5. ENT Thyroid Gland 2014A

8/17/2019 5. ENT Thyroid Gland 2014A

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1 of 7 |Page Guevara, Guiang, Harris, Hwang; Andrade (editor)

September 19, 2012

Thyroid land

Dr. Lago

OUTLINE

1. History and Introduction

2. Anatomy of the Thyroid Gland

3.

Physiology of the Thyroid Gland

4. Diffuse Thyroid Disease

a. Goiter

b. Hypothyroidism

c.

Hyperthyroidism

5. Evaluation of an Ant. Neck mass

6. Thyroid Carcinoma

HISTORY AND INTRODUCTION

Thyroid gland is an endocrine (ductless) gland

First described by Thomas Wharton in 1656 (also discovered the

submandibular gland)

Secretes substance that lubricates the trachea

Cosmetic

Chemical substance is Thyroxine

o Stimulates O2 consumption of most cells of the body

o Helps regulate lipid and carbohydrate metabolism

o Necessary for growth and maturation

Essential for life

o Absence – poor resistance to cold temperature, mental and

physical slowing. In children, mental retardation/dwarfism

o Excess – body wasting (metabolic acceleration resulting in rapid

consumption of body energy and substrates), nervousness,

tachycardia, tremors, excess heat production

ANATOMY OF THE THYROID GLAND

[2013B]

Composed of 2 lobes connected by the isthmus at the level of the 2nd

and 3rd

tracheal rings (sites of tracheostomy)

o Isthmus of the thyroid gland covers the first few tracheal rings [Boies]

o Thyroid lobes rest on the lateral tracheal wall and may even extend up

onto the thyroid alae [Boies]

Located on the anterolateral portion of the trachea, just below the larynx

o Thyroid gland is located below the cricoid cartilage

Located underneath the anterior muscles of the neck:

o Sternohyoid – most anterior

o Sternothyroid

Thyrohyoid (technically does not pass over the thyroid)

Situated in the muscular triangle of the neck

o Boundaries

Hyoid bone

Omohyoid

Sternocleidomastoid

[Boies]

A normal thyroid gland is normally not palpable

o Palpable mass in the midline compartment of the neck (between the

sternocleidomastoid muscles and overlying the larynx and upper

trachea) that move up and down with swallowing represent thyroidabnormality

o Firm, discrete nodules are more likely to contain malignancy

o Abnormalities of vocal cord function or the presence of palpable lymph

nodes suggest malignancy

HISTOLOGY

Follicular Cells

o Simple cuboidal epithelium surrounding a colloid-filled lumen

o

Acini are filled with pink-staining proteinaceous material

(colloid)

Thyroid cell functions:

o Collect and transport iodine

o Synthesize thyroglobulin and secrete into the colloid

o Remove the thyroid hormones from the thyroglobulin secreting

them into the circulation

BLOOD SUPPLY[2013B]

Superior Thyroid Artery (from the ECA) supplies the upper pole of the gland

Inferior Thyroid Artery (from the thyrocervical branch of the Subclavian

Artery)

VENOUS DRAINAGE[2013B]

Superior, Inferior, and Middle Thyroid veins

LYMPHATIC DRAINAGE[2013B]

Risk for metastasis into the:

o Central Jugular Nodes (Levels 2, 3, and 4)

o Pretracheal Nodes

o Paratracheal Nodes

NERVOUS SUPPLY

Superior Laryngeal Nerve is in close proximity to the superior thyroid a.

ligate at the area proximal to the thyroid to avoid hitting the nerve [2013B].

Injury can lead to low-frequency vocal range and inability to sing higher

notes [Probst]


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Recurrent Laryngeal Nerve branch of the vagus nerve that passes alongside

the trachea. Injury may cause paralysis of the true vocal cords [2013B]

resulting to hoarseness [Probst]

PARATHYROID GLANDS

[2013B] Located at the back of the thyroid gland at the superior pole and middle

portion.

4 in total 2 on each side

Yellowish in color resembling fat on dissection

Accidental resection leads to hypocalcemia tetanus

May be implanted in other tissues such as the SCM

EMBROYOLOGY

First seen as a ventral midline diverticulum of the floor of the pharynx just

caudal to the junction of the 1st

and 2nd

branchial arches at the site known as

the foramen cecum [Boies]

o Day 24: median epithelial thickening appears in the floor of the

ectodermal pharyngeal gut, dorsal to the future tuberculum impar

[Probst]

Thyroid migrates caudally along a tract that passes ventral to the body of thehyoid, then curves underneath it and downward to the level of the cricoids

cartilage [Boies]

o End of 7th

week: Thyroid gland reaches pre-tracheal position and

thyroglossal duct obliterated or resorbed [Probst]

THYROGLOSSAL DUCT CYST

Vestigial remnants of thyroglossal duct tract [Boies] due to incomplete

obliteration or resorption of the thyroglossal duct [Probst]

Usually tense, firm, midline swelling [Probst] found anywhere between the

base of the tongue and superior border of the thyroid gland that elevates

with swallowing and slide upward when tongue is protruded [Boies]

75% are manifested before 5 years of age and most are diagnosed before 12

months [Probst]

