Introduction
An enlarged thyroid gland is referred to as a goiter. The thyroid gland is surrounded by thin muscles, subcutaneous fat, and skin and experiences minimal resistance as it grows, typically expanding anteriorly or laterally. When enlarged, the thyroid gland is usually visible and easily palpable; however, detection may be complicated by body habitus. If the thyroid gland grows inferiorly, passing through the thoracic inlet into the thoracic cavity, or if ectopic thyroid tissue is present in the mediastinum, it is referred to as a "substernal goiter."[1]
According to the American Thyroid Association, clinical criteria define a substernal goiter as the presence of a retrosternal portion of the thyroid gland observed during a cervical examination without hyperextension. Substernal goiter is also known by various names, including retrosternal goiter, cervicomediastinal goiter, mediastinal goiter, aberrant goiter, mediastinal aberrant goiter, mobile goiter, plunging goiter, wandering goiter, spring goiter, retroclavicular goiter, and intrathoracic goiter.[1] In addition, while various definitions of "substernal goiter" exist, this activity will adhere to the definition provided above.
Substernal goiters are classified into primary and secondary mediastinal goiters. Primary mediastinal goiters originate from an ectopic location unrelated to the normal thyroid gland, while secondary mediastinal goiters descend from a primary cervical location. Secondary mediastinal goiters account for 98% of cases, with ectopic thyroid tissue in the chest causing de novo substernal goiter being rare, representing only 2% of all substernal goiters.[2][3]
Substernal goiter may involve one or both thyroid lobes and can cause tracheal deviation or compression and, less commonly, compression of the esophagus or venous structures. Tracheal compression has been reported in 35% to 73% of substernal goiters.[3] Approximately 10% of substernal goiters are located in the posterior mediastinum, with 90% of these being right-sided due to anatomical constraints from the left-sided subclavian arteries and the aortic arch, which limit left-sided expansion.[4]
Some studies define substernal goiter as any portion of the thyroid gland that extends through the thoracic inlet, whereas others require that 50% or more of the thyroid be located below the thoracic inlet. This difference in definition contributes to the variability in results among studies. If the lower tip of the thyroid moves above the thoracic inlet when the patient extends their neck, the abnormality is considered positional and does not qualify as a substernal goiter.
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles
10 free questions in your specialty
Free CME/CE Activities
Free daily question in your email
Save favorite articles to your dashboard
Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The etiology of substernal goiter is similar to that of cervical goiter, and up to 16% of the global population is affected by goiter.[5] The most common cause worldwide is iodine deficiency. Additionally, chemicals that interfere with iodine uptake, block thyroid receptors, or disrupt thyroid metabolism can contribute to goiter formation. These include perchlorate, thiocyanate, nitrate, bisphenol-A, triclosan, isoflavones, and various pesticides.
In addition, genetic factors may also contribute to goiter formation, although no single gene has been identified. Environmental factors, such as cigarette smoke, iodine-deficient soil, and selenium deficiency, can also influence goiter development.[6] Goiters usually begin as diffuse enlargement and may progress to a nodular form. Nodular goiters can be classified as toxic (producing thyroid hormone) or nontoxic.[6] Please see StatPearls' companion reference, "Goiter," for further information.
The growth of the thyroid from the cervical region through the fascial planes into the inferior mediastinum, resulting in substernal goiter, may be facilitated by gravity, traction forces during swallowing, and negative mediastinal pressure during inspiration. Other anatomical factors that may contribute to faster goiter growth in patients include a short cervical trachea, strong neck muscles, and a short neck.[1]
Epidemiology
The prevalence of substernal goiter in the general population is unknown due to the lack of epidemiological studies. However, with 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 and occurs four times more frequently in females.[4][7] A recent surgical series reported a substernal goiter rate of 7% among patients who underwent thyroid surgery.[8]
Pathophysiology
The thyroid grows in the direction of the area with the least resistance. The trachea and vertebrae restrict posterior growth, while the resistance of the strap muscles limits anterior growth. As the thyroid grows anteriorly, it stretches the strap muscles, leading to the development of cervical goiter.
