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Chapter 75

Thyroid Gland

David T. Hughes and Paul G. Gauger

Key Points

1 The tubercle of Zuckerkandl is an anatomic feature of the thyroid that helps facilitate identification

of the recurrent laryngeal nerve (RLN) and the superior parathyroid gland.

2 A nonrecurrent right laryngeal nerve is most commonly due to anomalous origin of the right

subclavian artery from the distal aortic arch which then passes posterior to the esophagus (arteria

lusoria); a left non-RLN is rare and due to situs inversus.

3 Ultrasound is the imaging procedure of choice for nodular thyroid disease, and surgeon-performed

ultrasound helps facilitate operative planning.

4 The Bethesda Classification System for Thyroid FNA can guide further management of thyroid

nodules.

5 Additional thyroid resection or adjuvant treatment with radioiodine is seldom required for an

incidental papillary microcarcinoma (<1 cm) found in the surgical specimen.

6 Molecular markers including BRAF, RET, and RAS can aid in the diagnosis of thyroid cancer on fineneedle biopsy and in the management of thyroid cancer.

7 Genotype/phenotype correlation using the specific RET protooncogene mutation identified in each

patient/family can help determine the appropriate age for prophylactic thyroidectomy in patients

with hereditary medullary thyroid carcinoma.

8 Lymphoma of the thyroid or anaplastic thyroid cancer should be considered in the hypothyroid

patient who experiences rapid growth of the thyroid.

9 Advantages of total thyroidectomy over thyroid lobectomy for differentiated thyroid carcinoma

include (a) removal of multifocal intrathyroidal tumors; (b) facilitation of radioiodine imaging and

ablation for residual, regional, or metastatic disease; and (c) use of serum thyroglobulin as a

sensitive marker of persistent or recurrent disease.

10 Therapeutic, compartment-based lymph node dissection is indicated for patients with evidence of

lymph node metastasis in thyroid cancer.

The broad indications for thyroidectomy include hyperthyroidism, thyroid nodularity, thyroid goiter,

Graves disease, thyroid cancer, and prophylaxis in multiple endocrine neoplasia type 2. Understanding

of the embryology, anatomy, physiology, and relevant pharmacology of thyroid disease and precise

surgical technique and careful attention to detail are necessary to prevent complications of thyroid

surgery.

EMBRYOLOGY AND SURGICAL IMPLICATIONS

Developmental Embryology

The thyroid is mostly derived of endoderm from the ventral embryologic digestive tract and is the first

endocrine gland to develop. A midline diverticulum arises in the area of the foramen cecum at the base

of the tongue at approximately 4 weeks of gestation. The tissue descends as the median thyroid

component and ultimately becomes the isthmus and the majority of each lateral lobe. The foramen

cecum ruptures and resorbs during week 6 of gestational age, leaving behind a regressive fibrous

thyroglossal duct (including the portion associated with the central hyoid bone). The distal end of the

thyroglossal duct tract persists as a recognizable pyramidal lobe attached to the isthmus in about 30% to

50% of individuals. The lateral thyroid components develop from the caudal pharyngeal endoderm

(with contribution from the fourth and fifth branchial pouches) and arise later in development than the

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median component.1 The lateral components become increasingly removed from the pharynx, leaving a

tapering connection on each side, which eventually detaches. The residual posterolateral projection

from the lateral thyroid component is known as the tubercle of Zuckerkandl. Because of its branchial

pouch origin, the lateral thyroid component is closely associated with the superior parathyroid anlage

(from the fourth pouch). The lateral components contain C cells (from neural crest origin) which

migrate into the superolateral portion of the lobes and eventually secrete calcitonin. The unified thyroid

begins to differentiate into thyroid follicles between 8 and 11 weeks. Thyroid hormone production

begins on a cellular level by the third month of gestation when iodine trapping occurs.

Congenital Abnormalities

A lingual thyroid gland is an uncommon developmental malformation of thyroid tissue erupting from

the base of the tongue due to failure of the median thyroid component to descend from the foramen

cecum. Treatment of lingual thyroid can include exogenous thyroid hormone to suppress thyroidstimulating hormone (TSH), radioiodine ablation or surgical excision. Thyroglossal duct cysts occur in

the midline of the neck along the path of descent of the median thyroid component. They may occur

from the base of the tongue to the low central neck, although most are located just inferior to the hyoid

bone. Although they are often discovered during infancy and childhood, it is not uncommon for them to

present in adulthood – discovered either because of mass effect or infection. Elevation of the mass with

protrusion of the tongue is very suggestive of a thyroglossal duct cyst. Resection of a thyroglossal duct

cyst involves excision of the entire thyroglossal duct, the cyst, and the tract as it courses through the

central portion of the hyoid bone (Sistrunk procedure). The epithelial lining usually contains some

thyroid cells and thyroid carcinomas (usually of papillary type) can arise along the thyroglossal duct

tract.