Papillary carcinoma has been reported within thyroglossal duct cysts [Boies],

but malignant transformation is rare [Probst]

Treatment:o Antibiotic therapy (to treat any inflammation/infection) [Boies]

o Complete excision of cyst and thyroglossal duct tract wi th removal of the

central portion of the hyoid bone to prevent recurrence [Boies]

PHYSIOLOGY OF THE THYROID GLAND

THYROTROPIN RELEASING HORMONE (TRH)

Produced by the hypothalamus

Release is pulsatile, circadian (9pm-12am) [2013B]

Travels through the portal venous system to the thyrotropic

cells of the adenohypophysis (anterior pituitary)

Stimulates production and release of thyrotropin (TSH)

Down-regulated by T4

THYROID STIMULATING HORMONE (TSH)

Produced by the adenohypophysis

Travels through the portal venous system to cavernous sinus, body

Stimulates several processes

o Synthesis and release of T3, T4

o Growth of the thyroid gland

Up-regulated by TRH

Down-regulated by T4, T3

THYROID HORMONES

Regulated by the hypothalamic-pituitary gland axis [2013B]

Majority of circulating hormone is T4

o T4 – 98.5%

o T3 – 1.5%

Total hormone load is influenced by serum binding proteins

o Thyroid binding globulin (TBG) – 70%

o Albumin – 15%

o Transthyretin – 10%

Regulation of thyroid hormone production is based on the free

component of thyroid hormone

THYROID HORMONE SYNTHESIS

IODINE – raw material essential for thyroid hormone synthesis

T4 and T3o Synthesized in the colloid by iodination and condensation of

tyrosine molecules bound to TG

Thyroglobulin (TG)

o Synthesized in the thyroid cells

o Excreted into the colloid by cell extrusion (exocytosis) of

granules that also contain an enzyme – thyroid peroxidise

o Hormones remain bound to TG until these are secreted

Iodide iodine (active form) iodine + tyrosine MIT and DIT T3

(MIT+DIT) and T4 (DIT + DIT) binds with thyroglobulin stored within

follicle lumen [2013B]

When secreted

o Colloid is engulfed or ingested by the thyroid cells

o Peptide bonds are hydrolyzed

o

Free T4, T3 are released into the capillarieso Enzyme splitting of the thyroxine from TGB by lysosomes and

endosomes TGB released back into cells and T3 and T4 into the blood

[2013B]

FUNCTION OF THE THYROID HORMONES

Increase sensitivity of target tissues to catecholamines

Promote:

o Lipolysis

o Glycogenolysis

o Gluconeogenesis

Metabolism

o INCREASED:


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Sensitivity to catecholamines

Basal metabolic rate

Carbohydrate, protein and lipid metabolism

o Normal growth: Increased bone turnover

Normal development

o Especially CNS development (fetal brain and skeletal

maturation)

Regulation of:

- Synaptogenesis

-

Neuronal Integration- Myelination

- Cell Migration

Endocrine system:

o INCREASE in serum GLUCOSE

o DECREASE in serum CHOLESTEROL

CVS:

o Inotropic effects (increase CO)

o Chronotropic effects (increase HR)

Reproduction: Fertility requires normal thyroid function

GIT: Stimulates gut motility

DIFFUSE THYROID DISEASE[Boies]

May be due to:

o Goiter

o Thyroiditis

Inflammatory lesions of the thyroid

Tenderness

Signs and symptoms of inflammation

o Hyperthyroidism

o Grave’s disease

o Advanced carcinoma

GOITER[2013B]

General term for enlargement of the thyroid gland

Not a disease

Can be NODULAR or DIFFUSE

HYPOTHYROIDISM HYPERTHYROIDISM

Puffy Skin

Sluggishness, lowered vitality

Weight GAIN

COLD intolerance

Insomnia

Muscle pain and spasm

Bradycardia

Decreased Libido

Brittle Nails

Profuse sweating

Irritability

Weight LOSS

HEAT intolerance (abnormally

high temperature)

Muscle pain and weakness

Tachycardia

High BP

Exophthalmia – if uncontrolled

Hypothyroidism – reduction in the rate of oxidative energy-releasing

reactions within the body cells

Hyperthyroidism – increase in metabolic rate

Most of these conditions are medically treated [2013B]

CRETINISM

Manifestation of hypothyroidism in children which may result in

mental retardation, dwarfism, permanent sexual immaturity anddeafness [2013B]

TREATMENT

Hyperthyroidism

o Partial removal or by partial radiation (destruction of the gland)decrease the levels of hormone release [2013B]

o Several drugs that inhibit thyroid activity (lifetime management) [Boies]

EVALUATION OF ANTERIOR NECK MASS

[2013B]

Most common reason for consult: anterior neck mass

Decide on either medical or surgical treatment

o Hyperthyroid/Hypothyroid usually treated medically

o

Euthyroid may be medically treated or surgically managed ENTs – Surgical treatment

