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17 Thyroid andParathyroid Diseases
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• Inferior thyroid artery from thyrocervical trunk from subclavian artery
Venous drainage (3 vessels)
• Inferior, middle, and superior thyroid veins→internal jugular and/or brachioce-
phalic vein
Lymphatic drainage
• Dominant drainage to level VI
• Secondary drainage basins: precricoid, delphian, paratracheal, pretracheal,
perithyroidal
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Nerves
• Recurrent laryngeal nerves→enter at cricothyroid joint
– Left: around aorta→ascends in tracheoesophageal groove
– Right: around subclavian artery→ascends in tracheoesophageal groove
– Relationship with inferior thyroid artery
Branching patterns highly variable
Nerve generally anterior to artery
Nerve posterior to artery (50% of patients on left)
Nerve between branches of artery (50% of patients on right)
– Simon triangle → assists in triangulating the recurrent nerve
intraoperatively
Common carotid artery laterally
Esophagus medially
Inferior thyroid artery superiorly
– A non-recurrent laryngeal nerve occurs in approximately 0.5–1% of cases
• Superior laryngeal nerve
– Originates at nodose ganglion→divides at hyoid cornu
– Internal branch: sensation to supraglottis and pyriform sinus
– External branch: motor innervation to inferior constrictor and cricothy-
roid muscles
– Joll’s triangle→assists inlocating the external branch of the superior laryn-
geal nerve intraoperatively
Superior thyroid pole/vessels laterally
Sternothyroid muscle anteriorly
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N. M. Phan et al.
Histology
• Composed of follicles (single layer of epithelial cells) surrounding a col-
loid matrix
• Iodine important for synthesis→thyroid hormone stored bound to thyroglobulin
(made in the liver)→unbound and released into circulation
– T3: potent form, half-life is 1 day, majority converted in periphery
– T4: correlates with TSH levels, half-life 6 days
Benign Thyroid Disease
Hyperthyroidism
• Grave’s disease→autoimmune, TSH receptor antibody→stimulation
• Toxic nodule/multi-nodular goiter→Hyperthyroidism symptoms when nodule
is >3cm
• Thyroiditis→most common cause of painful thyroid
• Exogenous hyperthyroidism
• Thyrotropin
Treatment ofHyperthyroidism
• Propylthiouracil/methimazole
• Iodides
• Beta-blockers
• Radioactive iodine
• Thyroidectomy
• Graves: total thyroidectomy (thyroid storm precautions)
• Toxic nodules: ipsilateral lobectomy
Hypothyroidism
• Hashimoto’s thyroiditis→most common cause hypothyroidism→antithyroid
peroxidase (antimicrosomal antibodies, anti-TPO, and anti-Tg)
• Iodine deciency
• Radiation induced
• Iatrogenic/postsurgical
• Drug (lithium, iodine)
• Central hypothyroidism
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Malignant Thyroid Disease
Epidemiology
• Incidence of thyroid malignancy is 5–15%, with 90% being papillary and fol-
licular cancers
Risk factors for thyroid malignancy
History of radiation exposure Family history of thyroid carcinoma
Single dominant nodule >4cm Male gender
Age <20 and >70 Cervical nodules
Vocal fold immobility Firmness to palpation
Classication
Papillary Thyroid Carcinoma
• Most common well-differentiated carcinoma
• Derived from follicular cells, form papillae, “Orphan Annie eye” nucleus, and
psammoma bodies
• Typically multicentric both within ipsilateral and contralateral lobe
• Lymphatic spread→ cervical node metastasis possible: rates of 62% central
nodes and 25% lateral nodes
• Histologic subtypes with worse prognosis: tall cell, columnar cell, diffuse
sclerosing
Follicular Thyroid Carcinoma
• May exhibit minimal or wide vascular invasion, which affects prognosis
• Primarily hematogenous or direct spread with little lymphatic invasion
Hurthle Cell Carcinoma
• Tend to be older patients (60s)