The thyroid then grows inferiorly through the thoracic inlet and into the mediastinum until the strap muscles can no longer stretch. Due to the absence of anatomical structures, there is only thin areolar tissue between the thoracic inlet and the inferior portion of the thyroid. The blood supply for most substernal goiters primarily comes from the inferior thyroid artery.[1][9] Occasionally, cervical goiters that descend into the thoracic cavity lose continuity with thyroid tissue in the neck and appear as isolated occurrences in the chest. In some cases, a substernal goiter may be connected to a cervical goiter by a fascial extension.[1]
Approximately 80% to 90% of substernal goiters are located in the anterior mediastinum, while 10% to 20% are found in the posterior mediastinum.[9] Based on the anatomical extension of the goiter, it can be classified into 3 types, as mentioned below.
- Type I: The lower pole of the goiter reaches the superior margin of the aortic arch.
- Type II: The goiter is predominantly located posterior to the sternum, with the lower pole positioned behind the aortic arch or extending into the posterior mediastinum.
- Type III: A significant intrathoracic goiter protrudes into the thorax.[10]
History and Physical
Patients with substernal goiter are often asymptomatic, with incidental detection occurring through chest x-rays, computed tomography (CT), or magnetic resonance imaging (MRI). When present, symptoms are typically mechanical or compressive in nature, although clinical manifestations of hypothyroidism or hyperthyroidism may also occur. Displacement of the aerodigestive structures can lead to localized compressive or obstructive symptoms affecting the esophagus or airway.[11][12] Acute airway obstruction may occur due to spontaneous nodule rupture or trauma. Another potential emergency is right heart failure resulting from compression of the pulmonary artery.[1]
The most common obstructive symptom of substernal goiter is exertional dyspnea, followed by a choking sensation, cough, and stridor. As patients with substernal goiter are often in their sixth decade or later, accurately determining the etiology of dyspnea is essential, as comorbidities such as chronic obstructive pulmonary disease (COPD), asthma, or congestive heart failure are common contributors.[13] Other symptoms may include insomnia, wheezing, difficulty swallowing due to esophageal compression, hoarseness from recurrent laryngeal nerve compression, prominent jugular veins, superior vena cava syndrome caused by venous compression, and orthopnea.[1][12] Phrenic nerve palsy and subsequent hypoventilation represent an unusual presentation of intrathoracic enlargement of the goiter.[14][15] Due to the typically slow growth of goiters, the condition may remain asymptomatic or present with insidious symptoms. Obstructive symptoms result from the enlargement of thyroid tissue at the thoracic inlet or within the chest cavity, as these confined anatomical spaces lack the capacity to accommodate the enlarging goiter.
Hyperthyroidism and hypothyroidism may coexist with substernal goiter, each presenting with its characteristic signs. The enlarged cervical component of the substernal goiter may be visible or palpable during a physical examination. Tracheal compression may result in audible stridor, a high-pitched sound primarily heard during inspiration, caused by airway obstruction outside the chest cavity. This contrasts with wheezing, which arises from lower respiratory tract obstruction and produces a continuous whistling sound heard more prominently during expiration. Despite these differences, wheezing can also present as a symptom of substernal goiter.[1]
The Pemberton sign may be evaluated during a physical examination by instructing the patient to raise both arms until the medial sides touch the lateral aspects of the head for at least 1 minute. Facial congestion, neck vein distension, hoarseness, or dyspnea during the maneuver indicate a positive Pemberton sign, suggesting compression at the thoracic inlet. Arm elevation spirometry with flow-volume loops has been proposed to enhance sensitivity in detecting upper airway obstruction and to provide an objective assessment of the Pemberton sign.[16]
The "cork effect" of the thyroid at the thoracic inlet is believed to cause compression of the surrounding anatomical structures, contributing to a positive Pemberton sign. This effect can result from a goiter descending into the thoracic cavity or from elevation of the thoracic inlet toward the neck. A cork effect may cause symptoms when a patient with substernal goiter flexes or hyperflexes their head. In a study, magnetic resonance angiography of a patient with a positive Pemberton sign revealed that the clavicles moved and compressed the external and internal jugular veins at their confluence with the subclavian vein, pressing against the enlarged thyroid. This was not due to a true "cork effect" but resembled a nutcracker mechanism, where the medial heads of the clavicles compress venous structures against the enlarged thyroid within the narrowed thoracic inlet.[17]
Evaluation
Initially, thyroid-stimulating hormone (TSH) levels should be measured. If TSH is abnormal, total or free T4 and total or free T3 can be obtained. Alternatively, free T4, free T3, and TSH can be measured simultaneously to assess thyroid hormone status. During the initial evaluation, some healthcare professionals may also measure anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies to assess for Hashimoto thyroiditis, which can coexist with substernal goiter.
