Initial Management

Management Recommendations

1. Preoperative Assessment

A. Patient History & Physical Exam Impacting Operative Risk^​1​

AAES

In anticipation of thyroid surgery, the following history and physical exam findings should be elicited and identified:

• Personal or family history of complications associated with general anesthesia.
• Personal history of general anesthesia challenges due to difficult intubation or limited oral opening.
• Presence of a neck scar or prior neck surgery that includes:
  • Carotid procedure,
  • Cervical spine surgery, 
  • Thyroid or Parathyroid procedure
• Any history of either a bleeding or clotting abnormality.
• Medication that affects clotting including antithrombotic or antiplatelet drugs.
• Any preexisting condition that causes chronic diarrhea such as irritable bowel disease (IBD) or Roux en Y gastric bypass.
• Patients who have undergone gastric bypass surgery and are scheduled to undergo either a total thyroidectomy or a completion thyroidectomy, should be advised that they are at increased risk of severe postoperative hypocalcemia.

B. Hypercalcemia^​2​

AAES

• Patients who are diagnosed with hypercalcemia and are scheduled to undergo thyroid surgery should undergo evaluation for hyperparathyroidism 
• Concurrent parathyroidectomy should be performed in patients who are undergoing thyroidectomy and are diagnosed with primary hyperparathyroidism 
• Patients with familial primary hyperparathyroidism who are scheduled for thyroid surgery should undergo preoperative evaluation for coexisting hyperparathyroidism 

C. Imaging for Biopsy Proven or Suspicious Thyroid Nodules

ATA // AAES // NCCN // TIRADS

• Ultrasound of the thyroid and neck including lateral lymph node compartments is recommended for all patients undergoing thyroidectomy for malignant or suspicious nodules. Meticulous documentation of the size, location, and invasion of adjacent structures is important.^{​1,3–5​}
• Cross-sectional imaging (CT, MRI) with intravenous contrast is recommended for patients with advanced disease, including invasive or symptomatic primary tumors, or clinically apparent multiple or bulky lymph node involvement.^​1,4​
• Fine-needle aspiration of sonographically suspicious lymph nodes is recommended to confirm malignancy if technically feasible and if this would change management.^​2,3,6​
  • For patients to be classified as cN1b, only one positive node needs to be documented in the lateral neck.

• A suspicious node in the central compartment should be biopsied if technically feasible and if this would change management. An alternative approach is to excise any suspicious central compartment nodes at the time of surgery and obtain frozen section analysis.
• Thyroglobulin washout from suspicious lymph nodes is appropriate in selected patients in addition to cytology, though interpretation may be difficult in patients with an intact thyroid gland.^​6​
• FDG-PET is not recommended in routine imaging for first-line evaluation of most thyroid cancers.^​5,6​

2. Active Surveillance (AS)

A. Intrathyroidal Papillary Thyroid Cancer ≤ 1 cm

ATA // ESMO // JAES // NCCN

• In properly selected patients with low-risk papillary thyroid cancer ≤ 1 cm in maximal dimension (T1a, papillary microcarcinomas) that appears to be confined to the thyroid, an active surveillance (AS) management approach can be considered as an alternative to thyroid surgery. Primary tumors that are located on the posterior surface of the thyroid lobe in proximity to the recurrent laryngeal nerve are not considered ideal candidates for AS.
• Clinical features that would favor surgical intervention rather than active surveillance include:
  1. Cytology indicating aggressive variant,
  2. Location of the tumor in a subcapsular location near the recurrent laryngeal nerve or trachea,
  3. Evidence of metastatic disease,
  4. Radiation exposure, or extrathyroidal extension,
  5. Age < 20 years,
  6. Other surgical disorders of the thyroid or parathyroid in patients with suitable low risk cancers.
• The presence of tumors located on the anterior surface of the thyroid and showing imaging evidence of minimal invasion of the overlying strap muscles represent an area of some controversy in terms of suitability for AS. However, certain guidelines do endorse the safety of AS in this group of patients.
• There is no reliable information to support the safety of AS based on the presence of specific mutations.
• Patients with low-risk thyroid cancers that are deemed to be suitable candidates for AS do not need a chest CT prior to AS but may require one if the disease progresses.
• Multifocal disease, if all lesions meet low risk criteria, is not a contraindication for AS.
• Patients with a family history of thyroid cancer may be suitable candidates for AS.
• Patients with otherwise favorable micropapillary thyroid cancers should not be excluded from AS on the basis of the degree of vascularity of the nodule or the pattern or degree of calcification.
• Patients with coexisting Graves’ Disease and a suitable micropapillary thyroid cancers for monitoring should not be excluded from AS.
• There may be a role for TSH suppression in patients undergoing AS.

