Differentiated thyroid cancer: Surgical treatment

INTRODUCTION — The primary therapy for differentiated (papillary and follicular) thyroid cancer is surgery. Considerable controversy exists about how much thyroid tissue should be removed at the initial operation, and there are no prospective randomized clinical trials to provide guidance for selection of the optimal operation.

This topic will review the rationale behind selection of the most appropriate type of operation for these patients, the basic approaches to the operation, and management of the medical complications of surgery, particularly hypoparathyroidism. The technique of thyroidectomy and staging of thyroid cancer, as well as an overview of the management of differentiated thyroid cancer, radioiodine treatment, and external radiotherapy, are discussed separately.

●(See "Thyroidectomy".)

●(See "Differentiated thyroid cancer: Clinicopathologic staging".)

●(See "Differentiated thyroid cancer: Overview of management".)

●(See "Differentiated thyroid cancer: Radioiodine treatment".)

●(See "Differentiated thyroid cancer: External beam radiotherapy".)

IMPORTANCE OF PREOPERATIVE IMAGING — We suggest preoperative ultrasound evaluation of the central and lateral neck lymph nodes for all patients with malignant cytological findings on the fine-needle aspiration (FNA). Preoperative ultrasonography of the central and lateral neck identifies abnormal lymph nodes in as many as 20 to 30 percent of patients [1,2]; these ultrasound findings may alter the planned surgical procedure in up to 20 percent of patients [3,4]. However, ultrasonography can miss as many as 50 percent of the involved lymph nodes in the central neck because the overlying thyroid gland hinders adequate visualization [5].

While ultrasonography is the preferred modality for evaluation of the thyroid and cervical lymph nodes, alternative imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT) with contrast, laryngoscopy, and endoscopy may be required in patients with potentially more advanced local disease in order to accurately define the extent of tracheal, nodal, esophageal, laryngeal, or vascular involvement [6]. Additional imaging beyond routine preoperative neck ultrasonography should be obtained in patients presenting with locally advanced disease, as manifested by:

●Clinically palpable metastatic lymphadenopathy or other evidence of extensive lymph node involvement identified preoperatively, as these patients may have nodal involvement in regions inadequately evaluated with ultrasound (mediastinal, infraclavicular, retropharyngeal, or parapharyngeal lymph node chains)

●Signs or symptoms of locally invasive disease:

•Dysphagia

•Respiratory compromise

•Hemoptysis

•Rapid tumor enlargement

•Changes in voice

•Vocal cord paralysis

•Tumor fixed to surrounding structures

•Ultrasonographic evidence of macroscopic extrathyroidal extension

In these locally advanced cases, we routinely obtain preoperative CT of the neck and chest with intravenous contrast to evaluate these lymph node chains and optimize surgical planning. In such cases, the benefit of accurate surgical planning outweighs the delay in radioiodine administration that is necessary after the use of iodinated contrast. Fludeoxyglucose-positron emission tomography (FDG-PET) scanning is seldom used in preoperative surgical planning.

APPROACH TO THYROIDECTOMY

Types of procedures — There are two potential surgical approaches to differentiated thyroid cancer: total (or near-total) thyroidectomy and unilateral lobectomy and isthmusectomy. A third option, subtotal thyroidectomy, is considered to be an inadequate procedure and is not recommended.

●Total thyroidectomy involves removal of all thyroid tissue while attempting to identify and preserve the recurrent laryngeal nerve (RLN), the superior laryngeal nerve (SLN), and the vascular supply to the parathyroid glands.

Near-total thyroidectomy is identical except for a slightly more conservative approach to preserving the posterior thyroid capsule of the lobe contralateral to the thyroid tumor.

●A unilateral lobectomy and isthmusectomy involves removal of one entire lobe and the isthmus, without entering the contralateral neck.

The difference between total and near-total thyroidectomy procedures is primarily a semantic one because most patients who undergo radioiodine imaging after total thyroidectomy have thyroid-bed uptake consistent with residual normal thyroid tissue. Whether there is a clinically important difference between total thyroidectomy and near-total thyroidectomy is uncertain. This was illustrated by the results of an analysis of 23,605 patients from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database with median follow-up of 6.6 years [7]. In a multivariate analysis adjusted for prognostic variables (ie, older age, larger tumors with extrathyroidal extension), the absolute difference in 10-year overall (0.9 percent) and cause-specific (0.2 percent) survival favored total thyroidectomy, but the difference, although statistically significant, was small and of uncertain clinical significance.