A thyroid ultrasound is recommended to assess the cervical component of the goiter. However, it cannot evaluate the extent or characteristics of the intrathoracic portion of the substernal goiter, as ultrasound waves cannot penetrate bone and do not propagate well through the air in the lungs.
A chest x-ray may reveal an upper mediastinal mass with tracheal deviation or compression. This imaging technique can also show hemi-diaphragmatic elevation, which indicates phrenic nerve palsy.[14]
The preferred imaging modalities are CT or MRI of the chest, as they accurately assess the size, extent, and anatomical relationships of the substernal goiter. Iodinated contrast used in CT scanning can induce hyperthyroidism and prevents the use of nuclear medicine thyroid scans until the iodine is cleared from the body. A nuclear medicine thyroid scan (using iodine or technetium) may reveal thyroid tissue in the thoracic cavity. The absence of uptake could suggest a cold nodule in the mediastinum but does not rule out a substernal goiter.
The most important and recommended imaging modality is chest CT, which allows for detailed characterization of the thyroid mass, including its size, morphology, and anatomical relationship with surrounding structures. CT also enables the detection of tracheal deviation and quantification of tracheal compression. Surgical intervention is required if the tracheal dimension measures 10 mm or less.
Barium esophagography or upper endoscopy may be considered if dysphagia is the predominant symptom, although these are less commonly used.
A pulmonary function test with a flow-volume loop study is essential. Even in asymptomatic patients, pulmonary function tests may reveal abnormalities. Substernal goiter can result in a blunted flow-volume loop, with similar flow limitation during both inspiration and expiration, along with flattening of both limbs. This pattern indicates mechanical fixed upper airway obstruction. Pulmonary function tests help differentiate substernal goiter from other causes of dyspnea, such as COPD.
hyroid cancer has been reported in up to 21% of cases involving substernal goiters.[9][13][18] A recent guideline on the surgical management of adult thyroid disease estimates the risk of malignancy in substernal goiter at 9% to 13%.[3] Although thyroid fine-needle aspiration is the gold standard for evaluating cervical thyroid nodules, it is not recommended for substernal goiters. One potential complication of thyroid fine-needle aspiration is hemorrhage. Bleeding within a substernal goiter or thyroid nodule may lead to sudden enlargement and respiratory compromise. Insertion of the needle into the thoracic cavity also carries the risk of causing pneumothorax. As most substernal goiters are multinodular, some nodules may be suitable for biopsy. Molecular testing can be performed on nodules with indeterminate pathological findings, potentially providing additional diagnostic information.[19]
Treatment / Management
If the patient presents with hypo- or hyperthyroidism, this should be appropriately addressed. Surgery is the treatment of choice for symptomatic substernal goiter. The management of asymptomatic substernal goiter remains controversial, as there is no universally agreed-upon approach. For asymptomatic patients without fixed upper airway obstruction or significant tracheal compression, expectant observation may be considered, with regular monitoring for symptoms or changes in the goiter's size, tracheal diameter, or thyroid function. In such cases, the patient should avoid iodine-containing supplements, multivitamins, medications, and iodinated contrast agents to prevent iodine-induced hyperthyroidism.
Expectant monitoring involves periodic thyroid function tests and chest CT scans, typically 1 year after the initial assessment, with less frequent follow-up if stable. If no abnormalities develop in the observed parameters, periodic monitoring continues. If there is growth of the substernal goiter, evolving tracheal compression with a decrease in tracheal size, or the development of thyroid autonomy with hyperthyroidism, surgery becomes necessary. In patients with hyperthyroidism, antithyroid drugs and a beta-blocker should be administered 2 weeks before surgery, provided there are no contraindications to beta-blockers. Additionally, an inorganic iodine solution should be given 7 to 10 days before surgery to prevent a thyroid storm. If the patient has only subclinical hyperthyroidism, no specific preparation for surgery is required.