B. Frequency & Duration of Ultrasound Studies

ATA // JAES // NCCN

• Active surveillance includes ultrasound evaluations every 6 months for 2 years, followed by annual surveillance.^​5–7​
• It is advisable to continue AS throughout a patient’s life including into more advanced years due to concern for the potential for more aggressive disease to appear in older patients.^​7​

C. Indications to Advise Surgery for Patients

ATA // JAES

1. Tumor diameter of:

2. Tumor Growth:
   • Increase in the maximal diameter of the nodule by > 3 mm.
   • Growth defined as a 20% increase in at least two nodule dimensions and a minimal increase of 2 mm, or a 50% or greater increase in volume.^​3​
3. Appearance of new lymph nodes.
4. Appearance of other thyroid or parathyroid disease.
5. Change in patient preference.

3. Surgical Treatment

A. Extent of Initial Thyroid Surgery

ATA // ESMO // JAES // NCCN

The appropriate extent of thyroid resection; namely, ipsilateral lobectomy (LT) versus total thyroidectomy (TT) is controversial for low-risk PTC and FTC. Decisions about the extent of thyroidectomy should be individualized and determined in consultation with the patient. Consideration should be given to the fact that TT enables radioactive iodine therapy, enhances post-treatment assessment with serum thyroglobulin and generally has a lower rate of recurrence; however, there is a higher rate of surgical complications including hypoparathyroidism and recurrent laryngeal nerve injury, especially among low-volume surgeons.^​5–8​

Preoperative risk assessment and risk-adapted decision-making for extent of thyroidectomy are crucial. In general, TT is recommended for ATA high-risk cases and LT for ATA low-risk cases. 

ATA Low-risk, well-differentiated cancers should meet all the following criteria: 

• Primary tumor < 4 cm, no ETE, cN0, cM0.^​5–8​
• The nodal criteria for low-risk thyroid cancers include nodes that are not clinically evident and less than 5 pathologic nodes where all nodes are micrometastases (< 2 mm).^​5,6​
• Unilateral nodules in the thyroid or low-risk appearing nodules in the contralateral lobe,^​5,6,8​
• No prior head and neck radiation exposure,^​5,6,8​
• No family history of thyroid cancer,^​5,6,8​ and
• No aggressive features on cytology.^​5,6,8​

For patients with ATA intermediate-risk tumors (not belonging to the low-risk or high-risk group), either TT or LT can be chosen. Some of the following features may only be known after surgical excision and histologic review.

• ATA Intermediate risk cancers include one or more of the following criteria:^​5,6​
  • Minimal extrathyroidal extension.
  • Presence of aggressive histologic features including hobnail, tall cell and columnar.
  • Evidence of vascular invasion in PTC.
  • Clinically evident nodal disease.
  • > 5 pathologic lymph nodes all < 3 cm in greatest dimension.
  • Multifocal micropapillary thyroid carcinomas with ETE and BRAF^v600E mutation.
  • Evidence of nodal disease on the first post treatment whole body scan.