• Variant of follicular carcinoma, oxyphilic cells noted
• Aggressive in nature, spread via lymphatics or hematogenous
• Increased risk for distant metastasis (30%), with 40% bone and 30% lung
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Medullary Thyroid Carcinoma
• Carcinoma of parafollicular C cells: sporadic (worse prognosis) and familial type
• Genetic component→RET testing recommended→multiple endocrine neopla-
sia (MEN) IIa and IIb
• Typically multifocal and metastatic disease noted
Anaplastic Thyroid Carcinoma
• 2% of all thyroid carcinomas, but 15–39% of all deaths
• Aggressive rapidly growing inltrative thyroid mass, vocal cord paralysis
• Tend to be older patients (50–60s)
• Metastasis possible to lungs, liver, bones within weeks
• FNA typically shows necrosis and degeneration
• Survival rates low (20%) at 1 year
Work-Up
• Laboratory studies
– TSH levels with reexive T3/4
– Serum calcitonin levels if concerned about medullary thyroid cancer
• Imaging
– Ultrasound: allows identication, characterization, and trending of nodules,
central and lateral lymphadenopathy
American Thyroid Association (ATA) and American College of Radiology
(ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) are two
different systems that use ultrasound patterns to predict cancer risk in thyroid nodules
• ATA Nodule Risk of Malignancy, Sonographic Patterns, and FNA guidance
– High suspicion (>70–90%)
Recommend FNA at ≥1cm for nodules that are hypoechoic nodule (partially cystic) with irregular margins, microcalcications, taller than wide
shape, rim calcications, or evidence of extrathyroidal extension (ETE)
– Intermediate suspicion (>10–20%)
Recommend FNA at ≥1cm for nodules that are hypoechoic nodule with
smooth margins without microcalcications, ETE, or taller than wide shape
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– Low suspicion (5–10%)
Recommend FNA at ≥1.5cm for nodules that are isoechoic or hyperechoic
nodule with eccentric solid areas without microcalcication, irregular margin or ETE, or taller than wide shape
– Very low suspicion (>3%)
Consider FNA at ≥2cm vs. observation for nodules that are spongiform or
partially cystic nodules without any of the sonographic features described
in low, intermediate, or high suspicion patterns
– Benign (<1%)
No FNA recommended for purely cystic nodules (no solid component)
TI-RADS radiographic features on sonography from 5 categories
Composition: Echogenicity
Cystic or spongiform : 0 points Anechoic: 0 points
Mixed cystic and solid: 1 point Hyper- or isoechoic: 1 point
Solid or almost completely solid: 2 points Hypoechoic: 2 points
Very hypoechoic: 3 points
Margin: Shape:
Smooth or ill-dened: 0 points Wider than tall: 0 points
Lobulated/irregular: 2 points Taller than wide: 3 points
Extrathyroidal extension: 3 points
Echogenic foci:
None or large comet-tail artifact: 0 points
Macrocalcications: 1 point
Peripheral/rim calcications: 2 points
Punctate echogenic foci: 3 points
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• TI-RADS Scoring, Classication, and Recommendations
– One score is assigned from each of the categories
– Predominantly cystic or spongiform nodules are benign with no further
points added
TR1: 0 points are considered benign nodules, no FNA required
TR2: 2 points are considered not suspicious nodules, no FNA required
TR3: 3 points are considered mildly suspicious nodules, for ≥2.5 cm
FNA is recommended, ≥1.5 cm follow-up is recommended at 1, 3,
and 5 years
TR4: 4–6 points are considered moderately suspicious nodules, for
≥1.5cm FNA is recommended, ≥1.0cm follow is recommended at 1, 2, 3,
and 5 years
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TR5: ≥7 points are considered highly suspicious nodules, for ≥1.0 cm
FNA is recommended, ≥0.5cm follow is recommended annually for up
to 5 years
