Recurrent laryngeal nerve

The already challenging anatomy of the head and neck is further complicated by prior surgical interventions and adjuvant therapies, such as radiotherapy. The meticulous, skilled cervical endocrine surgeon may find that the usual landmarks and relationships found in the naïve thyroid bed are obscured or missing. However, this important knowledge and adherence to the dictum of recurrent laryngeal nerve (RLN) surgical visualization still serve to reduce inadvertent nerve injury.

In the operated thyroid bed, the RLNs may be hidden or encased in scar tissue, and the course of the nerve may be altered by the prior surgical maneuvers or by scar retraction. The RLNs originate from the vagus nerve in the inferior neck (right) or at the level of the aorta (left), return into the neck, and run behind the carotid sheaths as they proceed superiorly. Typically, the nerves may be located inferiorly, in a triangle bound by the carotid sheath contents laterally and by the trachea and esophagus medially. The nerves may lie a variable distance lateral to the tracheoesophageal groove on either side, a relationship altered further in the reoperative field. Both nerves transverse the course of the inferior thyroid artery, but multiple variations of this relationship have been described. The nerve travels superiorly, to enter the larynx at the posterior cricothyroid muscle and cricothyroid notch region. In this area, it can be intimately associated with the posterior suspensory ligament (Berry ligament), and even appear to involve the gland parenchyma itself. In 39% of cases, the nerve has been found to bifurcate before entering the larynx . The nerve may undergo even further branching, and at variable locations (0.6 to 3.5 cm from the cricoid cartilage). If this division is not recognized, one or more of the branches may be injured, emphasizing the need to identify the main trunk proximal to this potential division point. The nerve is most vulnerable to injury near the inferior thyroid artery, near the Berry ligament, and at the inferior pole of the gland .

The Zuckerkandl’s tubercle has been described as a useful landmark for localization of the RLN . This structure has been attributed to the Viennese anatomist, Zuckerkandl , from a 1902 publication describing a posterior projection of the thyroid, which he named the “tuberculum” or “processus posterior glandulae of thyroideae.” This tubercle is felt to represent the embryologic fusion of the ultimobranchial body and the principal median thyroid process. This structure can be identified in 63% to 80% of patients, and may be sizable (>1 cm) in 45% . The RLN is located medial to the tubercle in 93% of cases, and lateral in 7%. The superior parathyroid is typically superior to this structure. Although not helpful in the case of prior thyroid lobe resections, the Zuckerkandl’s tubercle may be used to help define the area of the RLN in parathyroid re-explorations, or in cases of partial thyroidectomy where exploration of the contralateral side but no resection of gland is performed.

Debate continues as to whether the RLN should always be identified during primary thyroid and parathyroid surgery. Some experienced surgeons report low RLN injury rates without specifically identifying the nerve intraoperatively . Clearly, in the age of minimally invasive surgery, this policy of nerve visualization with every surgery has been challenged. However, in the circumstance of revision surgery, the policy of nonvisualization of the RLN carries a higher risk for injury. Therefore, techniques to recognize and preserve the RLN should be used, including identifying the nerve caudally outside the prior operative field and tracing its course cranially; meticulous dissection along the course of the nerve; or use of nerve monitoring.

The rate of reported RLN injury varies in the literature. Reeve and colleagues report a 1.5% incidence of RLN palsy in repeat thyroid procedures, whereas Martensson and Terins report 14% permanent palsy. Repeated surgeries understandably seem to increase the risk. Beahrs and Vandertoll found that 8% of those undergoing a second surgery, and 22% undergoing a third, for benign disease suffered a permanent RLN palsy. When it was for malignant disease, the rate rose to 12% and 36%, respectively. These rates are well above the 1% typically quoted for a permanent RLN injury .

Superior laryngeal nerve

The superior laryngeal nerve (SLN) innervates only one muscle, but this muscle, the cricothyroideus, is important in vocalization, particularly in vocal projection and vocal endurance. Professional voice users, both speakers and singers, may have devastating changes in their professional careers from injury to the SLN. The average vocal user may also experience morbidity when trying to raise his or her voice. This nerve is not typically exposed, isolated, and dissected during thyroid bed procedures, as is the RLN. Although the nerve may be identified during surgery in 10% to 46% of cases, preservation of this nerve is typically improved if vascular dissection and ligation involves the individual vessels as they enter the gland, versus an en masse ligation . This concept is no different in revision surgery, but the nerve is at elevated risk secondary to the same scarring and contracture affecting the SLN.

