Case

 28 year old female patient presenting with thyroid

nodule of 5 months duration that has been
increasing in size

 Previously healthy with no history of neck radiation

 The nodule was first discovered upon self

palpation and was asymptomatic
• PMHx: negative

• PSHx: negative

• Meds: none

• Allergies: none

• Social Hx: non smoker, social drinker

• Family Hx: goiter (mother)

VS: WNL

PE: thyroid: no obvious swelling on inspection

left hemithyroid nodule ̴ 1 cm
non tender
fixed
smooth
No palpable LNs
 TSH: 1.010

 US done

 2 Left benign-looking hemithyroid nodules, larger one measuring

2x2x3cm

 Fine needle aspiration from the dominant nodule was performed

 FNA showed follicular cells with unclear significance

 Observation
 After 6 months follow up, US done showed increase in
size of nodule by 1 cm
 Repeat FNA showed papillary thyroid cancer
 No clinical positive lymph nodes
 Patient underwent total thyroidectomy with central lymph
node dissection
Anatomy and surgical implications:

- weighs between 15 and 20 g

- lower margin: near 4th or 5th tracheal rings

- bordered by the contents of the carotid sheath on each side

- thyroid sheath: expansion of pre-tracheal fascia

- ligament of berry: posteromedially, attachment of thyroid to tracheal rings, site of RLN injury

- arterial supply: superior thyroid arteries (originating from the external carotid arteries) and inferior
thyroid arteries (originating from the thyrocervical trunks)

- relationship of the ITA to the RLN: important landmark

- superior& middle thyroid veins internal jugular vein and inferior thyroid vein innominate or
brachiocephalic vein

Greenfield's Surgery: Scientific Principles and Practice, 5e > Chapter 75. THYROID GLAND
- RLN and the external branch of the superior laryngeal nerve

- right RLN: passes around subclavian artery

- left RLN: crosses aortic arch

- tubercle of Zuckerkandl: immediately lateral to and covers the RLN

- superior laryngeal: descends along the course of the internal carotid artery

- thyroid cancers with regional LN metastases: involve level VI lymph node metastases before involving
levels II, III, IV, and ultimately V

Greenfield's Surgery: Scientific Principles and Practice, 5e > Chapter 75. THYROID GLAND
Greenfield's Surgery: Scientific Principles and Practice, 5e > Chapter 75. THYROID GLAND
Laboratory tests:  

- thyroid dysfunction: directly, by measuring FT4 levels, or indirectly, by measuring TSH

- TSH: very sensitive and useful for early detection of thyroid dysfunction

- ↑ TSH & ↓ FT4: hypothyroidism vs. ↓ TSH & ↑ FT4: hyperthyroidism

- calcitonin: specific tumor marker for MTC

- Tg: tumor marker -- index of the amount of differentiated thyroid cancer post resection

 Kupferman ME, Patterson M, Mandel SJ, et al. Patterns of lateral neck metastases in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2004;130:857-860.
 THYROID IMAGING TECHNIQUES 

Ultrasonography

- evaluate the thyroid gland and its surrounding structures

- most sensitive and specific: determine the size, number, and distribution of thyroid nodules

- hyperechoic nodules: benign hypoechoic: malignant

- irregular margins: concern for malignancy

- FNA biopsy: - nodules greater than 1 cm

- concerning ultrasound features
- increased in size under serial US measurement

- preoperative planning, preoperative staging and postoperative F/U for recurrent DTC with negative iodine
uptake

Tan G, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226-231.
 
Cross-sectional Imaging

- large nodules firmly fixed or new vocal cord paralysis  concern for an invasive thyroid cancer

- large goiters with substernal component  define extent of goiter

Nuclear Medicine Imaging

Technetium Pertechnetate 99mTc Scintigraphy -- most commonly available for thyroid imaging

123
Iodine Scintigraphy -- indicate the functional characteristics of thyroid tissue

131
Iodine Scintigraphy. 131I concentrates in the thyroid by the same mechanism as 123I, but has a much longer half-
life (about 8 days)  isotope of choice for imaging of patients with DTC

Positron Emission Tomography -- limited to unusual circumstances such as recurrent thyroid malignancy

99m
Tc Sestamibi Scintigraphy

111
Indium-Octreotide Scintigraphy

Boi F, Lai ML, Deias C, et al. The usefulness of 99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. Eur J Endocrinol 2003;149:493-498.
Differential Dx for thyroid nodule:

benign vs. malignant

- adenomas
- colloid nodules
- congenital abnormalities
- cysts
- infectious nodules
- lymphocytic or granulomatous nodules
- Hyperplasia

vs.

