Retro-sternal Goitre: an Overview

Abstract

Retro-sternal goitres are slow growing in nature. Dyspnoea on exertion is the most common presenting symptom due to the pressure effect of goitre on trachea. Due to the increased use of radiological investigations, retrosternal goitres are often diagnosed incidentally without any symptoms. Surgical resection is considered the gold standard management in all symptomatic patients and most of asymptomatic patients. However, “wait and watch” approach is an option, in selected asymptomatic patients, with the evolution of alternative treatment methods. So, the management of retrosternal goitre continues to be a surgical controversy. This article aims at reviewing the evidence-based practice of management of retrosternal goitres including challenges of surgery and postoperative complications.

Various Definitions and Clinical Relevance

There are more than 10 proposed definitions for retrosternal goitre in the literature. However, most definitions except 2 are not clinically relevant today [1]. The first is based on clinical criteria, i.e. “on neck examination, without being in hyperextension, thyroid gland has a portion that remains permanently retrosternal”. The other definition is also relevant to predict the need for sternotomy (Katlic`s definition), i.e. “goitre in which at least 50% is retrosternal” [2]. Goitres in the mediastinum are categorised as primary or secondary. Primary mediastinal goitres are rare and defined as those without any direct connection to the cervical part of the thyroid gland and supplied by mediastinal blood vessels. In contrast, secondary goitres are due to downward growth of the cervical gland into the mediastinum. These have continuation of blood supply from cervical branches of the thyroid arteries. Most secondary goitres grow into the anterior mediastinum, whereas 10–15% lie in the posterior mediastinum.

Symptomatology

Retro-sternal goitres can remain asymptomatic for many years, because of their slow growing nature. Majority of retrosternal goitres are diagnosed in the sixth decade of life with a male to female ratio of 1:3. Among them, 20–30% are barely palpable in the neck and about 20–40% of these lesions are diagnosed incidentally on a chest X-ray [3]. Shortness of breath on exertion, feeling of choking, orthopnoea, and dysphagia are the most common symptoms due to the pressure effect on airways and oesophagus. Presentation secondary to compression of vascular and nervous structures (i.e. superior vena cava syndrome, Horner’s syndrome, and hoarseness due to recurrent laryngeal nerve palsy) is less common.

Diagnosis

In addition to detailed history and clinical examination, computed tomography (CT) of neck and upper chest helps in the assessment of the size, extent of retro-sternal goitre, and its pressure effects on surrounding structures [4, 5]. Magnetic resonance imaging (MRI) is not routinely used as it adds little additional information to that obtained with CT [6].

Concepts of Management

The management of retrosternal goitre is decided based on whether patient is symptomatic or not, if symptomatic—their severity, the underlying cause of goitre as well as the functionality of the thyroid (i.e. hyperthyroid/hypothyroid/euthyroid). Majority of retrosternal goitres are benign. However, retrosternal goitres with suspicion of malignancy/proven malignancy (on fine needle aspiration cytology) should be surgically resected for optimal outcomes.

Symptomatic retrosternal goitre

Surgical treatment is considered the gold-standard therapeutic approach in patients with symptomatic retrosternal goitre. The goal of surgery in patients with obstructive symptoms is to resect the goitre, thereby relieving the obstructive symptoms. The risk of progression of obstruction (tracheal compression) rises further in symptomatic patients, especially in instances like internal haemorrhage or malignant transformation in the goitre.

Asymptomatic retrosternal goitre

The aim of management is to prevent further growth and subsequent development of obstructive symptoms. The treatment option in such patients is either surgical resection or “wait and watch” approach. The “wait and watch” approach has been reported in selected cases, in view of their slow growing nature [7]. Although controversial, surgery is indicated by many authors, if the retro-sternal goitres extend below the brachiocephalic vein, assuming that patients are fit for surgical intervention [8–12]. Therefore, the type of therapy is based on various factors such as the extent of retrosternal extension and also the characteristics of patient.

The arguments “in favour of surgery” in asymptomatic retrosternal goitre:

• Few goitres may go on to increase in size and become more tough for surgical resection if obstructive symptoms do develop.

• Other suppressive therapies are comparatively less effective and are associated with significant morbidity in elderly patients.