Parathyroid

The parathyroid glands are more variable in their location than other endocrine glands. These glands typically exist as two pairs, but may number from two to nine. Primary exploration for parathyroid disease can be complicated by this variability (ie, inability to locate four glands, missed adenomas causing persistent hypercalcemia). Autopsy studies report that 84% of persons have four glands, 13% have more than four, and 3% have fewer than four . Of these glands, 1.3% are intrathyroidal . The addition of scarring from prior surgery obscuring these small organs and possible gland resection (deliberate or inadvertent) reduces the chances of successful identification. The inadvertent parathyroidectomy rate during total thyroidectomy has been reported to be from 5% to 15% .

The parathyroid glands may reside anywhere from the hyoid to the mediastinum. The inferior parathyroid glands are more variable than the superior glands, but are usually located caudal to the inferior thyroid artery and RLN crossing. Almost 50% of inferior glands are located in and around the inferior thyroid pole, but 25% may reside closer to thymus remnants, and only 2% are in the mediastinum . The superior glands are more likely to be within the thyroid capsule than the inferior glands but are also generally more consistent in their location superior to the RLN entrance to the larynx. Glands may be behind the esophagus, within the carotid sheath, or even on the anterior surface of the thyroid, approximating the strap muscles. Re-exploration for persistent hypercalcemia without clear preoperative imaging/localization mandates that these “usual suspect” locations be investigated.

Other structures

The carotid sheath and esophagus may also be altered in appearance and location and may be more vulnerable to inadvertent injury. With this distortion, care must always be taken during the surgery to confirm that structures dissected are identified and preserved. Other articles in this issue contain detailed discussions of these anatomic issues.

Ultrasonography

Ultrasonography has been one of the workhorse imaging modalities for thyroid and parathyroid disease. Because ultrasonography does not involve ionizing radiation, is comfortable for the patient, and does not affect the glandular tissue itself as some studies may (ie, iodinated contrast for CT), it is well accepted and may be repeated without real, demonstrable risk. High-resolution ultrasonography equipment may identify parathyroid glands in typical or atypical locations, demonstrate changes in the central neck worrisome for thyroid cancer recurrence, and distinguish changes in echogenicity, calcifications, or lymph node necrosis that may direct surgical efforts .

Ultrasonography has been compared with functional testing (sestamibi scan) and has been found to have similar sensitivity for parathyroid adenoma . Ultrasonography sensitivity was reported at 70%, compared with 63% for sestamibi, with positive predictive values of 90.2% and 90.5%, and negative predictive values of 24.7% and 22.5%, respectively. Ultrasonography was able to identify parathyroid adenoma in those who had nonlocalizing or incorrectly localizing sestamibi scans. Additionally, ultrasonography provides information about concomitant thyroid pathology, described in 20% to 60% of bilateral neck explorations for parathyroid disease. In multigland disease, some studies have suggested that ultrasonography and sestamibi, even when combined, are poor localizing studies, unless combined with intraoperative parathyroid hormone (PTH) testing .

CT and MRI

CT and MRI may provide the surgeon with anatomic images with which they tend to be more familiar than ultrasonographic images. These imaging modalities have typically been secondary to ultrasonography and the functional studies discussed later. However, they may play a role in combination with other studies.

Some researchers have shown that MRI has similar sensitivity in detecting parathyroid tissue when compared with dual-phase technetium-99m sestamibi , whereas others have determined it is inferior to technetium-99m sestamibi/iodine-123 subtraction scintigraphy. CT scan has no specific application for parathyroid disease, but can be used in thyroid disease, specifically if the thyroid tissue still takes up iodinated contrast. This modality with contrast, however, can delay the future application of radioactive iodine therapy in those who have iodine-avid, well-differentiated thyroid cancer. Therefore, its application in isolation is limited.