- thyroid cancer
- parathyroid cancer
- mets to thyroid …
 FUNCTIONAL DISORDERS AND GENERAL TREATMENT CONSIDERATIONS 

Hyperthyroidism:

Symptoms: heat intolerance, sweating, palpitations, tremor, hyperphagia, thirst, sleep disturbances,
muscle wasting, atrial fibrillation, angina pectoris, or congestive heart failure

Graves disease. toxic diffuse goiter

- exophthalmos and palpitations
- autoimmune disorder with genetic predisposition
- female predominance (5-7 times)
- TSAbs

Toxic Multinodular Goiter. thyrotoxicosis

- endemic or nonendemic etiology

Solitary Toxic Adenoma. thyrotoxicosis plus dominant nodule

Lennquist S, Jortso E, Anderberg B, et al. Beta blockers compared with antithyroid drugs as preoperative treatment in hyperthyroidism: drug tolerance complications, and
postoperative thyroid function. Surgery 1985;98:1141-1146
Hypothyroidism:

can arise from intrinsic thyroid disease, iatrogenic thyroid removal or destruction, and antithyroid drug
effects
 
Hashimoto Thyroiditis. asa autoimmune thyroiditis, and lymphocytic thyroiditis
- 10% of the general population
- most common cause of goiter in US
- autoimmune with moderate genetic predisposition: (HLA)-DR3, -DR5, and -B8

Painless or Postpartum Thyroiditis.

Subacute Thyroiditis. virally related

Acute Thyroiditis. Bacterial

Amiodarone-induced Thyrotoxicosis or Thyroiditis.

Riedel Thyroiditis. fibrous thyroiditis

Tunbridge W, Brewis M, French JM, et al. Natural history of autoimmune thyroiditis. Br Med J Clin Res 1981;282:258-262.
 NODULAR THYROID DISEASE AND GENERAL TREATMENT CONSIDERATIONS
 
Solitary or Dominant Thyroid Nodule

- prevalence: 4% to 7%
- dominant nodule (largest or most apparent): dictates clinical decision making
- characteristics of a nodule assessed by physical examination (size, firmness, texture)
- more concerning for malignancy: - extreme of age
- uninodular
- fixation
- lymphadenopathy
- voice hoarseness
- hypothyroid state (if hyperthyroid  toxic nodule
negligible risk of malignancy)
- rapidly enlarging
- radiation exposure
- family history of thyroid cancer
- gender: not risk for malignancy

Enewold L, Zhu K, Ron E, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics. Cancer Epidemiol Biomarkers Prev 2009;18:784-791
- TSH required, then thyroid nodular disease is often assessed by US

- limited use of thyroid scintigraphy

FNA: - cornerstone of diagnostic evaluation of the thyroid nodule

- identify colloid nodules, benign nodular hyperplasia, thyroiditis, papillary thyroid carcinoma (PTC),
medullary thyroid carcinoma, and anaplastic thyroid carcinoma

- suggest an extranodal lymphoma, but usually more tissue for diagnosis and flow cytometry is
required

- classify nodules as follicular lesions or Hürthle cell lesions

- false-positive rate of 0% to 0.5% and a false-negative rate of 0% to 5%

Kebebew E, Clark OH. Differentiated thyroid cancer: "complete" rational approach. World J Surg 2000;24:942-951
THYROID MALIGNANCY AND GENERAL TREATMENT CONSIDERATIONS
 
- 98%: well differentiated  excellent long-term prognosis
- differentiated: follicular cell origin: - papillary thyroid carcinoma and its variants
- follicular thyroid carcinoma
- Hürthle cell carcinoma
parafollicular (C-cell) origin: - medullary thyroid carcinoma

- undifferentiated cancers such as anaplastic carcinoma

Papillary Thyroid Carcinoma. - 80%

- peak incidence: 3rd and 4th decades of life
- F>M
- papillary architecture, and associated with calcifications, psammoma
bodies, squamous metaplasia, and fibrosis
- cytology: large, overlapping nuclei that are optically clear (Orphan
Annie nuclei) and intranuclear grooves
- LN metastasis: 30% to 40%
- Distant metastases: 2% to 14%
- 70%: take up radioiodine
Microadenomas. - PTCs < 1 cm