Proponents of surgery for asymptomatic patients express concern that a substernal goiter may eventually grow and compress intrathoracic structures if left untreated, although no studies have documented this process. This would require a longitudinal study, which has not yet been conducted for substernal goiter. Another concern is the potential presence of undiagnosed thyroid cancer within the substernal goiter. Additionally, as patients age, delayed surgery may make the procedure more challenging, with a higher complication rate. Over time, patients may transition from a lower surgical risk category to a higher one.
Surgical intervention has been associated with a 95% to 98% resolution of compressive symptoms when tracheal narrowing progresses to 35% or more. Tracheal compression of 35% or greater is often cited as an indication of surgical intervention.[20] The limit of 35% was not determined prospectively but by comparing the narrowest tracheal size with the widest tracheal size on cross-sectional CT imaging.(B2)
Suppressive therapy with levothyroxine to lower TSH levels is ineffective for treating substernal goiter. Radioactive iodine therapy is also not effective and is reserved for patients who are not surgical candidates. However, radioactive iodine treatment can obscure or miss underlying malignancy. Additionally, radiation-induced thyroiditis in the closed chest cavity may theoretically cause respiratory compromise.[1]
The definitive treatment for substernal goiter is surgery, with total thyroidectomy being the preferred approach. Please see StatPearls' companion resource, "Substernal Thyroidectomy," for more information. The cervical approach is utilized in most cases. A recent study found that 78.3% of patients underwent total thyroidectomy, 18.3% had a subtotal thyroidectomy, and 3.3% had a lobectomy.[4] The Definitive Surgical Management of Thyroid Disease in Adults Guidelines recommend total thyroidectomy for bilateral goiter as the standard, although there are clinical scenarios where total thyroidectomy may not be feasible or possible.[3] An extra-cervical approach is required for patients in 1% to 8% of substernal goiter surgeries.[8][13][21] This approach may range from partial sternotomy to thoracotomy. Due to the complexity of substernal goiter surgery, it should be performed at a referral center.[8] A recent study found that 17% of patients undergoing substernal goiter surgery required an extra-cervical approach, highlighting the variability of this rate across different institutions.[7](B2)
Mercante et al proposed a classification system for substernal goiter based on the position of the thyroid in relation to the aortic arch, as mentioned below.[22] (B2)
- Grade I is when the lower border of the thyroid is above the aortic arch.
- Grade II is when the lower border is between the convex and concave parts of the aortic arch.
- Grade III when the lower border is below the concave part of the aortic arch.
The need for an extra-cervical approach is significantly higher for grade II and III goiters. Indications for sternotomy include goiter extension to or below the aortic arch, a dumbbell-shaped goiter, an iceberg-shaped goiter with more than 70% of thyroid volume in the mediastinum, posterior mediastinal location, recurrent goiter, ectopic substernal goiter with blood supply from mediastinal vessels rather than the inferior thyroid artery, or thyroid cancer with potential invasion of mediastinal structures.[7][23](B2)
Surgery for substernal goiter is associated with a higher complication rate than surgery for cervical goiter.[18] A recent study reported the 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%).[21] The mortality rate for substernal goiter surgery has been reported as high as 2.3%.[18](B2)
A clinical decision should be made for expectant observation versus surgical intervention in asymptomatic patients based on their symptoms, signs, clinical, laboratory, and radiological features, as well as surgical risk. Surgery is required for symptomatic patients with compression of intrathoracic vital structures. Patients with a positive Pemberton sign should also undergo surgery.[3] After thyroidectomy, levothyroxine replacement should begin at a dose of 1.6 mcg/kg of body weight, with lower and gradually increasing doses for older or cardiac patients.
Differential Diagnosis
The differential diagnosis for mediastinal masses includes a variety of tumors and cysts, each with distinct characteristics and clinical implications. These include:
- Thymoma and thymic carcinoma
- Bronchogenic cyst
- Lymphoma
- Teratoma and germ cell tumors
- Pericardial cyst
- Ganglioneuromas and other neurogenic tumors of the posterior mediastinum
Prognosis
No specific study exists on the natural history of substernal goiter, and no prospective studies compare expectant monitoring with surgery. The concept that substernal goiters enlarge and eventually cause symptoms or severe respiratory distress if left untreated has not been definitively proven.[18]
A retrospective study measured thyroid volume using CT and found that an intrathoracic thyroid volume of 162 cm or more below the thoracic inlet was a key factor in determining the need for thoracotomy.[7] In the future, intrathoracic thyroid volume may be used to decide between cervical and extra-cervical approaches.