If total thyroidectomy is indicated, an experienced thyroid surgeon is unavailable, and it is impossible to refer the patient elsewhere, then the slightly more conservative "near-total" procedure should be performed. In addition, a surgeon intending to perform a total thyroidectomy for more extensive disease may choose to stop with a unilateral lobectomy and isthmusectomy if the RLN has been damaged or intentionally sacrificed during the resection of the initial lobe. The patient should subsequently be referred to a specialist for completion of thyroidectomy [8].

Subtotal thyroidectomy, in which several grams of thyroid tissue are preserved along the posterior capsule bilaterally, is an inadequate procedure for patients with thyroid cancer. It is associated with a higher complication rate if subsequent surgery is required, and we do not recommend it [9-11].

Choice of procedure — Given access to an experienced thyroid surgeon, we suggest the following procedures for patients with papillary or follicular cancer.

●Tumor <1 cm without extrathyroidal extension and no lymph nodes – When surgery is planned for unilateral intrathyroidal differentiated thyroid cancer <1 cm, a thyroid lobectomy is the preferred approach unless there are clear indications to remove the contralateral lobe (eg, clinically evident thyroid cancer in the contralateral lobe, previous history of head and neck radiation, strong family history of thyroid cancer, or imaging abnormalities that will make follow-up difficult).

●Tumor 1 to 4 cm without extrathyroidal extension and no lymph nodes – For intrathyroidal tumors between 1 and 4 cm, the initial surgical procedure can either be a total thyroidectomy or thyroid lobectomy. Total thyroidectomy would be chosen either based on patient preference, the presence of ultrasonographic abnormalities in the contralateral lobe (nodules, thyroiditis in the contralateral lobe, or nonspecific lymphadenopathy, which will make follow-up difficult), or on a decision by the treatment team that radioiodine therapy may be beneficial either as adjuvant therapy or to facilitate follow-up.

●Tumor ≥4 cm, extrathyroidal extension, or metastases – Total thyroidectomy is recommended if the primary tumor is 4 cm in diameter or greater, there is extrathyroidal extension of tumor, or there are metastases to lymph nodes or distant sites.

●Any tumor size and history of childhood head and neck radiation – Total thyroidectomy should also be performed in all patients with thyroid cancer who have a history of exposure to ionizing radiation of the head and neck, given the high rate of tumor recurrence with lesser operations in these patients [12]. (See "Radiation-induced thyroid disease".)

●Multifocal papillary microcarcinoma (fewer than five foci) – Unilateral lobectomy and isthmusectomy is an appropriate procedure for patients whose pathology reports subsequently show multifocal papillary microcarcinomas with fewer than five foci.

●Multifocal papillary microcarcinoma (more than five foci) – When multifocal papillary cancer is appreciated preoperatively, particularly when a large number of microcarcinoma are suspected (eg, greater than five foci, especially if the foci are in the 8 to 9 mm size range), we are more likely to perform a total thyroidectomy.

For patients whose initial procedure was a lobectomy and in whom pathology shows multifocal papillary microcarcinomas with more than five foci, especially if the foci are in the 8 to 9 mm range, we typically refer patients for completion thyroidectomy.

●Indeterminate or suspicious thyroid nodules – For patients with a cytologically indeterminate nodule (Bethesda III or IV), a unilateral lobectomy and isthmusectomy is usually performed unless mutational testing suggests the nodule is likely to be benign. Because as many as 60 percent of these patients may prove to have benign disease, total thyroidectomy is usually not required as the initial procedure [13]. If the final pathologic diagnosis is cancer and if a completion thyroidectomy is needed (for example, to administer radioiodine), it can be performed without significant increased risk because the second surgery would avoid the first operative field [14,15]. This occurs most commonly in patients with follicular cancer or follicular variant papillary cancer [15].

For patients with a cytologically suspicious nodule (Bethesda V), the choice between a lobectomy and a total thyroidectomy is less clear, since the risk of malignancy may exceed 80 percent, especially if mutational testing is positive. Additional clinical characteristics and patient preference should help determine the extent of surgery. (See "Diagnostic approach to and treatment of thyroid nodules", section on 'Management'.)