Follicular Carcinoma. - 10% to 20%

- F>M
- 5th decade of life
- more advanced at the time of diagnosis compared with PTC
- more common to be locally infiltrative -- overall 10-year survival for patients with FTC is
slightly worse than for those with PTC
- hematogenous spread, with lung and bone most often being involved
- LN involvement: 10% of patients
- 80% will take up radioiodine

Minimally Invasive Follicular Carcinoma. - follicular neoplasms with capsular invasion but no vascular invasion

Emerick G, Duh QY, Siperstein AE, et al. Diagnosis, treatment, and outcome of follicular thyroid carcinoma. Cancer 1993;72:3287-3295.
Hürthle Cell Carcinoma. - 5%
- older patients
- if suggested by FNA cytology, a diagnostic thyroid lobectomy at the
minimum is required
- complete surgical resection: total thyroidectomy + central compartment
lymphadenectomy ± modified radical neck dissection

Medullary Carcinoma. - parafollicular C cells

- 5% to 7%
- 75%: sporadic fashion vs. 20% - 25%: familial (multiple endocrine neoplasia
[MEN] types 2A and 2B, as well as familial medullary thyroid carcinoma [FMTC])  
- more aggressive & more likely to metastasize
- 50% to 75%: LN mets
- distant mets: liver, lungs, and bones
- FNA: diagnostic for medullary cancer
- calcitonin is a very specific tumor marker

Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma. Recommendations for extent of node dissection. Ann Surg 1999;229:880-887
- total thyroidectomy + central compartment lymphadenectomy (level VI) ± MRND
- provocative testing (e.g., pentagastrin or calcium-stimulated calcitonin levels)
- genetic testing for RET proto-oncogene mutations

Skinner M, DeBenedetti MK, Moley JR, et al. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg 1996;31:177-181
 Anaplastic Carcinoma. - 1% to 2%
- rapidly growing firm thyroid mass)
- FNA + excisional bx
- aggressive resection ± adjuvant chemo-radiation

Thyroid Lymphoma. - < 5%

- majority: non-Hodgkin lymphomas of B-cell origin
- chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])
followed by radiation 

Metastases to the Thyroid Gland. - RCC (most common)

- melanoma
- GI, sarcomas…

Crevoisier R, Baudin E, Bachlot A, et al. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external
radiotherapy. Int J Radiat Oncol Biol Phys 2004;60:1137-1143
Greenfield's Surgery: Scientific Principles and Practice, 5e > Chapter 75. THYROID GLAND
 Management of Thyroid nodule
1-History
 Record the following information (Grade B; BEL 2):

• Age
• Family history of thyroid disease or cancer
• Previous head or neck irradiation
• Rate of growth of the neck mass
• Dysphonia, dysphagia, or dyspnea
• Symptoms of hyperthyroidism or hypothyroidism
• Use of iodine-containing drugs or supplements
 Most nodules are asymptomatic, and absence of

symptoms does not rule out malignancy

2-Physical Examination
 A careful physical examination of the thyroid gland and

cervical lymph nodes is mandatory

 Record
• Location, consistency, and size of the nodule(s)
• Neck tenderness or pain
• Cervical adenopathy
 3- Imaging: Ultrasound
 US evaluation is not recommended as a screening test in the
general population

 US evaluation is recommended for:

 Patients at risk for thyroid malignancy

 Patients with palpable thyroid nodules

 Patients with lymphadenopathy suggestive of a malignant

lesion.
 Describe position, shape, size, margins, content, echogenic
pattern, and vascular features of the nodule(s)

 Characteristics associated with malignancy

 hypoechoic pattern

 irregular margins

 more-tall-than-wide shape

 microcalcifications

 chaotic intranodular vascular spots

3- FNA biopsy
 FNA biopsy is recommended for nodule(s):
 Diameter larger than 1.0 cm that is solid and hypoechoic on US
 Any size with
• US findings suggestive of extracapsular growth or metastatic
cervical lymph nodes
• history of neck irradiation in childhood or adolescence;
• papillary thyroid carcinoma, medullary thyroid carcinoma , (MEN
2) in first-degree relatives;
• previous thyroid surgery for cancer
• increased calcitonin levels in the absence of interfering factors
Nodules that are hot on scintigraphy should be excluded from FNA
biopsy
 Incidentalomas detected by computed tomography (CT) or
magnetic resonance imaging (MRI) should undergo US
evaluation before consideration for FNA biopsy

 Incidentalomas detected by positron emission tomography

with 18F‑fluorodeoxyglucose should undergo US evaluation
plus UGFNA biopsy because of the high risk of malignancy
 Thyroid FNA Biopsy
 Clinical management of thyroid nodules should be guided

by the combination of US evaluation and FNA biopsy

(Grade A; BEL 3).