Complications
Substernal goiter can lead to various complications due to its impact on surrounding anatomical structures, which are listed below.
- Tracheal and venous compromise: Substernal goiter can compromise the trachea, venous vasculature, and other surrounding intrathoracic anatomical structures.
- Life-threatening respiratory compromise: Substernal goiter can lead to life-threatening respiratory compromise if sudden enlargement or bleeding occurs within the goiter.
- Thyroid cancer: A study reported that 72% of papillary thyroid cancer foci were intrathoracic, while 28% were cervical, in patients who underwent surgery for substernal goiter. When analyzed per nodule, rather than per subject in statistical analysis, incidental foci of papillary carcinoma were significantly more common in substernal goiter than cervical goiter (31% versus 19%).[13]
- Phrenic nerve paralysis.
- Horner syndrome: This is caused due to compression of the cervical sympathetic chain.
- Jugular vein thrombosis.
- Cerebrovascular steal syndrome.
- Superior vena cava syndrome.
- Tracheomalacia: Long-term pressure on the trachea can cause tracheomalacia (weakening of tracheal cartilage), leading to airway collapse.[24]
Deterrence and Patient Education
Preventing goiter will also reduce the risk of developing a substernal goiter. The natural progression of goiter involves continued growth, the formation of nodules, and the development of functional autonomy, transitioning from a nontoxic to a toxic multinodular goiter. The longer a goiter is present, the larger it will become, and as the goiter grows, TSH levels tend to decrease.
The most effective approach to effectively prevent goiter on an individual level is to ensure adequate iodine intake, which can help prevent goiter and support overall health. The recommended daily iodine intake is as follows:
- Adults and adolescents: 150 mcg/d
- Pregnant women: 220 mcg/d
- Lactating women: 290 mcg/d
- Children (aged 1-11): 90 to 120 mcg/d
- Infants: 110 to 130 mcg/d
Additionally, dietary or iatrogenic goitrogens should be avoided. Goiter caused by autoimmune thyroid disease or inborn errors of metabolism requires medical intervention and cannot be prevented. Patients should be educated on the importance of adequate dietary iodine, avoiding goitrogens, and adhering to annual health examinations.
Pearls and Other Issues
Surgical intervention is widely agreed upon for symptomatic patients, although there is no consensus regarding the management of asymptomatic cases. Future studies should compare the outcomes of expectant observation versus surgery in asymptomatic patients with substernal goiter.
Enhancing Healthcare Team Outcomes
Due to the widespread use of chest imaging and cancer screening, substernal goiter is expected to be diagnosed more frequently and earlier. Patients with substernal goiter should be referred to an endocrinologist for evaluation and management. If surgery is indicated, a consultation with a surgeon experienced in thyroid procedures is recommended. For cases requiring an extra-cervical approach, a thoracic surgery consultation is necessary. Surgery for substernal goiter should be performed at tertiary institutions with expertise in thyroid surgery and its associated complications.
Ethical considerations are crucial when determining treatment options and respecting patient autonomy in decision-making. Responsibilities within the interprofessional healthcare team should be clearly defined, with each member contributing their specialized knowledge and skills to optimize patient care. Effective communication among interprofessional healthcare providers promotes a collaborative environment where information is shared, questions are encouraged, and concerns are addressed promptly.
Lastly, care coordination is essential for ensuring seamless and efficient patient care. Physicians, advanced practitioners, nurses, pharmacists, and other healthcare professionals must collaborate to streamline the patient's journey, from diagnosis through treatment and follow-up. This coordination minimizes errors, reduces delays, and enhances patient safety, ultimately improving outcomes and delivering patient-centered care that prioritizes the well-being and satisfaction of individuals affected by substernal goiter.