B. Indications for Thyroid Lobectomy^​5,7​

JAES // NCCN

• Unilateral nodules in the thyroid, with or without low-risk appearing nodules in the contralateral lobe (for nodules in the contralateral lobe that meet criteria for FNA, FNA is recommended prior to surgery)
• No family history of thyroid cancer 
• No aggressive cytologic features
• Follicular neoplasms (Bethesda IV) that lack evidence of invasion or metastatic disease

C. Presence of Contralateral Nodules

For nodules in the contralateral lobe that meet criteria for FNA, FNA is recommended prior to surgical intervention.

D. Indications for Total Thyroidectomy

ATA // ESMO // JAES // NCCN

Total thyroidectomy is advisable for patients with tumors displaying ATA high-risk features that include the following:

• Maximal diameter of tumor T > 4 cm.
• Gross extrathyroidal extension (ETE).
• Clinically apparent lymph node metastasis (cN1).
  • Certain guidelines limit the high-risk criteria to N1 > 3 cm or N1 with extranodal extension.
• Clinically apparent distant metastasis (cM1).
• Poorly differentiated or aggressive features on cytology.
• Patients with prior head and neck radiation exposure in childhood or adolescence are candidates for TT.

There is a controversy concerning minimal ETE or ETE only to the sternothyroid muscle (T3b).

• Certain guidelines recommend TT for patients with minimal ETE or T3b tumor;^​8​
• Other guidelines do not include T3b tumor in the high-risk group and consider LT to be an appropriate surgical procedure.^​7​

E. Indications for Intraoperative Frozen Section

ATA // AAES

• Frozen section can provide important information regarding the presence of central compartment lymph node metastases in situations where that information will change the surgical procedure.^​2​
• Frozen section may be useful in confirming malignancy where that information will change the surgical procedure; frozen section is most likely to be informative for classic PTC and unlikely to be definitive for either follicular carcinoma or follicular variant of PTC.^​6​
• Frozen section may play a role in confirming the identification of parathyroid tissue.^​2​

4. Completion Thyroid Surgery

A. Indications Following Thyroid Lobectomy

ATA // AAES // ESMO // NCCN

• In patients who undergo a lobectomy for either presumed benign or known malignant disease, the final pathology will inform the treatment team as to the biologic aggressiveness of the disease. The decision to perform a completion thyroidectomy should be made when a total thyroidectomy would have been initially advisable if the histologic information was known either preoperatively or intraoperatively.^​2,6​
• Indications for completion thyroidectomy either based on intraoperative findings or after surgery include:
  • Tumor > 4 cm.^​2,5,6​
  • Identification of distant metastases.^​5–8​
  • Gross positive resection margins.^​5​
  • Gross extrathyroidal extension including RLN or tracheal involvement.^​2,5,6​
  • Macroscopic multifocal disease (> 1 cm).^​5​
  • Confirmed nodal metastases except where the nodal disease is incidental (N1A) and there are fewer than 5 pathologically confirmed nodes and none of the nodes is > 5 mm or all nodes are < 2 mm size. ^​6​
  • Poorly differentiated thyroid cancer.^​5​
  • Confirmed contralateral malignant disease.^​5​
• ATA Intermediate-risk features not included above for which the surgeon should consider a completion thyroidectomy following a thorough discussion with the patient and a multidisciplinary care team:
  • Aggressive histology (e.g., tall cell, hobnail variant, columnar cell carcinoma).^​6​
  • Papillary thyroid cancer with vascular invasion.^​5​
  • Clinical N1 or > 5 pathologic N1 with all involved lymph nodes < 3 cm in largest dimension.^​7​
  • Multifocal papillary microcarcinoma with ETE.^​6​

i. Indications for Follicular Carcinoma

ATA // JAES // NCCN

• Minimally invasive follicular carcinoma does not require completion thyroidectomy.^​6​
• Vascular invasion (> 4 vessels) should undergo a total thyroidectomy.^​5–7​
• High risk features for which completion thyroidectomy should be considered include:
  • Age > 45 years and size > 4 cm.^​7​

