Continuing Education Activity

This activity describes indications and techniques of thyroidectomy and reviews the role of the healthcare team in evaluating and treating patients who undergo thyroidectomy. Partial or complete thyroidectomy is performed to relieve compressive symptoms of thyroid hypertrophy, prevent sequelae of thyroid carcinoma, and achieve hormonal control of hyperthyroidism. The main indications include symptomatic benign thyroid goiter, thyroid carcinoma, and hyperthyroidism refractory to medical therapy. Open approaches remain most common, although robotic approaches have been utilized successfully. This activity reviews the evaluation and treatment of thyroid nodules and highlights the role of the healthcare team in evaluating and treating this condition.

Objectives:

• Describe the indications of thyroidectomy.
• Review the management of benign and malignant thyroid disease.
• Identify the most common adverse events associated with thyroidectomy.

Introduction

Thyroidectomy is a well-described procedure used to excise the thyroid gland. It is a common procedure in modern medicine and may be used to treat malignancy, benign disease, or hormonal disease that is not responsive to medical management.[1]

The delicate anatomy of the anterior neck, the critical nature of adjacent structures, and tight working spaces make thyroidectomy a challenging procedure to perform safely and effectively. Thyroidectomy, as a procedure, has developed as the anatomic understanding and surgical approaches have evolved. In the 1870s, Billroth and Kocher pioneered the classic thyroidectomy and reported a mortality rate of 8%, a significant success at the time.[2] By the time Theodor Kocher was awarded the Nobel Prize in 1909, mortality rates had fallen to less than 1% for his development of the surgery. 

While the general tenets of the surgery have remained the same, improvements in technique, diagnostics, understanding of relative anatomy, anesthesia techniques, and technology have allowed thyroidectomies to become a standard, effective, and safe procedure throughout most of the world with a mortality far, far, below that landmark 1% from Kocher's time.[2]

Anatomy and Physiology

The thyroid gland is an endocrine gland that secretes thyroid hormone, a regulatory hormone with multiple critical physiologic functions. Hypothyroid and hyperthyroid states both produce a relatively non-specific constellation of symptoms, and thyroid malfunction is a consideration in the differential diagnosis for a similarly long list of symptoms. Nevertheless, hypothyroidism is classically described as producing cold intolerance, dry skin, lethargy, constipation, pretibial edema, and weight gain.[3] Hyperthyroidism is classically associated with weight loss, heat intolerance, osteoporosis, muscle weakness, muscle tremor, brittle hair or hair loss, and atrial fibrillation.[4] Adjacent to the thyroid gland are four parathyroid glands whose primary function is the regulation of serum calcium levels via secretion of parathyroid hormone (parathermone, PTH).[5] 

The thyroid gland is situated in the anterior neck and is invested within the middle layer of the deep cervical fascia. It is bound laterally by the carotid arteries, posteriorly by the pre-tracheal fascia and trachea, and anteriorly by the strap muscles. The right and left thyroid lobes are anterior and lateral to the trachea, joined at the midline by the thyroid isthmus. The pretracheal fascia affixes the thyroid between the 2nd and 3rd tracheal rings in most patients.[6] Additionally, between 15-75% of patients have an embryologic remnant coursing superiorly from the thyroid isthmus known as the pyramidal lobe. The lobe may be as small as 3mm or as large as 6cm.[7] The pyramidal lobe may be solely attached to the thyroid or may extend superiorly to attach to the thyroid cartilage or hyoid bone. Notably, the presence of a pyramidal lobe is often not appreciated on pre-operative imaging.[7]

In the immediate vecinity of the thyroid gland are the parathyroid glands, which can be identified by their brownish-yellow hue as compared to the yellow hue of fat globules. The superior parathyroid glands are classically found near the posterolateral aspect of the superior pole approximately 1 cm superior to the intersection of the recurrent laryngeal nerve (RLN) and the inferior thyroid artery (ITA). The inferior parathyroid glands are described as being located adjacent to the inferior aspect of the thyroid lobe between the inferior thyroid artery and vein.[5] Importantly, the inferior parathyroid glands are ventral (anterior to) the plane of the recurrent laryngeal nerve, though their location is more variable than the superior glands. The superior parathyroid glands are dorsal (posterior to) the plane of the nerve. In a small but significant number of patients, ectopic and/or supra-numerary parathyroid glands exist, and these can be located anywhere from the inferior border of the mandible to the mediastinum.[8] 