Most patients with clinically significant (tumor >4 cm, extrathyroidal extension, clinically apparent metastatic disease to nodes) papillary and follicular thyroid cancer are best served by total (or near-total) thyroidectomy. The benefit of total or near-total thyroidectomy in this subset of patients comes from the National Thyroid Cancer Treatment Cooperative Study Group in 2006 [16]. In a multicenter analysis of outcomes of nearly 3000 patients with differentiated thyroid cancer, significantly worse overall survival was reported in the following groups of patients who underwent less-than-total or near-total thyroidectomy (with risk ratios for all-cause mortality in subgroups ranging from 1.36 to 1.76):

●Papillary cancer under age 45 years, with tumor greater than 4 cm, or in the presence of macroscopic extrathyroidal extension or extracervical metastases

●Papillary cancer at age ≥45 years, with tumor of at least 1 cm, or in the presence of multifocal tumors, extrathyroidal extension, or metastases to locoregional nodes or distant sites

●Follicular cancer under age 45 years, with tumor greater than 4 cm, or in the presence of macroscopic multifocality, macroscopic invasion of either the tumor capsule or extrathyroidal tissues, poor differentiation, or extracervical metastases

●Follicular cancer at age ≥45 years

Additional data from the 2009 National Thyroid Cancer Treatment Cooperative Study Group demonstrated a lower recurrence rate in patients with multifocal, microscopic papillary cancer who had a total or near-total thyroidectomy (6 versus 18 percent in those undergoing less than near-total thyroidectomy) [17].

In properly selected patients with low-risk disease, however, thyroid lobectomy is an acceptable alternative to total thyroidectomy [6,18]. While the National Comprehensive Cancer Network (NCCN) guidelines have accepted lobectomy for intrathyroidal low-risk differentiated thyroid cancers up to 4 cm in size for many years [18], the American Thyroid Association (ATA) guidelines have previously recommended total thyroidectomy for all tumors greater than 1 cm. However, the 2015 ATA guidelines endorsed thyroid lobectomy as sufficient initial treatment in properly selected patients with intrathyroidal primary tumors as large as 4 cm, provided that the patient and clinical team agree that a more extensive surgery is not required for adjuvant therapy or to facilitate follow-up [6].

This renewed interest in thyroid lobectomy is the result of newer observational data [7,19-23] reexamining the survival benefit previously attributed to total thyroidectomy [24-28] in patients with intrathyroidal tumors. In properly selected patients, clinical outcomes are very similar following unilateral or bilateral thyroid surgery. As an example, in an analysis from the NCI SEER database, patients treated with lobectomy had a 10-year overall survival (90.8 percent) and cause-specific survival (98.6 percent) that was nearly identical to patients selected to receive total thyroidectomy (90.4 and 96.8 percent, respectively) [7]. A greater proportion of patients who were treated with lobectomy had smaller tumor size ≤2 cm (65 versus 53 percent) without extrathyroidal extension, suggesting that the appropriate selection of candidates for lobectomy is important for achieving good outcomes. In addition, there are fewer complications with unilateral surgery, even among high-volume surgeons [8].

Additional support for thyroid lobectomy in patients with intrathyroidal tumors is related to:

●The marked increase in diagnosis and treatment of very-low-risk thyroid cancers

●A trend toward a risk-adapted, individual management approach in thyroid cancer

●Recommendations calling for more selective use of radioiodine as ablation or adjuvant therapy in intrathyroidal tumors (<4 cm)

●A decrease in the use of radioiodine scanning as a routine test in follow-up

●Routine use of neck ultrasonography as the primary follow-up imaging modality

●A better understanding of how serum thyroglobulin (Tg) can be used in follow-up of patients that did not undergo radioiodine ablation

As a result of these changes, clinicians will be evaluating an increasing number of thyroid cancer patients that will be potential candidates for thyroid lobectomy. It is important for patients to understand that even if the preoperative decision is to proceed with a thyroid lobectomy, there are intraoperative findings (eg, identification of metastatic lymph nodes, invasion into surrounding structures) that could necessitate immediate conversion to a total thyroidectomy. Thus, patients are encouraged to empower the surgeon to make the decision to proceed with total thyroidectomy if clinically indicated. Furthermore, findings on the final histology examination obtained several days after lobectomy may necessitate a completion thyroidectomy in 5 to 20 percent of patients, depending on the preferences of the patient and treatment team with regard to need for radioactive iodine therapy, additional staging information, or highly sensitive follow-up studies [22,29-35].