• Clinically asymptomatic may not necessarily mean no airway obstruction. Approximately 40% of asymptomatic patients showed evidence of upper airway obstruction on flow-volume loops [13].

• Elderly patients are more prone for post-surgical complications [14].

• There may be a hidden malignancy in the retrosternal component (the reported possibility of 3–22%). Sometimes, such components cannot be even biopsied due to the retrosternal location [15].

• Although small, there is a theoretical risk of sudden haemorrhage into the goitre, which can result in acute airway obstruction.

The “wait and watch” approach can be an option in asymptomatic retrosternal goitre, if:

• Patients have normal flow-volume loops with goitre at/above the level of brachiocephalic vein

• Very old and frail patients who are poor surgical candidates.

Options for Poor Surgical Candidates

If the patient is not willing for surgery/not fit for surgery, the alternative options available are radioactive ablation with/without rhTSH (recombinant human thyroid stimulating hormone) and Levothyroxine therapy.

Radioiodine therapy with/without rhTSH

This therapy is particularly useful if the retrosternal thyroid tissue is functional on thyroid radionuclide imaging. The reported size reduction with radioactive iodine is in the range of 30–60%, which is moderate and is not predictable [16, 17]. The dose of radioactive iodine used in such cases is between 100 and 400 microcurie/gm tissue [18]. In addition, pre-treatment with rhTSH prior to radioiodine has also been tried, with benefits of lower radioactive iodine doses requirement and greater reduction in thyroid gland volume. There is a theoretical possibility that radioactive iodine therapy itself may actually cause transient goitre enlargement thus worsening the obstruction.

Levothyroxine therapy

Levothyroxine therapy has been tried in sporadic, multinodular goitre with reasonable reduction in the size of goitre [19]. However, its role in large retrosternal goitre is unknown and not widely studied [20]. Other issues with this therapy include the following: (1) the size reduction is not quick, (2) Levothyroxine does not work if patient has low serum TSH levels, and (3) the goitre growth may resume as soon as this treatment is stopped.

Challenges in the Management of Retrosternal Goitre

The treatment of retrosternal goitre based on evidence-based recommendations is challenging for a variety of reasons. Majority of the available literature has low level data in the form of case series. Due to the heterogeneity of the existing data, a meta-analysis is difficult to conduct. There is a huge variation in the definition of complications like hypoparathyroidism, recurrent laryngeal nerve injury, and tracheomalacia which add to the existing confusion.

The general consensus is that medical treatment including thyroxine suppression and iodine-131 ablation are not effective in managing retrosternal goitre [21]. There is also a lack of clear indication for extra-cervical approach and the ideal extent of the initial surgery.

Query 1

Do retrosternal goitres have a higher chance of being carcinomatous as compared to cervical goitres and what are the associated risk factors in retrosternal goitres?

Literature review

Rios et al. from Spain [22] evaluated the risk factors for malignancy in multinodular goitre in 672 patients. In these, 425 patients had surgery for cervical goitre and 247 patients underwent surgery for a retro-sternal goitre. Histopathology revealed 10.7% had carcinoma in a cervical goitre; however, only 5.7% had cancer in a retrosternal goitre. On bivariate analysis, presence of a retrosternal component appears to have a protective effect for carcinoma (p = 0.029); however, this was not confirmed by multivariate analysis.

Another retrospective analysis was done on a prospectively maintained data of 10,164 patients [23] who underwent thyroidectomy. Sub-analysis of 234 patients who underwent surgical resection for retrosternal goitre revealed that 7.7% were diagnosed with malignancy on histopathology.

Conclusion

The available data suggests that the incidence of cancer in retrosternal goitres is no higher than the incidence of cancer in cervical goitres.

Query 2

How often is an extra-cervical approach needed and what are the predictive factors for the same?

Literature review

A retrospective analysis from Australia [24] reviewed 1106 patients with thyroid disease. A subgroup analysis on 199 patients of retrosternal goitre was done. All such cases were completed by cervical approach and no extra-cervical procedures were required.

Other retrospective review from Cleveland clinic [10] on 381 patients revealed that out of 116 patients who had undergone surgery for retrosternal goitre, the extra-cervical approach was used in only 1.7% of cases.

Conclusion

Therefore, the data suggest that, for most patients, expert endocrine surgeons utilise an extra-cervical approach approximately 2% of the time to remove a retrosternal goitre safely. A sternotomy or thoracotomy appears more likely in cases of a primary retrosternal goitre or a mass larger than the thoracic inlet.