The thyroid gland's prominent blood supply is from the superior thyroid artery, which is the first branch off of the external carotid artery, as well as the inferior thyroid artery branching off of the thyrocervical trunk. Ten percent of patients have an additional unpaired artery, the thyroidia ima artery, via the thyrocervical trunk. Venous drainage occurs into the internal jugular vein via the superior and middle thyroid veins bilaterally, and into the brachiocephalic veins via the inferior thyroid veins bilaterally, though ectopic drainage via anterior thyroid veins is not uncommon.[6]

The vagus nerve gives off two branches bilaterally, the superior and the recurrent laryngeal nerves (RLN), which are most clinically relevant during thyroid surgery. The recurrent laryngeal nerve, later branching off cranial nerve X, travels distally and takes a recurrent proximal course. On the right side, the RLN loops around the subclavian artery, and on the left side, it loops around the aortic arch and courses proximally towards the thyroid gland. The recurrent laryngeal nerves run deep to the gland and are at risk of injury during thyroidectomy. The right recurrent laryngeal nerve runs at a more oblique angle as compared to the left due to its course around the right subclavian artery.[8] The left recurrent laryngeal nerves tend to take a more straight course within the tracheoesophageal groove. The RLN classically enters the thyroid posterior to the cricothyroid joint and can be found in close proximity to the superior parathyroid gland. The RLN can be found to have extra laryngeal divisions (often splitting into sensory and motor divisions in these patients) between 35% to 80% of the time requiring caution during dissection to avoid unintentional division of a branch of the RLN.[6]

An important variation in RLN anatomy is an anomalous or nonrecurrent RLN. A non-recurrent nerve occurs in less than 1% of patients (between 0.3% to 0.8%).  It is most common on the right side when the subclavian artery anatomy is also anomalous. A retro esophageal subclavian artery is the most common etiology, which is associated with dysphagia lusoria. A left-sided nonrecurrent nerve is more rare, due to its predominant course of looping around the aortic arch.[6]

An additional nerve of importance is the external branch of the superior laryngeal nerve (SLN). This nerve runs superior to the superior thyroid artery in 80% of cases, and inferior to it 20% of the time. The SLN branches into external and internal branches approximately 1.5 cm caudal to the carotid bifurcation. Although the SLN is often not always identified during thyroidectomy, care should be taken to be in close proximity to the superior pole when ligating the superior thyroid artery.[9]

Indications

Thyroidectomy may be performed for a number of benign and malignant conditions including thyroid nodules, hyperthyroidism, obstructive or substernal goiter, differentiated (papillary or follicular) thyroid cancer, medullary thyroid cancer (MTC), anaplastic thyroid cancer, primary thyroid lymphoma (surgery is limited to obtaining tissue biopsy), and metastases to the thyroid from extrathyroidal primary cancer (most commonly renal cell and lung cancer). 

Thyroid nodules are a worldwide phenomenon present clinically in 1% of men and 5% of women. The majority of nodules are benign, with only 5% of nodules representing cancer. With high-resolution ultrasound, thyroid nodules can be detected in up to 68% of randomly selected subjects who receive a screening ultrasound, with a predilection towards women and the elderly.[1]

Goiter is described as an abnormal growth of the thyroid gland and can be diffuse or nodular. The presence of goiter can be linked to iodine deficiency and is therefore endemic in iodine-deficient regions of the world. In asymptomatic, iodine-deficient groups, a goiter can be diagnosed in approximately a quarter of the population, with increasing frequency in older populations.[10] However, the majority will not become surgical candidates or develop thyroid nodules requiring intervention. 