References
Unlu MT, Aygun N, Kostek M, Isgor A, Uludag M. Substernal Goiter: From Definitions to Treatment. Sisli Etfal Hastanesi tip bulteni. 2022:56(2):167-176. doi: 10.14744/SEMB.2022.30806. Epub 2022 Jun 28 [PubMed PMID: 35990303]
Daggett RLB, Farishta D, Cuellar H, Nathan CO. Substernal goitre presenting with upper and lower extremity oedema. BMJ case reports. 2021 Nov 1:14(11):. doi: 10.1136/bcr-2021-245036. Epub 2021 Nov 1 [PubMed PMID: 34725062]
Level 3 (low-level) evidencePatel KN, Yip L, Lubitz CC, Grubbs EG, Miller BS, Shen W, Angelos P, Chen H, Doherty GM, Fahey TJ 3rd, Kebebew E, Livolsi VA, Perrier ND, Sipos JA, Sosa JA, Steward D, Tufano RP, McHenry CR, Carty SE. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Annals of surgery. 2020 Mar:271(3):e21-e93. doi: 10.1097/SLA.0000000000003580. Epub [PubMed PMID: 32079830]
Chávez Tostado KV, Velázquez-Fernandez D, Chapa M, Pantoja Millán JP, Salazar MS, Herrera MF. Substernal Goiter: Correlation between Grade and Surgical Approach. The American surgeon. 2018 Feb 1:84(2):262-266 [PubMed PMID: 29580356]
Dauksiene D, Petkeviciene J, Klumbiene J, Verkauskiene R, Vainikonyte-Kristapone J, Seibokaite A, Ceponis J, Sidlauskas V, Daugintyte-Petrusiene L, Norkus A, Zilaitiene B. Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects. International journal of endocrinology. 2017:2017():8401518. doi: 10.1155/2017/8401518. Epub 2017 Mar 5 [PubMed PMID: 28356911]
Unlu MT, Kostek M, Aygun N, Isgor A, Uludag M. Non-Toxic Multinodular Goiter: From Etiopathogenesis to Treatment. Sisli Etfal Hastanesi tip bulteni. 2022:56(1):21-40. doi: 10.14744/SEMB.2022.56514. Epub 2022 Mar 28 [PubMed PMID: 35515961]
Sormaz İC, Uymaz DS, İşcan AY, Özgür İ, Salmaslıoğlu A, Tunca F, Şenyürek YG, Terzioğlu T. The Value of Preoperative Volumetric Analysis by Computerised Tomography of Retrosternal Goiter to Predict the Need for an Extra-Cervical Approach. Balkan medical journal. 2018 Jan 20:35(1):36-42. doi: 10.4274/balkanmedj.2017.0161. Epub 2017 Aug 25 [PubMed PMID: 28840845]
Doulaptsi M, Karatzanis A, Prokopakis E, Velegrakis S, Loutsidi A, Trachalaki A, Velegrakis G. Substernal goiter: Treatment and challenges. Twenty-two years of experience in diagnosis and management of substernal goiters. Auris, nasus, larynx. 2019 Apr:46(2):246-251. doi: 10.1016/j.anl.2018.07.006. Epub 2018 Jul 25 [PubMed PMID: 30055961]
Sandasecra S, Yahya MM, Zuhdi Mamat A, Soh JY, Ramely R, Aziz ME. A Monster in the Chest: A Tale of a Goiter. Cureus. 2022 Jun:14(6):e25827. doi: 10.7759/cureus.25827. Epub 2022 Jun 10 [PubMed PMID: 35822139]
Zuo T, Gao Z, Chen Z, Wen B, Chen B, Zhang Z. Surgical Management of 48 Patients with Retrosternal Goiter and Tracheal Stenosis: A Retrospective Clinical Study from a Single Surgical Center. Medical science monitor : international medical journal of experimental and clinical research. 2022 Aug 11:28():e936637. doi: 10.12659/MSM.936637. Epub 2022 Aug 11 [PubMed PMID: 35949114]
Level 2 (mid-level) evidenceKnobel M. An overview of retrosternal goiter. Journal of endocrinological investigation. 2021 Apr:44(4):679-691. doi: 10.1007/s40618-020-01391-6. Epub 2020 Aug 11 [PubMed PMID: 32780357]
Level 3 (low-level) evidenceWang YH, Chiang PL, Lin AN, Wang CK, Lee CY, Chou CK, Chang YH, Chi SY, Luo SD, Lin WC. Long-term outcomes of radiofrequency ablation for intrathoracic goiter up to 5 years: evaluated by computed tomography/magnetic resonance imaging and ultrasound. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2024:41(1):2378865. doi: 10.1080/02656736.2024.2378865. Epub 2024 Jul 14 [PubMed PMID: 39004424]