Surgical technique — Knowledge of the surgical technique of thyroidectomy allows the referring clinician to interpret operative reports and findings, understand the particular risks of thyroidectomy, and explain to the patient what lies ahead [10,11]. The technique of thyroidectomy is reviewed in detail elsewhere. (See "Thyroidectomy".)

Preservation recurrent laryngeal nerve — Identification and preservation of the RLN and SLN are the major technical challenges of this procedure (figure 1). Indications for preoperative laryngeal exam and intraoperative nerve monitoring are reviewed elsewhere. (See "Thyroidectomy", section on 'Laryngeal examination' and "Thyroidectomy", section on 'Intraoperative nerve monitoring'.)

Parathyroid glands — In addition to identifying the RLN and SLN, normal variations in the location and number of the parathyroid glands must be appreciated to avoid postoperative hypoparathyroidism (figure 2). (See "Surgical anatomy of the parathyroid glands" and "Thyroidectomy", section on 'Parathyroid preservation'.)  

●Most superior parathyroid glands are located within 1 cm of the intersection of the RLN and the inferior thyroid artery, usually within the thyroid fascia. Approximately 15 percent are located within the thyroid capsule, and the remainder are located in the retropharyngeal or retroesophageal spaces.

●The location of the inferior glands is far more variable, although they are usually anterior and lateral to the recurrent nerves. They may be just below the superior glands, posterolateral to the lower pole of the thyroid; immediately inferior or posterior to the thyroid; within or below the thymus; or in the posterior mediastinum.

●The arterial supply for the parathyroid glands is usually provided by branches of the inferior thyroid artery; compromise of these vessels is the most common cause of postoperative hypoparathyroidism.

APPROACH TO LYMPH NODE DISSECTION — The indications for central and lateral compartment lymph node dissection are reviewed below. The surgical approach, intraoperative challenges, and operative complications are reviewed separately. (See "Neck dissection for differentiated thyroid cancer".)

Nomenclature — A frequently used nomenclature defines level I nodes as submental and submandibular; level II, III, and IV nodes as upper, middle, and lower jugular, respectively; level V nodes as posterior; and level VI nodes as anterior central compartment (figure 3) [36].

Therapeutic neck dissection refers to lymph node dissection when nodal disease is identified or suspected based upon clinical examination or ultrasound evaluation, whereas prophylactic dissection refers to lymph node dissection when nodal disease is not identified preoperatively.

Our approach — In patients with differentiated thyroid cancer, we perform a preoperative assessment of nodal status with ultrasound. A neck dissection for differentiated thyroid cancer (papillary and follicular) should be performed as a therapeutic procedure when nodal disease is identified or suspected based upon the clinical examination or ultrasound evaluation.

A prophylactic central neck dissection (level VI) for patients with thyroid cancer is controversial. It is not necessary for small, noninvasive papillary and most follicular cancers. However, for patients with advanced primary tumors (>4 cm and/or with extrathyroidal invasion), clinically involved lateral lymph nodes, or if the information will contribute to the planning of further therapy, we perform prophylactic central lymph node dissection. (See 'Therapeutic lymph node dissection' below and 'Prophylactic lymph node dissection' below.)

Therapeutic lymph node dissection — Therapeutic lymph node dissection should be performed if there is clinical evidence (on exam or ultrasound) of central or lateral node metastases due to the increased risk of neck recurrence and mortality [27]. This approach is consistent with the National Comprehensive Cancer Network (NCCN) and American Thyroid Association (ATA) guidelines, which recommend central and/or lateral neck dissection only in the presence of grossly positive metastases [6,18].

During the operation, the lymph nodes should be inspected, and any suspected of containing cancer should be biopsied.

●If nodes in the central compartment (level VI, the region bounded by the jugular veins, the hyoid bone, and the upper mediastinum) are found to contain cancer, dissection of all lymphatic and surrounding tissue in that compartment should be performed (figure 4).