Goiter may also occur in regions where significant iodine deficiency does not exist. In these regions, goiter is typically multi-nodular and may be secondary to autoimmune disorders of the thyroid, such as Hashimoto's thyroiditis or Graves' disease. 

Thyroidectomy is potentially indicated in both malignant and benign pathologies with a high level of selectivity. Indications include thyroid cancer, toxic multinodular goiter, toxic adenomas, goiter with compressive symptoms, Graves disease that is either not responsive to medical treatment or for whom medical management may not be advised, such as those attempting to become pregnant.

Most thyroid nodules will not require excision. Nodules that are at increased risk of malignancy will often require fine needle aspiration (FNA) to aid in the differentiation between benign and malignant nodules. When nodules are of a size greater than 1 cm, non-functional (known as a "cold" nodule), and/or displaying concerning ultrasound findings, they will generally meet the criteria for biopsy.[1] Numerous societies have released treatment algorithms for the management of thyroid nodules. The American Thyroid Association guidelines stress two parameters: size of the nodule and sonographic pattern. 

American Thyroid Association Guidelines[11]

Initial Evaluation

• Serum TSH (if low, scintigraphy indicated)
• Incidental increased uptake on scintigraphy in a nodule >1cm warrants FNA

Sonographic Pattern

• Benign pattern (0% risk of malignancy) - no biopsy indicated
• Very low suspicion pattern (<3% risk of malignancy) - biopsy if > or = 2cm in size. Serial ultrasound also acceptable.
• Low suspicion pattern (5-10% risk of malignancy) - biopsy if > or = 1.5cm in size.
• Intermediate suspicion pattern (10-20% risk of malignancy) - biopsy if > or = 1cm in size
• High suspicion pattern (70-90% risk of malignancy) - biopsy if > or = 1cm in size

Historically, thyroidectomy was the treatment of choice for goiter. Improvements in diagnostic imaging and medical management have reduced the need for thyroidectomy for most goiters and many thyroid nodules with benign characteristics. Furthermore, the high frequency of thyroid nodules has provided abundant research used to determine which characteristics of a thyroid nodule require surgery versus observation, protecting many patients from the risk of unnecessary thyroid surgery.In differentiated thyroid cancer, such as papillary thyroid cancer (PTC), lobectomy may be performed for microcarcinoma. Indications for total thyroidectomy rather than lobectomy in PTC include size >1cm, tall cell variants, extrathyroidal extension, bilateral disease, and lymphovascular invasion[12]. Assessment of regional lymph nodes should be performed on any thyroid ultrasound, and FNA considered for any enlarged or abnormal nodes in the setting of known or suspected thyroid malignancy[13].

Contraindications

There are few true contraindications to thyroidectomy. Given that thyroid cancer is generally a slowly progressive disease, the risk/benefit profile changes with age and this should be discussed with patients who are considering undergoing thyroidectomy. 

Anaplastic carcinoma represents a treatment dilemma due to its poor outcomes and propensity for rapid progression.[14] Surgical resection may be offered if gross total resection can be achieved with minimal morbidity and there is no evidence of metastases. Surgical intervention may otherwise be contraindicated.[15]

Surgical factors considered relative contraindications to outpatient surgical management include massive goiter, extensive substernal goiter, locally advanced carcinoma, challenging hemostasis, and a difficult thyroidectomy in the setting of Hashimoto's or Graves' disease.[16] 

Equipment

• Head and neck soft-tissue tray
• Recurrent laryngeal nerve monitoring endotracheal tube (if using)
• Nerve monitor or nerve stimulator (if using)
• Sutures and/or hemostatic clips per the surgeon's preference
• Advanced energy device such as Shaw Scalpel or Harmonic Scalpel (if using)

Personnel

Thyroidectomy requires an operating surgeon, a surgical assistant, an operating room nurse, and an anesthetist. If available, a second surgical assistant is valuable for retraction.