 Cytologic Diagnosis
• FNA biopsy results may be diagnostic (satisfactory) or
nondiagnostic (unsatisfactory).
4-Laboratory Evaluation in Patients with Thyroid Nodules
 Always measure TSH
 If TSH level is decreased, measure fT4 and total or fT3; if TSH level is
increased, measure fT4 and total or fT3 and anti–thyroid peroxidase
antibody (TPOAb)
 Assessment of serum thyroglobulin is not recommended in the
diagnosis of thyroid nodules. In patients undergoing surgery for
malignancy, serum thyroglobulin measurement may be useful to detect
potential false-negative results
 Measurement of basal serum calcitonin level may be a useful test in
the initial evaluation of thyroid nodules
 Measurement of calcitonin is mandatory in patients with a family
history or clinical suspicion of medullary thyroid carcinoma (MTC) or
MEN 2
 Thyroid scintigraphy
 Perform scintigraphy for a thyroid nodule or MNG if the

TSH level is below the lower limit or if ectopic thyroid

tissue or a retrosternal goiter is suspected
 131I thyroid uptake is not recommended for routine

diagnostic use unless low-uptake thyrotoxicosis is

suspected
 Management and Treatment

• For a patient with a thyroid goiter and local compressive symptoms offer
resection if the patient is a suitable surgical candidate

• Compressive symptoms: dyspnea, wheezing, cough, dysphagia, or a pressure

sensation that may be worse in the supine position

• For patients with a unilateral compressive mass and a benign biopsy, thyroid
lobectomy and total thyroidectomy are appropriate options

• For patients with bilateral goiter or nodules, total thyroidectomy usually is

recommended
• A patient with a thyroid nodule with a nondiagnostic biopsy (category 1)
should undergo repeat FNA under image guidance and with real-time
cytologic evaluation for sample adequacy.

• Some physicians favor waiting 3 months before repeat biopsy, but others
have found waiting to be unnecessary.

• For patients with nodules with persistently nondiagnostic biopsy, either

continued close clinical and sonographic follow-up or diagnostic lobectomy
may be elected based on patient preference and concern for malignancy
based on ultrasound findings
• For patients with a benign FNA biopsy finding (category 2), repeat ultrasound
should be performed

• For nodules with high sonographic suspicion, repeat evaluation should be

within 3 to 6 months

• For nodules with low to intermediate suspicion, ultrasound should be

repeated in 12 to 24 months

• For nodules with very low suspicion ultrasound findings and a benign FNA
specimen, it is reasonable not to repeat ultrasound; if ultrasound is repeated,
it should be performed at least 2 years later
 Levothyroxine Therapy for Benign Nodules
 Routine levothyroxine therapy is not recommended
 Levothyroxine therapy or iodine supplementation may be
considered in young patients with small nodular goiter and no
evidence of functional autonomy
 Levothyroxine therapy is not recommended for preventing
recurrence after lobectomy if TSH remains normal

 Surgical Indications for Benign Nodules

 Presence of local pressure symptoms
 previous external irradiation
 progressive nodule growth

 The preferred extent of resection for benign uninodular goiter is

lobectomy plus isthmectomy and for MNG is subtotal thyroidectomy
• For thyroid nodules with Bethesda System category 3 or 4 results,
mutation testing has been explored with the hope of definitively confirming
or excluding a malignancy: BRAF mutation and using a 167-gene
messenger RNA–based gene expression classifier

• Goal: avoid unnecessary surgery (e.g., diagnostic lobectomy for what

proves to be benign disease) and to be able to accomplish adequate
resection for malignancy in a single operation

• Primary critique ability to rule out malignancy with an adequate negative

predictive value (NPV) current role continues to be debated at the
present time

• Best current use of these tests is likely to guide a patient toward a more
complete resection when FNA would dictate diagnostic lobectomy, but
genetic testing is indicative of a malignancy

• The most recent American Thyroid Association guidelines do not

recommend either for or against these tests.
• One reasonable option for a Bethesda System category 3 lesion is repeat
biopsy