– Ultrasound-guided ne-needle aspiration (FNA): improves diagnostic yield
after selection of appropriate nodules to aspirate
Cytopathology reported as a diagnostic category-based Bethesda System
2017 Bethesda System for Reporting Thyroid Cytopathology
Risk of
Diagnostic category
I.Nondiagnostic/unsatisfactory 1–4 Repeat FNA with US
II.Benign 0–3 Clinical follow-up
III. Atypia of undetermined signicance/follicular
lesion of undetermined signicance
IV. Follicular neoplasm or suspicious for
follicular neoplasm
V.Suspicious for malignancy 60–75 Surgical lobectomy or
VI.Malignant 97–99 Near-total thyroidectomy
malignancy (%) Management
5–15 Repeat FNA, molecular
testing
15–30 Surgical lobectomy,
molecular testing
near-total thyroidectomy
• Molecular proling recommended for thyroid nodules with indeterminate cytology (Bethesda III–IV), with over 112 gene panel linked to thyroid cancer (BRAF,
N-/H-/K-RAS, RET/PTC, and PAX8/PPARc genes account for 70% of known
mutations)
• Bethesda III: if positive lobectomy recommended, if negative active surveillance
or diagnostic lobectomy
• Bethesda IV: if positive total thyroidectomy recommended, but if negative should
be managed by at least a diagnostic lobectomy
• Fiber-optic laryngoscopy: all patients should have vocal cords assessed
preoperatively
Staging
Important items which confer greater risk are age >50, male, distant metastasis,
non-papillary pathology (i.e., tall cell, anaplastic), advanced local disease/extracapsular extension.
TNM staging for thyroid carcinoma
T1A Tumor diameter ≤1cm or smaller
T1B Tumor diameter >1≤2cm
T2 Primary tumor diameter >2 to ≤4cm
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TNM staging for thyroid carcinoma
T3A Primary tumor diameter >4cm limited to thyroid
T3B Primary tumor diameter >4cm, with gross extrathyroidal extension invading only strap
muscles
T4A Tumor of any size extending beyond thyroid capsule, invading subcutaneous soft tissue,
larynx, trachea, esophagus, recurrent laryngeal nerve
T4B Tumor invades prevertebral fascia or encases carotid artery, mediastinal nerves
NX Nodes not assessed at surgery
N0 No metastatic nodes
N1A Metastasis to level VI (pretracheal, paratracheal, prelaryngeal) or VII (upper mediastinal)
N1B Metastasis to unilateral or bilateral or contralateral cervical (levels I, II, III, IV, V)
M0 No distant metastasis
M1 Distant metastasis
Patient <55 years old Patient ≥55 years old
Stages for differentiated thyroid cancer
Stage I Any T, Any N, M0 T1, N0, M0
Stage II Any T, Any N, M1 T1-2, N1, M0
T3A/T3B, any N, M0
Stage III T4A, any N, M0
Stage IVA T4B, any N, M0
Stage IVB Any T, Any N, M0
Stages for anaplastic carcinoma
Stage IVA T1-T3A, N0/Nx, M0
Stage IVB T1-T3A, N1, M0
Stage IVC Any T, Any N, M1
Stages for medullary carcinoma
Stage I T1, N0, M0
Stage II T2-T3, N0, M0
Stage III T1-T3, N1A, M0
Stage IVA T4A, any N, M0
Stage IVB T4B, any N, M0
Stage IVC Any T, Any N, M1
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Risk Stratifying Systems
AMES—age, metastases, extent of primary cancer, tumor size
High-risk features:
• Age: males >41, females >51
• Metastases: distant metastases
• Extent: papillary with extrathyroidal spread or follicular with major capsule
invasion
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• Size: ≥4cm
Overall survival:
• Low risk—98% (95% disease-free survival (DFS)). High risk—54% (45% DFS)
AGES—age, tumor grade, tumor extent, tumor size
• Age <40, has better prognosis
• Grade: pathologic grade of tumor
• Extent: extent of primary tumor
• Size: <4cm has better prognosis
• Prognostic score=0.05×age in years (except in pts <40, then y=0)
– + 1 (grade 2)
– +3 (grade 3 or 4)
– +1 (if extrathyroidal)
– +3 (distant mets)
– + 0.2 × tumor size in cm
• Risk categories—0–3.99, 4–4.99, 5–5.99, >6 (median is 2.6)
20-year survival:
• <3.99 (99%), 4–4.99 (80%), 5–5.99 (33%), >6 (13%)