Preparation

Thyroid imaging: ultrasonography is the gold standard for initial thyroid imaging. Additional imaging modalities such as computed tomography (CT) or magnetic resonance imaging are utilized in select cases to define the extent in advanced disease. Positron emission tomography can be utilized in the presence of aggressive thyroid cancer such as anaplastic carcinoma or advanced or recurrent papillary thyroid carcinoma. A chest CT scan can be useful in determining the likelihood that a sternotomy approach would be required in the event of thyroid extending below the thoracic inlet. Factors associated with the need for sternotomy include the extension of the nodule beyond the aortic arch or into the posterior mediastinum, presence of mediastinal nodal disease, capsular calcification (implying difficult soft tissue dissection), and conical shape to the goiter. Even with these risk factors, sternotomy is very rarely needed.[17]

Laboratory testing: All patients require a serum thyroid-stimulating hormone (TSH) level to determine preoperatively whether the patient is euthyroid, hyperthyroid, or hypothyroid. In patients with serologic evidence of hyperthyroidism, thyrotropin receptor antibodies (TRAb) should be obtained to evaluate for Graves disease.[4] If the TRAb is negative with a nodule or nodules present on ultrasound, thyroid scintigraphy should be obtained to evaluate for a toxic adenoma or a toxic multinodular goiter.[4] In the presence of hypothyroidism, thyroid peroxidase antibodies (TPO) may be obtained to evaluate for the presence of Hashimoto thyroiditis. For those with suspected medullary thyroid cancer, testing may include calcitonin, carcinogenic embryonic antigen (CEA), genetic testing for medullary thyroid cancer as in multiple endocrine neoplasia type 2 (MEN2A or MEN2B). 

Laryngeal examination: injury to the recurrent laryngeal nerve (RLN) during thyroid surgery can result in vocal cord paresis or paralysis. Pre-operative assessment of the voice is recommended, with consideration given to dedicated, flexible fiberoptic laryngoscopy if voice abnormalities are identified.[1] Outpatient thyroidectomy is generally considered safe for selected patients and an experienced surgeon, but ultimate disposition is at the discretion of the operating surgeon.[16]The patient is positioned supine on the operating table, and general anesthesia is induced. The patient is intubated with a nerve-monitoring endotracheal tube (ETT) if such monitoring technology is planned. The ETT should be positioned properly with the recurrent laryngeal nerve monitoring sensors located between the vocal cords, and function of the monitor confirmed after intubation in accordance with the device manufacturer's instructions. 

The patient is then positioned with the neck hyperextended, a shoulder roll may be placed to facilitate this position. Depending on the surgeon's preference, the head may be secured to the bed with tape/padding. Extending the neck and placing the head on a donut cushion will also help with operative exposure. The neck is palpated for the identification of anatomic landmarks, including the thyroid cartilage, cricoid cartilage, thyroid lobes, and sternal notch. The anatomic midline is marked using the sternal notch and the mandible as landmarks. The cricoid cartilage and thyroid notch are marked. A surgical incision is marked in a natural skin crease, if possible, approximately 2 centimeters above the sternal notch.[8] A typical incision is 4-6 centimeters in length; longer incisions may be appropriate for the removal of large thyroids or if concurrent lateral neck dissection is indicated. The neck is then prepared with surgical scrub, and the patient is draped, taking care to leave the anatomic markings in the field of view.

A recurrent laryngeal nerve monitor is connected to the leads from the ETT and confirmed to be functioning if such monitoring technology is being used. The ETT provides EMG feedback from the vocalis muscles in order to monitor the function of the RLN. The monitor may alarm when changes in nerve output to the vocalis muscles change or when the surgeon uses a nerve probe to stimulate the RLN.  83% to 85% of patients with loss of signal intraoperatively will have postoperative vocal cord paresis or paralysis.[18][19] 

Technique or Treatment

An incision is made through the skin, subcutaneous tissue, fat, and platysma. Skin flaps are then raised deep to the platysma and superficial to the sternohyoid muscle. The flaps are elevated superiorly and inferiorly to the level of the thyroid cartilage and sternal notches, respectively. Care should be taken to identify and preserve the anterior jugular veins as well as the superficial network of veins that lie beneath the platysma to avoid unnecessary bleeding. 