B. Preoperative Evaluation Before Completion Thyroidectomy

AAES // NCCN

• All patients being considered for a completion thyroidectomy should undergo an examination of their larynx to confirm mobility of the vocal cord on the initial side of surgery.^​2​
• Prior to embarking on a completion thyroidectomy, a thorough assessment of the lateral compartments should be performed to determine if there are clinically evident lateral compartment nodes if that assessment had not been performed prior to the initial lobectomy. Biopsy of suspicious central and lateral compartment nodes should be performed.^​5​
• In the patient deemed to be a candidate for a completion thyroidectomy based on initial or final pathology and who experiences an injury to the RLN at the time of the initial surgery, the surgeon may elect to:
  • Wait for a reasonable period of time for the vocal cord to recover function.
  • Proceed with surgery on the contralateral side following extensive discussions with the patient.^​2​

5. Extent of Lymph Node Surgery

ATA // AAES // ESMO // JAES // NCCN

6. Perioperative Voice Assessment & Laryngeal Exam

ATA // AAES // NCCN

• Preoperative assessment of a patient’s voice should be undertaken by the treating surgeon as part of the physical exam. Documentation should be performed of both the patient’s and physician’s assessment of voice as well as any recent changes.
• An assessment of the larynx by any of a number of modalities should be carried out (ultrasound, mirror indirect or fiberoptic laryngoscopy) in all patients who meet the following criteria:^​1,5,6​
  • Preoperative voice changes or complaints.
  • Prior surgery involving the neck or mediastinum that is in proximity to the recurrent laryngeal or vagal nerves.
  • Evidence or suspicion of locally invasive cancer.
  • The presence of extensive central compartment nodal disease.
• Postoperative voice assessment should be performed in all cases, including a formal laryngeal examination of those patients who are identified as having a persistent postoperative voice abnormality.^​1​

A. Neuromonitoring^​1​

While performing thyroid surgery, the surgeon should make every effort to preserve the recurrent and the superior laryngeal nerves. Direct visual identification of the RLN and its branches is imperative in all cases.

B. Parathyroid Gland Management During Surgery^​1​

While performing thyroid surgery, the parathyroid glands and their vascular supply should be preserved. Dissection should be performed along the thyroid capsule to help preserve the parathyroid glands. The vitality of the mobilized glands should be assessed at the completion of the procedure and consideration should be given to parathyroid autotransplantation of any parathyroid where viability is uncertain.

7. Initial Evaluation of Invasive Thyroid Cancer

AAES // AHNS

• Invasive thyroid cancer that affects the upper aerodigestive tract (UADT) structures including the larynx, trachea and esophagus, should be removed when technically feasible based on histology, disease extent, age, comorbid conditions, the presence of distant metastases (M1), and patient motivation.^​2​
• The extent of surgical resection is best guided by the degree of UADT invasion with a range of techniques employed to remove all gross disease and preserve or restore function.^​2​
• Preoperative histologic assessment is very important to surgical decision making and open incisional biopsy may be necessary in patients with suspicion of anaplastic thyroid cancer or primary thyroid lymphoma.^​1​
• Preoperative examination of the larynx is advisable in the management of invasive thyroid cancer and the preferred method is fiberoptic laryngoscopy.^​2​
• Aggressive thyroid disease should ideally be managed in a multidisciplinary setting.^​2​

A. RLN Management^​2​

AHNS // JAES

• Management of the RLN in patients with invasive thyroid cancer (TC) should be based on the following guidelines:^​7​
  • Resection of the encased RLN should be performed if ipsilateral paresis or paralysis is identified on preoperative examination.
• Encasement or minimal adherence of the RLN in the presence of bilateral normal vocal cord mobility should be managed by shaving of the tumor off the RLN provided that all gross disease is removed.^​7​
• If the RLN is encased by tumor and the contralateral vocal cord shows impaired mobility on preop exam, then the encased RLN should be spared by shaving disease off that RLN in an effort to avoid a tracheostomy.

Following sparing of an encased RLN, adjuvant therapy should be considered.