Sahbaz NA, Tutal F, Aksakal N, Acar S, Aksu KI, Barbaros U, Erbil Y. Cancer Frequency in Retrosternal Goiter. The American surgeon. 2017 Dec 1:83(12):1390-1393 [PubMed PMID: 29336760]
Shioya N, Inoue N, Kawashima N, Tsukamoto Y, Nakayama M, Hazama K, Shichinohe Y, Suzuki F, Honma N. Enlargement of Intrathoracic Goiter with Unilateral Phrenic Nerve Paralysis Leading to Cardiopulmonary Arrest. Internal medicine (Tokyo, Japan). 2021 Jan 1:60(1):91-97. doi: 10.2169/internalmedicine.5075-20. Epub 2020 Sep 5 [PubMed PMID: 32893229]
Cabrero-Rodríguez C, Mendoza-Barrios A, Redondo Torres E. Unilateral Phrenic Nerve Palsy in a Patient With a Giant Intrathoracic Goiter. Archivos de bronconeumologia. 2024 Mar:60(3):175-176. doi: 10.1016/j.arbres.2023.12.010. Epub 2023 Dec 20 [PubMed PMID: 38160167]
Resende PN, de Menezes MB, Silva GA, Vianna EO. Pemberton Sign: A Recommendation to Perform Arm Elevation Spirometry With Flow-Volume Loops. Chest. 2015 Dec:148(6):e168-e170. doi: 10.1378/chest.15-0700. Epub [PubMed PMID: 26621294]
De Filippis EA, Sabet A, Sun MR, Garber JR. Pemberton's sign: explained nearly 70 years later. The Journal of clinical endocrinology and metabolism. 2014 Jun:99(6):1949-54. doi: 10.1210/jc.2013-4240. Epub 2014 Mar 19 [PubMed PMID: 24646105]
Level 3 (low-level) evidenceLanderholm K, Järhult J. Should asymptomatic retrosternal goitre be left untreated? A prospective single-centre study. Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2015 Jun:104(2):92-5. doi: 10.1177/1457496914523411. Epub 2014 Apr 23 [PubMed PMID: 24759378]
Muzza M, Colombo C, Pogliaghi G, Karapanou O, Fugazzola L. Molecular markers for the classification of cytologically indeterminate thyroid nodules. Journal of endocrinological investigation. 2020 Jun:43(6):703-716. doi: 10.1007/s40618-019-01164-w. Epub 2019 Dec 18 [PubMed PMID: 31853887]
Stang MT, Armstrong MJ, Ogilvie JB, Yip L, McCoy KL, Faber CN, Carty SE. Positional dyspnea and tracheal compression as indications for goiter resection. Archives of surgery (Chicago, Ill. : 1960). 2012 Jul:147(7):621-6. doi: 10.1001/archsurg.2012.96. Epub [PubMed PMID: 22430090]
Level 2 (mid-level) evidencePolistena A, Sanguinetti A, Lucchini R, Galasse S, Monacelli M, Avenia S, Triola R, Bugiantella W, Rondelli F, Cirocchi R, Avenia N. Surgical approach to mediastinal goiter: An update based on a retrospective cohort study. International journal of surgery (London, England). 2016 Apr:28 Suppl 1():S42-6. doi: 10.1016/j.ijsu.2015.12.058. Epub 2015 Dec 18 [PubMed PMID: 26708863]
Level 2 (mid-level) evidenceMercante G, Gabrielli E, Pedroni C, Formisano D, Bertolini L, Nicoli F, Valcavi R, Barbieri V. CT cross-sectional imaging classification system for substernal goiter based on risk factors for an extracervical surgical approach. Head & neck. 2011 Jun:33(6):792-9. doi: 10.1002/hed.21539. Epub 2010 Aug 24 [PubMed PMID: 20737483]
Level 2 (mid-level) evidenceCoskun A, Yildirim M, Erkan N. Substernal goiter: when is a sternotomy required? International surgery. 2014 Jul-Aug:99(4):419-25. doi: 10.9738/INTSURG-D-14-00041.1. Epub [PubMed PMID: 25058777]
Level 2 (mid-level) evidenceTaniguchi T, Suzuki M. Postoperative laryngeal granuloma in mediastinal goitre with gastro-oesophageal reflux disease. BMJ case reports. 2024 Sep 24:17(9):. doi: 10.1136/bcr-2023-258916. Epub 2024 Sep 24 [PubMed PMID: 39317485]
Level 3 (low-level) evidence