s bifurcation from the left innominate vein. This location resulted in compression of the thoracic duct, which drains the left upper extremity and both LEs, resulting in the patient’s progressive lymphoedema. Symptom severity and chronicity may be explained by compromise of the patient’s normal mediastinal anatomy. We suspect mass effect impeded development of collateral lymphatic vessels. Lymphaticovenous communications may compensate for lymphoedema.²³ However, increased venous pressure in lymph nodes prevents their canalisation.²³ Gravitational forces increase venous pressure in the LEs.²³ Impingement of the left innominate vein likely increased venous pressure in the patient’s left upper extremity. This case emphasises the myriad of symptomatic presentations possible with substernal goitre due to the vital anatomical structures located in the mediastinum.

Management of substernal goitres involves surgical excision using the cervical Kocher transverse collar incision with possible lateral thoracotomy or, in some cases, median sternotomy.^{3 24} Possible indications for a thoracic approach are excessive gland size, thoracic pain, ectopic thyroid tissue and extent of the goitre to the aortic arch or posterior mediastinum.^{1 3 25} Lin et al described CT evidence of goitre extension to the carina as the most predictive factor for thoracotomy.²⁵ The most common postsurgical complications are transient or persistent hypocalcaemia and recurrent laryngeal nerve injury.^{24 25} The risk of persistent hypocalcaemia is 0%–6%, and the risk of recurrent laryngeal nerve injury increases with total thyroidectomy versus subtotal thyroidectomy.²⁴ Our patient’s substernal goitre extended posterior to the aortic arch and abutted the left mainstem bronchus, which were indications for left hemithyroidectomy with dual cervical incision by otolaryngology and median sternotomy by cardiothoracic surgery. The patient’s lymphoedema resolved without intraoperative or postoperative complications. This case emphasises the importance of recognising rare presentations of medical conditions, as we greatly enhanced the patient’s quality of life.

Learning points.

• Discovery of rare clinical presentations for medical conditions is vital for expeditious and accurate patient care.

• Substernal goitres may be diagnosed incidentally in asymptomatic patients or in patients with atypical symptoms, as substernal goitres can manifest in a myriad of clinical presentations.

• Treatment of rare medical conditions improves quality of life for the affected patient.

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Consent obtained from next of kin.