Query 3

How often do you encounter permanent hypoparathyroidism and permanent nerve injury while removing retrosternal goitre as compared to cervical goitre?

Literature review

Total thyroidectomy for a cervical goitre, performed by surgeons experienced with the procedure, results in permanent hypoparathyroidism in 1–2% of patients and permanent nerve injury (RLN, external branch of the superior laryngeal) in 1–2% of patients [25–27]. The Murcia study enrolled a total of 301 patients—239 cervical goitre and 62 retrosternal goitre. Postoperatively, 0.4% in the cervical goitre group, and 1.6% in the retrosternal group suffered permanent hypoparathyroidism. No patients had permanent RLN injury in cervical group, whereas 1.6% had in retrosternal group. Multivariate analysis revealed presence of hyperthyroidism and an intrathoracic component was found as independent risk factors for postoperative complications.

Conclusion

Considering this data, there may be a higher rate of permanent hypoparathyroidism and unintentional permanent RLN injury when total thyroidectomy is performed to remove a retrosternal goitre than to remove a cervical goitre alone.

Query 4

What is the incidence of tracheomalacia and tracheostomy after thyroidectomy for substernal goitres, and what are the associated factors predicting these complications?

Literature review

A study from Sudan [28] enrolled 103 patients with large goitres who underwent thyroidectomy. In 5.8% of patients, tracheomalacia was found. On detailed analysis, factors that can predict the need for tracheostomy were 1. Duration of goitre > 5 years with progressive stridor, presence of a retrosternal goitre, significant deviation, and/or compression of the trachea in preoperative radiological imaging.

Conclusion

The presence of a retrosternal goitre, especially being present more than 5 years and causing significant tracheal compression, is likely a risk factor for tracheomalacia and tracheostomy.

How to Decide Surgical Approach?

Performing surgery in retrosternal goitre is a demanding task for the surgeon, and the outcome depends on the surgeons’ experience. The size of the retrosternal extension will determine the approach which can be a cervical incision, a partial or total sternotomy and even thoracotomy.

Fibre-optic bronchoscopy-guided tracheal intubation is recommended in all cases of large goitres with retro-sternal extensions causing significant tracheal compression. In addition, the routine use of fibre-optic bronchoscopy during extubation should be encouraged to assess tracheomalacia component as post-procedure; the tracheal wall loses the surrounding support and can collapse in antero-posterior direction leading to respiratory obstruction.

Huins et al. [29] recommended performing a cervical approach when the substernal goitre is above the aortic arch, a partial sternotomy when the inferior limit of the goitre is between the aortic arc and the pericardium, and a full sternotomy when the thyroid extension goes beyond the right auricle.

Mercante et al. [30] classified the retrosternal goitre into 3 grades based on the lower limit of extension. Grade I goitre is when the inferior limit of the thyroid gland is between the thoracic outlet and the aortic arch. In grade II, the inferior border of goitre lies in between the concavity and convexity of the aortic arch and grade III is when the inferior margin of retrosternal component extends further down the aortic arch. On correlation of the grade of extension and the surgical approach, he found an odds ratio 24-fold higher for an extra-cervical approach in grade II goitres and sevenfold higher in grade III goitres as compared with grade I.

Cichon et al. [31] mentioned that re-surgery increased the chances that a thoracic approach would be required because of the presence of adhesions to surrounding tissues. Other authors also reported that goitres that extended beyond the carina or into the posterior mediastinum and invasive carcinoma have been proposed as indicators of the need to use a thoracic approach [32–35]. A study conducted by Nankee et al. [36] found a few absolute indicators for thoracic approach being required. This included patients who had a higher incidence of preoperative symptoms of chest pressure and voice complaints. Another similar study by Cohen et al. [37] reported that the paramount predictive factor as to whether a goitre can safely be removed through a cervical approach is the presence of a clear tissue plane around the nodule in the mediastinum which can be obtained through a pre-operative CT scan. If such a clear plane is not present, preparations should be made for sternotomy.