• Confirmation of the histology of the tumor involving an RLN is essential prior to nerve sacrifice which should be avoided in the setting of lymphoma and benign disease.
• If the circumstances permit, based on the proximity to the cricothyroid joint of the point of sacrifice of an involved RLN, a reinnervation procedure should be performed in the primary setting.^​7​
• Intraoperative neuromonitoring may play a very important role in the management of invasive thyroid cancer by providing important information regarding the functional status of the RLN both during and at the completion of the procedure.
• Intraoperative neuromonitoring should be strongly considered in the management of invasive thyroid cancer especially when preoperative vocal cord dysfunction is identified.
• Neuromonitoring may be helpful with intraoperative decisions regarding:
  • The decision to proceed to the contralateral side of the thyroid.
  • The decision to sacrifice an encased RLN.
  • The need for a tracheostomy.

B. Tracheal Invasion

ATA // AHNS // JAES

• Tracheal resection should be performed when thyroid cancer is identified as invading the tracheal wall.
• A variety of factors should be accounted for including:^​7​
  • Disease stage.
  • Degree of disease spread.
  • Risk of surgical complications.
  • Overall prognosis.
  • Impact on quality of life.
  • Patient or caregivers’ wishes.
  • Skill of the surgical team.
• If there is suspicion of laryngotracheal invasion based on physical exam, patient symptoms or documented presence of distant disease, then cross sectional imaging (CT, MRI) should be performed to provide more detailed information than can be obtained by US examination.^​2,6​
• In the setting of a high suspicion of laryngotracheal invasion, the surgical team should perform a bronchoscopy prior to or at the time of the ablative procedure. The surgical team should be prepared to perform a laryngotracheal resection and reconstruction at the time of the initial surgical procedure.^​2​
• Surgical management of the laryngotracheal complex is guided by the following basic tenets:^​2​
  • If a short segment of the laryngotrachea is found to have minimal cartilage invasion, then a shave excision is justified.
  • If preoperative or intraoperative determination of intraluminal invasion is identified then a sleeve resection and primary repair should be performed (based on imaging, preoperative endoscopy, or surgical findings).
  • If the surgeon performing the thyroidectomy does not have the skills or the experience to perform laryngotracheal ablative and reconstructive surgery then a head and neck or thoracic surgeon with expertise should be available. If neither of these conditions can be met then the surgeon performing the thyroidectomy should close the surgical wound and consider referral to a tertiary center where these skill sets are available.

C. Laryngeal Invasion

AHNS

• The following are basic tenets of laryngeal management when involved by invasive thyroid cancer:
  • Shave excision of gross disease involving a partial thickness of the laryngeal framework should be performed when feasible.^​2​
  • Partial or total laryngectomy should be performed in cases with gross invasion of the larynx and involvement of the endolarynx.^​2​
• If the surgeon performing the thyroidectomy is not experienced or skilled in partial or total laryngectomy, that expertise should be sought locally or referral to a medical center where that expertise is available.^​2​

D. Esophageal Invasion^​2​

AHNS

Management of the esophagus when involved by invasive thyroid cancer should adhere to the following basic tenets:

• Resection of the esophageal muscularis can be performed without creating a through and through defect when intraluminal invasion is not present.
• A through and through resection of the esophageal wall should be performed when transmural invasion is present.
• Reconstruction of a full thickness defect of the esophagus should be performed by primary repair for smaller defects or with regional or free tissue transfer in the case of larger defects.

E. Vascular Invasion: Workup & Management^​2​

AHNS

• When vascular invasion is suspected or identified by imaging then appropriate workup with imaging is required to determine whether the tumor is resectable. 
• CT angiogram and/or MR angiogram should be used to provide information regarding the safety of vascular control and resectability.
• Preoperative assessment to the adequacy of collateral intracranial blood flow and the detailed anatomy of the Circle of Willis should be determined and balloon test occlusion should be considered in order to determine whether carotid shunting is needed during carotid resection and reconstruction.
• One internal jugular vein can be safely resected and flow not restored if the contralateral jugular vein is patent.
• In the event that both jugular veins must be resected, a staged procedure should be performed or reconstitution of flow in at least one vein should be established.
• Partial resection of the vessel wall can be performed for focal invasion and vascular reconstruction with a patch performed when amenable.