Sestamibi

Radionuclide scintigraphy may be used for reoperative imaging of parathyroid disease, either adenoma or hyperplasia . Dual-phase technetium-99m sestamibi is based on the preferential retention of the radionuclide in the mitochondria of abnormal parathyroid tissue. Other agents, such as technetium-99 tetrafosmin, are also used. Imaging parameters may be altered to create uniplanar or multiplanar images, or even three-dimensional ones (sestamibi single-photon emission computed tomography [SPECT]). Subtraction imaging techniques to enhance parathyroid visualization may be used to reduce thyroid shadowing. Agents include thallium, technetium-99 pertechnetate, and iodine-123. Extensive literature exists supporting the use of sestamibi technology in parathyroid localization. Given the functional nature of the imaging, tissue may be located regardless of the surrounding anatomic concerns, although a differential in uptake between the parathyroid tissue and surrounding tissue is necessary.

Radioactive iodine

Radioactive iodine has long been used for diagnostic and therapeutic measures in thyroid carcinoma. This functional examination may detect thyroid tissue that is uptaking iodine for thyroglobulin production. Therefore, a few criteria must be met for imaging to be successful: the gland must be well-differentiated thyroid tissue that is still active in iodinization, and the tissue must not be iodine saturated (ie, currently uptaking iodine). If any of these criteria is not met, radioactive iodine imaging may fail to detect the thyroid tissue.

Hybrid studies

At this juncture, many surgeons are turning to hybrid imaging studies that use the anatomic resolution of CT and the tissue-functional detection of sestamibi and fluoro-2-deoxy-D-glucose (FDG). SPECT/CT and positron emission tomography (PET)/CT have emerged as helpful diagnostic tools in parathyroid and thyroid disease.

SPECT/CT uses merged images from a gamma camera and CT to create a study in which the functional parathyroid tissue can be well localized anatomically. The relationship of the parathyroid tissue with surrounding structures identified on the CT scan provides the surgeon with the information necessary to plan a curative surgery, which is particularly useful in the ectopic gland or revision situation, where typical landmarks are no longer useful or possibly not even present. Several studies have shown the usefulness and, in certain circumstances, superiority of SPECT/CT in localizing the offending gland .

PET/CT scans have begun to be used in recurrent thyroid carcinoma. This technique’s role continues to evolve, but a body of literature supports its use, particularly in certain circumstances. The prime example is a previously treated patient who has well-differentiated thyroid carcinoma and is experiencing increasing thyroglobulin levels but has a negative I-131 uptake scan. FDG-PET has been shown to detect non–iodine-avid thyroid carcinoma, with a diagnostic accuracy higher than those of other modalities . The addition of CT scan to the FDG-PET can alter patient management by better directing the surgeon to the exact foci of disease in as high as 48% to 67% of cases . Metastasis was detected in 95% of cases of well-differentiated thyroid cancer . This modality seems to be most effective if the thyroglobulin level reaches more than 10 ng/mL . The more precise localization that can be done preoperatively, the more focused the surgery can be, thus potentially limiting unnecessary dissection and risk to the cervical structures.

Ultrasonography

Ultrasonography has been one of the workhorse imaging modalities for thyroid and parathyroid disease. Because ultrasonography does not involve ionizing radiation, is comfortable for the patient, and does not affect the glandular tissue itself as some studies may (ie, iodinated contrast for CT), it is well accepted and may be repeated without real, demonstrable risk. High-resolution ultrasonography equipment may identify parathyroid glands in typical or atypical locations, demonstrate changes in the central neck worrisome for thyroid cancer recurrence, and distinguish changes in echogenicity, calcifications, or lymph node necrosis that may direct surgical efforts .

Ultrasonography has been compared with functional testing (sestamibi scan) and has been found to have similar sensitivity for parathyroid adenoma . Ultrasonography sensitivity was reported at 70%, compared with 63% for sestamibi, with positive predictive values of 90.2% and 90.5%, and negative predictive values of 24.7% and 22.5%, respectively. Ultrasonography was able to identify parathyroid adenoma in those who had nonlocalizing or incorrectly localizing sestamibi scans. Additionally, ultrasonography provides information about concomitant thyroid pathology, described in 20% to 60% of bilateral neck explorations for parathyroid disease. In multigland disease, some studies have suggested that ultrasonography and sestamibi, even when combined, are poor localizing studies, unless combined with intraoperative parathyroid hormone (PTH) testing .