Therefore, taking all factors into consideration, the likelihood of using an extra-cervical approach increases by presence of a huge mass whose size is greater than the thoracic inlet, involvement of the posterior mediastinum, extension of the goitre beyond the aortic arch, extension of the thyroid tissue towards the tracheal bifurcation, a recurrent retrosternal goitre, primary mediastinal goitre, a malignant thyroid goitre with suspicion of surrounding structures, and a huge goitre whose lower border is inaccessible from neck. Although the abovementioned factors provide an idea about the surgical approach, the final decision of extra-cervical approach should be made on table.

The definitive diagnosis of tracheomalacia is done with observation of tracheal membranous part collapse into lumen despite the normal motion of vocal cord [11, 12]. It seems that the causes of contradiction results are the absence of accepted definitions about tracheomalacia; besides, in some studies, the diagnosis was based on clinical diagnosis. If the diagnosis is done only clinically, so most of the post-thyroidectomy respiratory problems will be reported as tracheomalacia, as in our patient that we thought that causes are tracheomalacia until bronchoscopy showed bilateral recurrent laryngeal nerve palsy.

Feasibility of Minimally Invasive Approaches

In retrosternal goitre where cervical approach alone is not feasible, the use of video-assisted thoracoscopic surgery (VATS) instead of sternotomy/thoracotomy has been attempted by several researchers with promising results. This method can provide the advantages of minimally invasive approach such as less pain, early recovery, and less hospital stay. However, the evidence supporting this is of low quality which is based on few small case series [38, 39]. The limitations of VATS such as 2D visualisation and difficult access often discourage surgeons to follow this approach.

To overcome the disadvantages of the VATS approach, few surgeons started using robotic access for better results. Robotic surgery offers 3D visualisation, depth perception, and superior manoeuvrability of the instruments due to endowrist technology. These technical advancements offer precise dissection of thyroid gland and its mediastinal extension [40]. Robot also has the advantage of accessing the remote areas such as mediastinum [41]. Wang et al. reported the role of robotic approach for dissection of retrosternal component of goitre [42]. The major drawbacks of this method are higher cost and long learning curve apart from very limited reported experience.

Although this combined cervico-mediastinal approach, i.e. minimal access dissection and mobilisation of retrosternal component along with cervical incision for dissection and removal of cervical component, is a rising trend to deal with huge retrosternal goitres, the exact role of minimal access methods in dealing this complex clinical entity remains to be elucidated.

Postoperative Complications

Permanent hypoparathyroidism, recurrent laryngeal nerve injury, and tracheomalacia are the most often encountered complications after surgical resection of retrosternal goitre. The incidence of hypoparathyroidism and recurrent laryngeal nerve palsy were reported as high as 5% and 13%, respectively, after surgery for retrosternal goitre [6, 43]. Such complications are significantly higher if compared with thyroidectomy for cervical goitre (1–2%) [15]. In addition, tracheomalacia is also a known complication (1–2%), for which the risk factors being long standing goitres (> 5 years) and significant compression of trachea in pre-operative imaging. In a study specifically looking at postoperative tracheomalacia, majority of the patients could be immediately extubated, and all were successfully extubated by 10 days [44]. Due to the rarity of this complication, there are no standard guidelines for the optimal management. However, intubation for few days with/without tracheostomy is associated with a favourable outcome [45].

Conclusion

Exertional dyspnoea is the most common presenting symptom in retrosternal goitre due to the compression of trachea. Surgical resection is the gold standard management in all symptomatic patients and most of asymptomatic patients. However, “wait and watch” approach can be tried in asymptomatic patients with normal flow-volume loops whose goitres end at the level of the brachiocephalic vein or higher. If the patient is not willing/not fit for surgery, radioactive iodine ablation is an alternative option. However, the reduction in thyroid volume with radioiodine is only moderate and is unpredictable. The size of the retrosternal extension will determine the approach which can be a cervical incision alone or with addition of partial or total sternotomy and even thoracotomy. Recently, minimally invasive techniques such as VATS and robotic methods have also been tried for mediastinal mobilisation with encouraging early results. Postoperative complications such as permanent hypoparathyroidism, recurrent laryngeal nerve palsy, and tracheomalacia are observed more often after retrosternal goitre surgery compared to cervical goitre. Therefore, surgical intervention for retrosternal goitre should be attempted only by experienced surgeons in high-volume centres to minimise complication rates.

Declarations

Conflict of Interest

The authors declare no competing interests.