Ectopic thyroid tissue can be found in other areas of the central cervical compartment and the

mediastinum. These can be extrathyroidal nodules associated with multinodular goiters or embryologic

rests of thyroid tissue along the path of caudal migration.2 Historically, the concept of lateral aberrant

thyroid tissue was used to describe follicular thyroid tissue in the carotid sheath or the lateral

compartments of the neck; however, it is now generally agreed that this cannot occur as an embryologic

abnormality and rather this represents a regional nodal metastasis of differentiated thyroid cancer

(DTC).

ANATOMY AND SURGICAL IMPLICATIONS

A normal thyroid gland weighs between 15 and 20 g. The thyroid isthmus is approximately 1 to 2 cm in

transverse and vertical dimensions and normally overlies the trachea from just below the cricoid

cartilage to the fourth or fifth tracheal ring. The lateral lobes lie adjacent to the thyroid cartilage and

cricothyroid muscle as well as the lateral trachea and a portion of the lateral esophagus on each side.

The two lobes are roughly conical and normally measure ∼5 cm in craniocaudal and 2 to 3 cm in

mediolateral and anteroposterior dimensions.

Muscular, Fascial, and Airway Relationships

The thyroid lies in the central compartment of the neck bordered by the contents of the carotid sheath

on each side. The anterolateral surface is covered by the sternothyroid muscles, which do not

completely meet in the midline above the level of the isthmus. Superficial to the sternothyroid muscles

are the sternohyoid muscles that meet at the median raphe which is typically split during

thyroidectomy. These muscles are innervated on the inferolateral aspect by the ansa cervicalis (ansa

hypoglossi). The thyroid is invested in a thin layer of connective tissue that is an expansion of the

pretracheal fascia (often called the “thyroid sheath”). The sheath is not to be confused with the thyroid

capsule, which is more integral to the gland itself. The plane between the capsule and the sheath is

usually easy to develop as the thyroid is mobilized away from surrounding structures. Especially near

the superior portion of the thyroid, the sheath defines a coronal plane that, when opened, exposes the

potential space between the pharynx/esophagus and the cervical vertebral bodies. The sheath is

condensed as the anterior suspensory ligament above the isthmus. The sheath also attaches the posterior

surface of the thyroid gland to the tracheal rings and is condensed posteromedially into the ligament of

Berry on each side. The ligament of Berry is a firm attachment to the trachea near the cricothyroid

space and is often intimately associated with the recurrent laryngeal nerve (RLN) near its insertion at

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the cricopharyngeus muscle. The RLN is most vulnerable to iatrogenic injury when dividing the

ligament of Berry.

Vascular Relationships

The thyroid gland has a very high blood flow index per tissue mass and receives its arterial supply from

a paired system of superior thyroid arteries (originating as the first branch of the external carotid

arteries) and inferior thyroid arteries (originating from the thyrocervical trunks). The superior artery

courses along the inferior pharyngeal constrictor muscle group and branches near the tip of the superior

pole of the thyroid, usually into at least an anterior and posterior branch. The inferior thyroid artery

(ITA) courses behind the carotid artery and then crosses medially to meet the thyroid lobe just below

the ligament of Berry near the tracheoesophageal groove. The ITA has multiple branches that course in

a plane between the sheath and the capsule of the gland. The relationship of the ITA to the RLN is an

important landmark and the specific relationship between the ITA and the RLN (anterior, posterior, or

interdigitated) may be variable and caution should be taken in ligation of the ITA branches during

thyroidectomy. Occasionally, an arteria thyroidea ima arises from the aorta or innominate artery and

courses anterior to the trachea to directly serve the inferior portion of the thyroid gland.

Venous drainage of the thyroid is by a widely anastomosing system that condenses into three main

trunks. The superior thyroid veins course adjacent to the superior thyroid arteries but empty into the

internal jugular vein at the level of the carotid bifurcation. Middle thyroid veins are present in more

than half of patients and drain laterally to the internal jugular vein. These veins are divided early in the

course of mobilizing the thyroid lobe. In tracing a vessel laterally, if it passes anterior to the carotid

artery, it is a middle thyroid vein, whereas if it passes posterior to the carotid, it is the ITA. The inferior

thyroid veins form nearly all of the vascular connections found at the inferior poles of the thyroid lobes

and are situated anterior to the RLN. The number and configuration of these veins can be quite variable,

but in general they descend along the course of the thyrothymic tract to drain into the ipsilateral

brachiocephalic vein.

Neurologic Relationships

1 Two nerves have critical importance during thyroidectomy: the recurrent laryngeal nerve (RLN) (also

known as the inferior laryngeal nerve) and the external branch of the superior laryngeal nerve (EBSLN).