MACIS—metastasis, age, completeness of resection, invasion, size
N. M. Phan et al.
• Prognostic score=3.1 (age<40 years) or 0.08×age (if >40)
– + 0.3×tumor size in cm
– + 1 (if incompletely resected)
– +1 (if locally invasive)
– +3 (if distant mets)
• Risk categories—0–6, 6–6.99, 7–7.99, >8
20-year survival:
• <6 (99%), 6–6.99 (89%), 7–7.99 (56%), >8 (24%)
Management
Papillary Thyroid Carcinoma
• High risk: distant disease, extrathyroidal papillary cancer, capsular invasion, age
>40 (men) and >50 (female)
• Total thyroidectomy: >4cm, gross extrathyroidal extension (ETE), cN1 or cM1
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• Hemithyroidectomy: <4cm without extrathyroidal extension, cN0 and cM0
• Can consider lobectomy for microPTC <1cm, without extrathyroidal extension,
cN0 and cM0
• Central compartment and paratracheal neck dissection with+nodal disease or in
high-risk patients
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Follicular Thyroid Carcinoma
• Partial thyroidectomy with pathologic evaluation, if carcinoma proceed to completion thyroidectomy
• Spread via hematogenous or direct extension, may eliminate the need for elective
or prophylactic neck dissection
Hurthle Cell Carcinoma
• Total thyroidectomy
• Central neck dissection in the presence of+nodal disease
Medullary Thyroid Carcinoma
• Family RET genetic testing and counseling
• Total thyroidectomy with central neck dissection+selective neck dissection
• With+lateral disease, imperative to perform level II–V
• Postoperative neck ultrasound, calcitonin, and CEA testing
Anaplastic Thyroid Carcinoma
• BRAF mutation analysis: signicant percentage of cases harboring activating
point mutations of the BRAF oncogene allowing for targeted therapy, other
mutations include RAS and p53 b-catenin
• Aggressive multimodal therapy early stage: total thyroidectomy, intensitymodulated radiation therapy (IMRT), and adjuvant chemotherapy
• Palliative therapy (tracheostomy controversial due to poor prognosis) for
advanced lesions
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Postsurgical Management
Radioactive Iodine
• For differentiated thyroid cancer, indicated for remnant ablation, adjuvant therapy, treatment of residual or metastatic disease
• Facilitates monitoring of thyroglobulin levels
• Some controversy for routine use postoperatively regarding utility and dosage,
some risk of associated hematologic malignancy
TSH Suppression
• Suppression of TSH, using supraphysiologic doses of levothyroxine (LT4) commonly used to decrease the risk of recurrence, though optimal goal of TSH must
be balanced with adverse effect of TSH suppression (subclinical thyrotoxicosis)
• High-risk cancer patients with incomplete response to therapy, TSH should be
maintained below 0.1mU/L indenitely, while patients with excellent response
to therapy, serum TSH levels should be maintained between 0.1 and 0.5mU/L
for up to 5 years, after which the degree of TSH suppression can be reduced
• Intermediate risk cancer patients with incomplete response to therapy, TSH
should be maintained between 0.1 and 0.5mU/L
• Low-risk cancer patients with excellent response to therapy, who have undergone
ablation with undetectable/low serum Tg levels, TSH should be maintained at the
lower end of normal (0.5–2 mU/L)
Surveillance
• Serum thyroglobulin measured every 6–12 months
• Neck ultrasounds examining surgical bed, central, and lateral lymph nodes
Parathyroid
Embryology
• Development starts at fth week of development
• Derived from endoderm of third and fourth pharyngeal pouches
• Inferior glands arise from third pouch and migrate with thymus
• Long descent→large area of possible ectopic placement
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