The strap muscles (sternohyoid and sternothyroid) are lateralized by incising the median raphe until the thyroid capsule is identified. During the removal of a large multi-nodular goiter, the strap muscles may rarely require the horizontal division to improve exposure. If the division of these muscles is necessary, it should take place as high as possible to preserve the strap muscles' innervation by the ansa cervicalis.[20]

In a total thyroidectomy, it is prudent to begin the procedure on the side of a confirmed malignant diagnosis or on the larger side in benign disease. In the event of an intra-operative complication or nerve injury requiring early termination of the procedure, this allows the removal of the most important tissue prior to termination of the surgery. It should be noted that there are many approaches to thyroidectomy, and only one is described in detail below. 

Blunt dissection of the superficial loose areolar tissue off of the thyroid gland progresses laterally until the carotid sheath is identified.[21] This can be done by careful finger dissection, or with retraction and bipolar cautery of the tissue. This defines the lateral extent of dissection. The lobe is gently displaced toward the midline, and the middle thyroid vein is identified, ligated, and divided (this is sometimes performed after both poles are addressed). The lobe is then retracted anteromedially to expose the superior thyroid artery and vein. Once these are skeletonized, they are ligated and divided as close to the gland as possible to avoid injury to the superior laryngeal nerve (SLN). Some surgeons prefer to definitively identify the SLN in all thyroidectomies. During this dissection, care should be taken to identify and preserve the superior parathyroid glands. The inferior thyroid vein is next ligated and divided as it approximates the thyroid after the identification of the inferior parathyroid glands. The lobe is then retracted medially, and the recurrent laryngeal nerve is identified. 

The recurrent laryngeal nerve is nearly always located within a few millimeters of the inferior thyroid artery but may be superficial or deep to it.[22] It should be noted that as the gland is pulled anteriorly and medially to facilitate dissection of the nerve, this maneuver pulls the nerve onto the body of the thyroid such that it can form a genu. Once the nerve is identified and released, it drops down into its anatomic location. Once identified, the nerve can be gently dissected, as necessary, to its entry point into the larynx at the level of the cricothyroid joint while dissecting the thyroid lobe free from the recurrent laryngeal nerve. During the search for the recurrent laryngeal nerve, parathyroid glands can also serve as landmarks. The superior gland will classically be found along the posterior aspect of the thyroid capsule in a plane deep (dorsal) to the plane of the RLN. The inferior glands are more variable in location but are expected to be anterior (ventral) to the plane of the RLN. Once these structures have been identified and preserved, the gland can be elevated off the trachea, and Berry's ligament can be divided or cauterized with bipolar cautery to free the gland. The ligament of Berry should be divided as close to the trachea as possible, with care not to enter the trachea. The gland should be elevated to the midline. In a hemithyroidectomy, the isthmus can be tied off with a surgical tie or divided with a device such as a harmonic scalpel. In a total thyroidectomy, the initially dissected lobe can be removed to increase the working space in the neck or left in situ such that the entire thyroid can be removed en bloc.[22] 

The surgeon may consider sending intraoperative frozen sections in select circumstances. Given advances in molecular testing, frozen sections have less utility in Bethesda criteria 3 and 4 nodules. They may be considered in Bethesda 5 nodules (suspicious for malignancy) in order to determine if a completion thyroidectomy should be performed, especially in elderly patients or those with comorbidities, and noncompliant patients with surgeon concern for follow-up.[23] 

Prior to closure, the surgical field is evaluated for hemostasis. The divided strap muscles and platysma are re-approximated with absorbable suture such as 3-0 Vicryl followed by re-approximation of the skin. Many surgeons prefer to place a drain in order to monitor and trend output. Drains placed post thyroidectomy with neck dissection can also be useful in monitoring for chyle leak, which may give the drain a milky appearance. 