The right RLN arises from the vagus at the level of the subclavian artery and passes (recurs) around the

posterior aspect of the artery before ascending into the central compartment. The right RLN takes an

oblique course in the central neck and may be 1 to 2 cm lateral to the trachea low in the central neck

before traveling toward its entry point at the cricothyroid. The left RLN arises from the vagus nerve as

it crosses the aortic arch posterior to the ligamentum arteriosum. It passes inferior and medial to the

arch and ascends to the larynx in the tracheoesophageal groove along a course that is typically linear

and more vertical than the right RLN. The RLN often lies immediately posterolateral to the ligament of

Berry, but it is not infrequent that it can be embedded in the fibrous connections of the ligament itself,

especially the anterior branch if the RLN bifurcates outside the larynx. In a standard anatomic

relationship, the tubercle of Zuckerkandl lies immediately lateral to and covers the RLN (Fig. 75-1). An

uncommon, but high-risk, anatomic arrangement occurs when the RLN is found lateral to the tubercle of

Zuckerkandl (Fig. 75-2). If the surgeon is unaware of this possibility (which may exist when the

tubercle has undergone nodular enlargement), the nerve is subject to iatrogenic injury.3 Up to 34% of

RLNs will bifurcate proximal to the inferior border of the cricoid cartilage with the anterior branch

containing the motor fibers and the posterior branch containing sensory fibers.4 Injury to these branches

can lead to hoarseness and aspiration due to motor and sensory dysfunction respectively, manifesting as

hoarseness and/or aspiration.

Figure 75-1. The standard anatomic relationship whereby the recurrent laryngeal nerve (RLN) passes medial to the tubercle of

Zuckerkandl before its insertion into the cricothyroid interval.

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Figure 75-2. The uncommon but high-risk anatomic variation where the recurrent laryngeal nerve (RLN) courses lateral to the

tubercle of Zuckerkandl, which is often enlarged. The nerve is encountered much earlier in the dissection required for

thyroidectomy and is at risk of being misidentified as a vascular structure.

2 It is critical to be aware of the occasional non-RLN (also called a “direct” laryngeal nerve). This

anomaly results from abnormal embryonic development of the aortic arch. The anomaly is more

common on the right (approximately 0.5% to 0.7%) than on the left (approximately 0.04%). 5 On the

right, a nonrecurrent nerve is the consequence of the formation of the arteria lusoria vascular

abnormality, in which the innominate artery is absent and the right common carotid and right

subclavian arteries originate directly from the arch. The right subclavian artery arises as a branch of the

aortic arch distal to the left subclavian and takes a retroesophageal course. This anomaly can produce

dysphagia due to compression of the esophagus between the posterior trachea and the subclavian artery

termed dysphagia lusoria. A nonrecurrent left RLN requires a right-sided aortic arch (as occurs in situs

inversus viscerum), the origin of the left subclavian artery abnormally sited on the aortic arch, and the

displacement of the ligamentum arteriosum to the right and thus is a rarely found anomaly.

The superior laryngeal nerve (SLN) arises from the vagus at the nodose ganglion near the base of the

skull and descends along the course of the internal carotid artery. At the level of the hyoid bone, it

bifurcates into the internal branch (which enters the larynx at the thyrohyoid membrane to provide

sensory innervation to the superior larynx) and the external branch (which provides motor innervation

to the cricothyroideus muscle which contributes to variation in voice pitch and projection). The external

branch has a variable course in relation to the inferior pharyngeal constrictor muscle and the branches

of the superior thyroid artery which makes it vulnerable to iatrogenic injury. The Cernea classification

of the anatomic variations of the SLN are depicted in Figure 75-3.6

Lymphatic Relationships

Lymph flows in multiple directions through a rich plexus surrounding the thyroid. The thyroid gland has

intracapsular lymph channels, which provide some communication between lobes across the isthmus.

The central compartment (level VI) nodal basin is comprised of the pretracheal and paratracheal nodes

and those along the RLNs between the carotid sheaths laterally and extends from the hyoid bone

cranially and to the level of the innominate artery caudally.7 Within the anterior suspensory ligament

near the pyramidal lobe is a small group of midline prelaryngeal lymph nodes known as the Delphian

nodes. The lateral cervical nodal basins include the upper jugular (level II), midjugular (level III), and

lower jugular (level IV) lymph nodes as well as the posterior triangle lymph nodes (level V) (Fig. 75-4).

Thyroid cancers with regional lymph node metastases tend to involve level VI before involving levels II,

III, IV, and ultimately V.8 Level I (submental) and level VII (superior mediastinal) involvement is less

common but can occur. Documented cases of “skip” metastases directly to the lateral compartment with

no level VI involvement have been reported but are atypical.9

Figure 75-3. Cernea classification of the anatomic relationships between the external branch of the superior laryngeal nerve

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