CT and MRI

CT and MRI may provide the surgeon with anatomic images with which they tend to be more familiar than ultrasonographic images. These imaging modalities have typically been secondary to ultrasonography and the functional studies discussed later. However, they may play a role in combination with other studies.

Some researchers have shown that MRI has similar sensitivity in detecting parathyroid tissue when compared with dual-phase technetium-99m sestamibi , whereas others have determined it is inferior to technetium-99m sestamibi/iodine-123 subtraction scintigraphy. CT scan has no specific application for parathyroid disease, but can be used in thyroid disease, specifically if the thyroid tissue still takes up iodinated contrast. This modality with contrast, however, can delay the future application of radioactive iodine therapy in those who have iodine-avid, well-differentiated thyroid cancer. Therefore, its application in isolation is limited.

Sestamibi

Radionuclide scintigraphy may be used for reoperative imaging of parathyroid disease, either adenoma or hyperplasia . Dual-phase technetium-99m sestamibi is based on the preferential retention of the radionuclide in the mitochondria of abnormal parathyroid tissue. Other agents, such as technetium-99 tetrafosmin, are also used. Imaging parameters may be altered to create uniplanar or multiplanar images, or even three-dimensional ones (sestamibi single-photon emission computed tomography [SPECT]). Subtraction imaging techniques to enhance parathyroid visualization may be used to reduce thyroid shadowing. Agents include thallium, technetium-99 pertechnetate, and iodine-123. Extensive literature exists supporting the use of sestamibi technology in parathyroid localization. Given the functional nature of the imaging, tissue may be located regardless of the surrounding anatomic concerns, although a differential in uptake between the parathyroid tissue and surrounding tissue is necessary.

Radioactive iodine

Radioactive iodine has long been used for diagnostic and therapeutic measures in thyroid carcinoma. This functional examination may detect thyroid tissue that is uptaking iodine for thyroglobulin production. Therefore, a few criteria must be met for imaging to be successful: the gland must be well-differentiated thyroid tissue that is still active in iodinization, and the tissue must not be iodine saturated (ie, currently uptaking iodine). If any of these criteria is not met, radioactive iodine imaging may fail to detect the thyroid tissue.

Hybrid studies

At this juncture, many surgeons are turning to hybrid imaging studies that use the anatomic resolution of CT and the tissue-functional detection of sestamibi and fluoro-2-deoxy-D-glucose (FDG). SPECT/CT and positron emission tomography (PET)/CT have emerged as helpful diagnostic tools in parathyroid and thyroid disease.

SPECT/CT uses merged images from a gamma camera and CT to create a study in which the functional parathyroid tissue can be well localized anatomically. The relationship of the parathyroid tissue with surrounding structures identified on the CT scan provides the surgeon with the information necessary to plan a curative surgery, which is particularly useful in the ectopic gland or revision situation, where typical landmarks are no longer useful or possibly not even present. Several studies have shown the usefulness and, in certain circumstances, superiority of SPECT/CT in localizing the offending gland .

PET/CT scans have begun to be used in recurrent thyroid carcinoma. This technique’s role continues to evolve, but a body of literature supports its use, particularly in certain circumstances. The prime example is a previously treated patient who has well-differentiated thyroid carcinoma and is experiencing increasing thyroglobulin levels but has a negative I-131 uptake scan. FDG-PET has been shown to detect non–iodine-avid thyroid carcinoma, with a diagnostic accuracy higher than those of other modalities . The addition of CT scan to the FDG-PET can alter patient management by better directing the surgeon to the exact foci of disease in as high as 48% to 67% of cases . Metastasis was detected in 95% of cases of well-differentiated thyroid cancer . This modality seems to be most effective if the thyroglobulin level reaches more than 10 ng/mL . The more precise localization that can be done preoperatively, the more focused the surgery can be, thus potentially limiting unnecessary dissection and risk to the cervical structures.