Intraoperatively, if a parathyroid gland is found to be devascularized, it should be re-implanted to minimize the chance of postoperative hypoparathyroidism.[24] Prior to re-implantation, a small section of the specimen can be evaluated by pathology with a frozen section to confirm the tissue is indeed parathyroid tissue. Alternatively, the specimen can be placed in a small cup of saline. Fat will float while parathyroid tissue will often sink due to its higher density.[25] The gland should then be morselized and implanted in an adjacent sternocleidomastoid or strap muscle. A surgical clip should be placed over the re-implantation pocket to mark it. This allows for easier identification if the patient develops hyperparathyroidism at a later date, and removal of the specimen is required. If a parathyroid gland appears grossly enlarged intraoperatively compared to the other parathyroid glands, and if there is suspicion for a parathyroid adenoma, an intraoperative PTH level may be drawn. The surgeon may then choose to resect the suspicious parathyroid gland. A portion of this gland may be sent for a frozen section to confirm its pathology prior to resection. 

Central neck dissection, in conjunction with total thyroidectomy, is sometimes indicated. CND should be performed with well-differentiated large tumors (T3 and T4), poorly differentiated thyroid cancers, and the presence of pathologic lymph nodes in the central compartment.[26] Lateral neck dissection (LND) is not performed prophylactically. Indications for bilateral LND include MTC with high calcitonin and MTC with palpable cervical lymphadenopathy. Indications for ipsilateral LND include sporadic MTC 2 cm or larger with evidence of central neck disease or grossly identifiable lateral neck disease in PTC or MTC.[26]

Complications

• Hemorrhage: severe cases may cause airway compression and be life-threatening
• Hypoparathyroidism: results in hypocalcemia which may become symptomatic and life-threatening if unrecognized/untreated. Up to 1/3 of patients undergoing total thyroidectomy will have at least transient hypocalcemia postoperatively. It is important to maintain a consistent protocol for calcium management after total or completion thyroidectomy to minimize related complications.[27] 
• Injury to the recurrent laryngeal nerve: results in hoarseness and potentially aspiration. This is most commonly temporary but may be permanent <1% of cases. 
• Injury to the superior laryngeal nerve: results in voice pitch change. Reported rates of injury range from 0% to 58%.[28]
• Post-surgical infection: approximately 6% of cases.
• Esophageal injury
• Tracheal injury
• Horner syndrome
• Dysphagia
• Chyle leak

Clinical Significance

Thyroidectomy is an important surgical procedure with high-quality evidence for the management of benign and malignant thyroid disease.[1] Due to the close proximity of several critical anatomic structures, safe thyroidectomy requires detailed anatomic knowledge and careful patient selection is paramount.

Enhancing Healthcare Team Outcomes

Rates of thyroid nodule detection are rapidly increasing worldwide.[1] The majority of nodules are incidentally found, asymptomatic, and represent benign disease. They are palpable in 1-5% of patients, but clinically appreciable on imaging in at least 19% of the general population. Of the 7-15% of nodules that do represent malignancy, greater than 90% represent differentiated thyroid carcinoma, which has excellent survival outcomes.[1] As such, optimal management of the thyroid nodule is a topic of significant debate. Furthermore, there are many available treatment options and protocols, which include observation, serial imaging, hemithyroidectomy, and total thyroidectomy. On this basis, optimal management of thyroid nodules is a complex topic that requires understanding the latest guidelines.[29]

Pre-operative workup must be thorough with an emphasis placed on shared decision making with the patient and understanding of the latest surgical guidelines. Workup should include imaging, laboratory workup, tissue sampling, and possibly the use of molecular markers to stratify the risk of the disease process. Additionally, a comprehensive team of providers, including a surgeon, endocrinologist, pathologist, and radiologist, should be involved in the care of the patient. The teams should work together to perform the pre-operative workup and postoperative management, including the use of hormone replacement therapy and radioactive iodine ablation when indicated. Once the teams have coordinated their efforts, their findings should be discussed with the patient with potential treatment options presented. Patients may ultimately have to rely upon their own value system and preferences in deciding between an upfront total thyroidectomy vs. a hemithyroidectomy with the possibility of completion thyroidectomy depending on final pathology. Taken together, the care of the patient with a thyroid nodule is complex and multi-disciplinary in nature, reliant upon shared decision making, and requires a thorough understanding of the literature.