●If any nodes in the upper, middle, or lower jugular nodal groups (levels II, III, IV) are found to contain cancer, complete dissection of nodal tissue along the jugular and carotid vessels should be done. Radical dissection, with removal of the internal jugular vein, spinal accessory nerve, and sternocleidomastoid muscle, is rarely necessary.

There is general agreement that therapeutic node dissection should be performed in patients with papillary cancer who have visibly involved nodes [6,37]. We perform lateral node dissection based upon intraoperative gross involvement or preoperative ultrasound detection [38]. Preoperative cervical ultrasound can detect clinically nonpalpable, metastatic nodes in up to 20 percent of patients with papillary cancer, including those with primary tumors <1 cm in diameter [4,39]. Lateral compartment nodes containing metastases detectable by ultrasound are associated with a shortened relapse-free survival, whereas those only found by histologic examination do not predict altered outcomes [39].

Although cervical nodal metastases are rare in patients with follicular cancer, patients with the Hürthle cell variant may have nodal disease (which predicts a worse outcome) and should have a therapeutic neck dissection if metastatic lymph nodes are identified [38].

Prophylactic lymph node dissection — We agree with the ATA guidelines, which suggest prophylactic central compartment neck dissection (ipsilateral or bilateral) for advanced primary tumors (>4 cm and/or with extrathyroidal invasion), clinically involved lateral lymph nodes, or if the information will contribute to the planning of further therapy, but is not necessary for small, noninvasive papillary and most follicular cancers [6]. There are no data to show that routine prophylactic lateral neck dissection benefits patients' long-term survival [40,41], and therefore, we do not perform this procedure.

Microscopic regional lymph node metastases of papillary cancer occur in up to 80 percent of patients. However, only approximately 35 percent have cervical or mediastinal node metastases that are detected at the time of initial surgery. Because microscopic nodal disease is rarely of clinical importance or subsequent radioiodine administration ablates these occult foci, and observational studies have not shown a clear benefit in reducing locoregional recurrence rates, many authors argue that prophylactic neck dissection of microscopic lymph node metastases that are not clinically identifiable at the time of surgery may not improve long-term outcome and could subject patients to more risk than benefit [42-45].

However, the precise role of prophylactic neck dissection for well-differentiated thyroid cancer remains controversial because in experienced hands, this procedure can be done with minimal additional risk [46], and some observational studies have suggested a survival benefit in selected patients [47-50]. Since thyroid cancers harboring the BRAF mutation have the potential to be more clinically aggressive and less responsive to radioiodine adjuvant therapy, some authors have suggested that prophylactic central neck dissection be considered for these patients [51]. However, until additional data are available demonstrating a clinical benefit to this approach, we are not advocating prophylactic neck dissection on the basis of the molecular profile of the tumor at the current time.

Others who routinely perform prophylactic central neck dissection argue that the absence of involved nodes and adverse pathological features modifies the indication for radioiodine therapy in many patients. In a retrospective study of 115 patients with papillary thyroid cancers under 2 cm (without ultrasound evidence of cervical nodes) undergoing neck dissection, 13 of 115 patients were identified (11 percent) who were expected to receive adjunctive radioiodine therapy but did not because of the surgical findings [52]. Follow-up in this study was only one year, and any benefit of avoiding radioiodine therapy has to be balanced against the risk of complications of neck dissection.

SURGERY FOR INVASIVE DISEASE — The primary tumor or local and regional metastases may invade the strap muscles, trachea, recurrent laryngeal nerves (RLNs), larynx, esophagus, thoracic duct, or carotid sheath. Careful preoperative and intraoperative evaluation, including laryngoscopy and symptom-guided imaging studies, is essential [11].

Conservative procedures, such as vertical hemilaryngectomy for unilateral laryngeal cartilage invasion or circumferential tracheal resection for subglottic invasion, may allow maintenance of function [53]. However, extensive intraluminal invasion may occasionally necessitate total laryngectomy. While attempting to preserve normal organ function is important, gross resection of all visible tumor, if possible, should be the goal of surgical intervention.