8. Key Elements of Communication^​6​

ATA

A summary of the key elements that will likely have a major impact on the peri-operative risk assessment of patients with WDTC and should be communicated clearly to all members of the multidisciplinary team. Many of these elements may influence decision-making in regard to the role of future surgery, the need for and planning of radioactive iodine and other treatment modalities.

A. Preoperative Evaluation for Well-differentiated Thyroid Cancer^​5–8​

ATA // ESMO // JAES // NCCN

• A careful history and physical examination that includes a previous history of head and neck radiation and clinical features of local invasiveness including vocal cord function.
• An anatomical assessment of the primary tumor with ultrasound and/or cross-sectional imaging, looking for features of invasiveness, extent of local and regional disease, and lymph node mapping of the regional basin.

B. Intra-operative Evaluation & Prognostic Indicators^​6​

ATA // ESMO // JAES // NCCN

Convey the following to the multidisciplinary team.

• The presence of gross tumor invasion into the surrounding muscles, trachea, esophagus or soft tissue.
• The extent of the surgical resection either R0, R1 and a detailed description of the gross residual disease left behind.
• Documentation of any normal residual thyroid tissue left to protect the recurrent laryngeal nerve and/or parathyroid glands.
• The extent and the compartments of any lymph node dissection.
• The status of the recurrent laryngeal nerve(s).
• The viability and status of the parathyroid glands.
• The utilization of a standardized narrative or synoptic operative report is recommended to ensure all these elements are clearly documented and articulated.
• Although implied but not clearly articulated, gross residual disease is an important element for the stratification of postoperative treatment modalities.^​5–8​

C. Post-operative Risk Stratification & Ongoing Management

ATA // ESMO // NCCN

• An optimized standardized pathology report required for AJCC/UICC thyroid cancer staging.^​5,6,8​
• Postoperative complications including hypoparathyroidism, RLN function, chyle leak, Horner’s syndrome. These complications should be documented and communicated due to their importance in influencing further treatment and recommendations for completion thyroidectomy, re-operative surgery and timing of any adjunct therapies.^​5–7​
• Postoperative ultrasound documenting thyroid bed remnant, the presence of any residual disease as well as a detailed lymph node mapping should be standardized.^​8​
• The addition of a neck ultrasound should be utilized on postoperative patients to aid with risk-stratification.^​5,6,8​

References

1. 1.

   Patel K, Yip L, Lubitz C, et al. Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg. 2020;271(3):399-410. doi:10.1097/SLA.0000000000003735
2. 2.

   Shindo ML, Caruana SM, Kandil E, et al. Management of invasive well-differentiated thyroid cancer: An American head and neck society consensus statement: AHNS consensus statement. Head Neck. Published online August 2014:n/a-n/a. doi:10.1002/hed.23619
3. 3.

   Tessler FN, Middleton WD, Grant EG, et al. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. Journal of the American College of Radiology. Published online May 2017:587-595. doi:10.1016/j.jacr.2017.01.046
4. 4.

   Carty S, Doherty G, Inabnet W, et al. American Thyroid Association statement on the essential elements of interdisciplinary communication of perioperative information for patients undergoing thyroid cancer surgery. Thyroid. 2012;22(4):395-399. doi:10.1089/thy.2011.0423
5. 5.

   Haddad RI, Nasr C, Bischoff L, et al. NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018. J Natl Compr Canc Netw. Published online December 2018:1429-1440. doi:10.6004/jnccn.2018.0089
6. 6.

   Haugen B, Alexander E, Bible K, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020
7. 7.

   Ito Y, Onoda N, Okamoto T. The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: Core questions and recommendations for treatments of thyroid cancer. Endocr J. Published online 2020:669-717. doi:10.1507/endocrj.ej20-0025
8. 8.

   Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019;30(12):1856-1883. doi:10.1093/annonc/mdz400