• Other options include close observation with ultrasound surveillance versus

diagnostic excision, typically in the form of a thyroid lobectomy

• The decision regarding which option to pursue involves consideration of

patient preference, ultrasound findings, and the whole clinical picture

• If genetic testing is used to inform this discussion, the above-described

considerations must be kept in mind and shared with the patient
• Bethesda System category 4 lesions: pursue diagnostic excision of these
lesions

• Ipsilateral thyroid lobectomy is recommended

• Total thyroidectomy rather than lobectomy include lesions that are greater
than 4 cm, lesions with contralateral nodules, or lesions with other
concerning clinical features such as prior significant radiation exposure

• The results of genetic testing, if performed, also may sway the surgeon
and the patient to pursue total thyroidectomy

• If lobectomy is performed, the patient also must accept the need for
ongoing surveillance of any disease present in the contralateral lobe
• Bethesda System category 5 lesions typically are managed surgically
similar to lesions with biopsy results that are diagnostic of malignancy

• Category 6 lesions are diagnostic of malignancy, and the management of

thyroid malignancy is total thyroidectomy
Management of Thyroid Nodules During Pregnancy

 Thyroid nodules in pregnant women should be managed in the same

way as in nonpregnant women; in the presence of suspicious clinical or
US findings, diagnosis necessitates FNA biopsy

 Avoid use of radioactive agents for both diagnostic and therapeutic

purposes

 During pregnancy, suppressive levothyroxine therapy for thyroid nodules

is not recommended

 If FNA biopsy shows a follicular lesion, surgery may be deferred until

after delivery
Management of FNA Biopsy–Malignant Nodules During Pregnancy

 When a thyroid malignancy is diagnosed during the first or second

trimester, thyroidectomy may be done during the second trimester

 During the third trimester, surgical treatment can be deferred until the
immediate postpartum period
Thyroid nodule in children

 Evaluation of nodular disease in children is similar to that in adults

 Surgery is often necessary for cold, as well as hot nodules

 Treatment of Thyroid Cancer

- Thyroidectomy: primary treatment for DTC

- Advantages of total thyroidectomy over lobectomy

(a) removal of multifocal intrathyroidal tumors
(b) use of radioiodine to localize and treat small amounts of residual normal thyroid tissue,
and more importantly, regional or distant metastases
(c) after radioiodine ablation, use of serum thyroglobulin as a sensitive marker of persistent or
recurrent disease

- Patients with PTC >1 cm who underwent total thyroidectomy have a significantly lower risk of
recurrence and lower mortality compared with those undergoing thyroid lobectomy

 Cooper D, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006;16(2):109-142.
 Lymphadenectomy
Patients with clinically positive lymph nodes, or those found to have
micrometastases by FNA or frozen section

Prophylactic CCLND:
 metastatic disease to CCLN can be found in up to 60% of patients with
clinically negative LNs
 American Thyroid Association management guidelines: routine CCLND
be considered for patients with papillary thyroid cancer and Hürthle cell
cancer if it can be done without increasing morbidity
 residual subclinical disease, as indicated by postoperative serum
thyroglobulin levels, can be decreased using this strategy
 Decrease recurrence but no survival benefit for for use of CCLND
 Incidence of RLN injury and hypoparathyroidism is not increased
 diminish the higher risk of damage to nerves or parathyroid glands that is
associated with reoperation for a local recurrence
Radioiodine Therapy

- After thyroidectomy:
- low doses: to demonstrate remaining thyroid tissue or metastatic disease
- higher doses: for ablation or therapy

- TSH should be at least 30 mIU/ml

- To minimize the duration of hypothyroid symptoms, give T3 until 2 weeks prior to scanning,
- as T3 has a much shorter half-life (8 to 12 hours) than T4

- Provides decreased rate of recurrence and increased disease-specific and overall survival

- Postoperative RAI is commonly used, even for lower-risk cancers, and thyroid remnant ablation is
generally accepted as part of the postoperative treatment of patients who have undergone total or
near-total thyroid excision for DTC

- intrathyroidal cancers smaller than 1 cm without evidence of metastatic disease are not treated with
radioiodine because of low potential for local or distant recurrence

- If only a lobectomy is performed, radioiodine ablation is possible only 25% of the time because of the
volume of residual tissue and its avidity for RAI
Mazzaferri E. Thyroid remnant 131 I ablation for papillary and follicular thyroid carcinoma. Thyroid 1997;7:265-271.
Thank You