COMPLICATIONS — Thyroid surgery is associated with risk for metabolic complications, of which hypoparathyroidism is the most common, and anatomic complications, including damage to the laryngeal nerves. Both complications are more likely to occur after total thyroidectomy combined with lymph node dissection [54]. (See "Thyroidectomy", section on 'Complications'.)

Postoperative hypoparathyroidism is rare following lobectomy because a unilateral procedure avoids the contralateral neck. Similarly, although hoarseness may result from damage to one recurrent laryngeal nerve (RLN) in approximately 1 percent of cases, a unilateral procedure avoids the possibility of bilateral paralysis [55].

Hypoparathyroidism — Hypoparathyroidism is the most frequent complication of total or near-total thyroidectomy. Transient hypoparathyroidism occurs in up to 20 percent of patients after surgery for thyroid cancer [56,57], and permanent hypoparathyroidism occurs in 0.8 to 3 percent of patients after total thyroidectomy [54,56,58-60] and is more common when anatomic landmarks are displaced and obscured.

The hallmark of acute hypocalcemia is tetany, which is characterized by neuromuscular irritability. The symptoms of tetany may be mild (peri-oral numbness, paresthesias of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures, which must be distinguished from the generalized tonic muscle contractions that occur in severe tetany). Chvostek's and Trousseau's signs are indicative of neuromuscular irritability due to hypocalcemia. (See "Clinical manifestations of hypocalcemia", section on 'Tetany'.)

Current requirements for short hospital stays argue for early treatment of hypocalcemia. We generally use the following regimen (table 1):

●Patients with symptomatic hypocalcemia (circumoral and distal extremity paresthesias) or a serum calcium concentration below 7.8 mg/dL (2 mmol/L, with correction for any abnormality in the serum albumin concentration) should be treated with calcitriol 0.5 mcg twice daily and calcium carbonate 500 mg four times daily. For patients who absorb calcium carbonate poorly, calcium citrate may be used. Calcium glubionate is available as a liquid, although calcium carbonate can be crushed and mixed with water to form a drinkable slurry.

●Patients with more severe symptoms (muscle cramps) or a serum calcium concentration below 7.5 mg/dL (1.9 mmol/L) should also receive calcium gluconate by continuous intravenous drip for 24 to 36 hours or until the serum calcium concentration rises and is maintained above 8 mg/dL (2 mmol/L). Details on preparing the intravenous calcium solution are found elsewhere. (See "Treatment of hypocalcemia", section on 'Intravenous calcium dosing'.)

●Emergency therapy is indicated in patients with tetany, seizures, laryngospasm, or markedly prolonged QT intervals on the electrocardiogram. Treatment is initiated with the intravenous administration of one 10 mL ampule of 10 percent calcium gluconate over 5 to 10 minutes, followed by calcium gluconate by continuous intravenous drip for 24 to 36 hours or until the serum calcium concentration rises and is maintained above 8 mg/dL (2 mmol/L). (See "Treatment of hypocalcemia", section on 'Intravenous calcium dosing'.)

●If oral vitamin D and calcium carbonate cannot be tapered and then discontinued over the next two to eight weeks, the hypoparathyroidism may be permanent. Measurement of serum parathyroid hormone (PTH) concentrations when serum calcium is low can confirm the permanent need for treatment. (See "Hypoparathyroidism", section on 'Management'.)

An alternative approach is to treat all patients undergoing thyroidectomy with calcitriol and calcium carbonate starting the day before surgery, in an effort to avoid the postoperative hypocalcemia, with a plan to taper and eventually discontinue these medications over the next few weeks.

Hypoparathyroidism is reviewed in more detail separately. (See "Hypoparathyroidism", section on 'Acute hypoparathyroidism: Postsurgical'.)

Recurrent and superior laryngeal nerve injury — Occasionally, the RLN must be sacrificed intentionally due to direct tumor invasion into the nerve or surrounding tissues. As a postoperative complication, unilateral paresis of the RLN has been reported in approximately 3.9 percent of patients and bilateral in 0.2 percent [61]. However, after six months, the incidence of nerve paresis was only 1 percent, suggesting that injury may be temporary.

Endotracheal intubation or laryngeal mask airway ventilation can cause RLN injury as well as arytenoid dislocation, vocal cord edema, and other causes of postoperative hoarseness. High division of the vagus nerve near the carotid bulb will paralyze both the superior laryngeal nerve (SLN) and the RLN, resulting in both sensory and motor deficits with significant risk for aspiration. Injury to the SLN results in voice weakness or fatigue as well as changes to both voice quality and pitch. Injury to the RLN may result in paresis or paralysis of the true vocal cord to a paramedian or lateral position.

Intraoperative monitoring of RLN function may reduce this complication, but data are conflicting. Intraoperative neuromonitoring and nerve injury following thyroidectomy are reviewed in more detail separately. (See "Thyroidectomy", section on 'Nerve injury/vocal cord paresis or paralysis'.)

POSTOPERATIVE THYROID HORMONE THERAPY — After thyroid surgery, patients require postoperative thyroid hormone therapy both to replace normal hormone production and to suppress regrowth of tumor. Thyroid hormone therapy, including goals for thyroid hormone suppression, is reviewed in detail separately. (See "Differentiated thyroid cancer: Overview of management", section on 'Postoperative thyroid hormone' and "Differentiated thyroid cancer: Overview of management", section on 'Thyroid hormone suppression'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Thyroid nodules and cancer".)

SUMMARY AND RECOMMENDATIONS

●We suggest preoperative ultrasound evaluation of the central and lateral neck lymph nodes for all patients with malignant cytological findings on the fine-needle aspiration (FNA) and additional imaging in patients with locally advanced disease. (See 'Importance of preoperative imaging' above.)

●The primary therapy for differentiated (papillary and follicular) thyroid cancer is surgery. Surgical options include total/near-total thyroidectomy or unilateral lobectomy with isthmusectomy. The operative approach depends upon the extent of the disease (eg, primary tumor size and the presence of extrathyroidal extension or lymph node metastases), the patient's age, and the presence of comorbid conditions. Subtotal thyroidectomy is an inadequate procedure for patients with thyroid cancer. (See 'Types of procedures' above.)

●For patients with papillary or follicular cancer with a primary tumor >4 cm in diameter, extrathyroidal extension of tumor, or metastases to lymph nodes or distant sites, we recommend total thyroidectomy (Grade 1B). (See 'Choice of procedure' above.)

●For patients with 1 to 4 cm intrathyroidal tumors, either thyroid lobectomy or total thyroidectomy can be performed depending on the preference of the patient and the treatment team. We usually reserve thyroid lobectomy for tumors less than 3 cm confined to the thyroid without evidence of aggressive histologies or vascular invasion. Total thyroidectomy is preferred for tumors greater than 3 cm or if there are ultrasonographic findings in the contralateral lobe or in cervical lymph nodes that would make follow-up difficult. (See 'Choice of procedure' above.)

However, it is recognized that if an experienced thyroid surgeon is unavailable and the patient cannot be referred elsewhere, a near-total thyroidectomy or a lobectomy may be preferable to a more complete operation complicated by bilateral nerve damage.

●For patients with intrathyroidal unilateral differentiated thyroid cancer <1 cm, we suggest a thyroid lobectomy and isthmusectomy rather than total thyroidectomy (Grade 2B). The 30-year survival rate for this subgroup of patients approaches 100 percent. If there are clear indications to remove the contralateral lobe (eg, microcalcifications or small [3 to 4 mm] nodules with suspicious characteristics in the contralateral lobe, previous history of head and neck radiation, strong family history of thyroid cancer, or imaging abnormalities that will make follow-up difficult), total thyroidectomy is preferred. (See 'Choice of procedure' above.)

●For patients with thyroid cancer with clinical evidence (on exam or ultrasound) of central or lateral node metastases, we recommend therapeutic regional lymph node dissection (Grade 1B). For patients with large primary tumors (>4 cm), high-risk features for recurrence (extrathyroidal invasion), or if the information will contribute to the planning of further therapy, we suggest prophylactic central compartment lymph node dissection (Grade 2C). Prophylactic central lymph node dissection is not necessary for small, noninvasive papillary and most follicular cancers. (See 'Approach to lymph node dissection' above.)

●Because of the high risk of hypocalcemia after thyroidectomy, serum calcium concentration should be measured the evening and first morning after thyroidectomy. Treatment of postoperative hypocalcemia should be tailored to the severity and expected duration of parathyroid deficiency (table 1). (See 'Hypoparathyroidism' above.)