Endocrinologists – Clinical/Medical treatment

Most have clinically evident signs and symptoms, some look normal

(subclinical variants); Subclinical – may not exhibit symptoms

Hyperthyroid Hypothyroid

Euthyroid

First do hormone testing. If found to be hypothyroid/hyperthyroid treat

medically. If euthyroid evaluate and do thyroid scan. If it is a warm nodule,

then it is most likely benign and so do suppression. If it is a cold nodule there is

high probability of being malignant so do a thyroid ultrasound and do FNAB if

necessary [2013B]

THYROID EVALUATION

*Pituitary Hypo/Hyperthyroidism = Primary Hypo/Hyperthyroidism↑ / ↓ – refer to endo; Euthyroid – work-up (poss. malignancy or surgery)

TSH

Why requested?

o Suspicion of hyperthyroidism/hypothyroidism

o Presence of goiter or nodules

o Monitor response to therapy

o Screening for thyroid dysfunction in certain risk groups (previous

thyroid surgery, DM, history of neck irradiation)

Best assessment of the integrity of Hypothalamic-Pituitary-Thyroid

axis, due to improvements in assays

o Above 0.5 mu/ml – Hyperthyroidism

o Below 0.3 mu/ml – Hyperthyroidism

o

Normal Range: 0.3-0.5 mu/ml Patients with abnormal results are referred to endocrinologists [2013B]

ENTs only manage patients with normal TSH [2013B]

FREE T3 AND T4

Gives an accurate reflection of thyroid hormone production [2013B]

FT4 is more commonly used because it also reflects FT3 levels (TBG common

binding site) [2013B]

Free T4 (FT4) – measures concentration of free thyroxine which is

the only biologically active fraction in serum

Bound thyroxine does not have an effect on pituitary TSH secretion

o Free thyroxine is the only one that has reflex effect on TSH

secretion

TSH

INCREASED

Serum FT4

Increased

PituitaryHypothyroidism

Decreased

Hypothyroidism

DECREASED

Serum FT4

Increased

Hyperthyroidism

Decreased

PituitaryHyperthyroidism

NORMAL

Euthyroid


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Free T4 is not affected by changes in concentration of binding

proteins, thus conditions like pregnancy, estrogen or androgen

therapy does not affect FT4 levels

TOTAL T3/T4

T3 measures concentration of triiodothyronine in the serum

T4 measures concentration of thyroxine

Test measures both bound and unbound forms

Bounded therefore no direct correlation with metabolic state

Can be affected by changes in the levels of the thyroid binding

globulins, albumin levels. Conditions such as use of contraceptive

pills, acute liver disease will increase binding proteins

RADIOACTIVE IODINE UPTAKE (RAIU)

Measurement of iodine uptake by the thyroid gland from the

extracellular pool over a set period of time

Useful in indicating hyperthyroid states

THYROGLOBULIN

10% normal individuals

15-30% CA patients

Not reliable [2013B]; Best for follow-up on CA after thyroidectomy

Determines remnant thyroid cells after thyroidectomy [2013B]

THYROID SCINTIGRAPHY/THYROID SCAN

Radionuclide imaging of the thyroid

One of the earliest procedures developed in nuclear medicine

Not preferred for work-up of neck mass because test takes a lot of

preparation (radioactive tracer) and is only available in certain

institutions

Uptake studies involve the measurement of the amount of tracers

extracted by the thyroid at specific times

o Concentrated in the thyroid gland which allows visualization of

the gland

The most commonly used radioactive tracers are isotopes of iodine

(I-123, I-131) and technetium pertechnetate (Tc99-m)

o Of the three, technetium pertechnetate can be used with

children because of its short imaging time and less radiationexposure

o Radioactive iodine is administered orally and reaches the

follicular lumen in 20-30 minutes

I-131 has a half-life of 8 days compared to I-123 which has a

half-life of 13 hours

- Higher particulate emission on the gland

- Stays in the body for a longer period of time

Alternative is Tc99-m with a half-life of only 6 hours

- Low particulate emission - Short imaging time and lessened exposure to radiation [2013B]

- Good for children

Is read either as hot (increased uptake) or cold (decreased uptake) nodules

depending on the thyroid gland uptake of the tracer [2013B]

Suspected thyroid nodule

Thyroid scan

“ HOT” “COLD” Multinodules

nodules nodules

Hormone Suppression Ultrasonography Signs of Clinically

Malignancy Benign

Biopsy

Approx. 80-85% are “cold” with 14-22% of them malignant whichneeds surgical treatment [2013B]

5% are “hot” with a 2cm, chances are it will not change in sizeo If ineffective or signs of malignancy appear, then surgery is necessary

[Boies]

10-15% are warm

Scan is 89-93% sensitive but only 5% specific

Indications:

1.

Identification of functional solitary nodules when initial serumthyrotropin is decreased

2. If FNAB findings show "follicular" neoplasm or "suspicious"

results, the finding of a “hot” nodule may decrease the risk of

malignancy

3.

Detecting neck metastasis

ULTRASOUND

Ultrasound – sound is reflected back

Test is easily accessible, so preferably used for work-up of neck mass

Can detect small nodules (


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o Non-diagnostic fine needle aspirate (as an adjunct for repeat

FNAB)

UTZ

Cystic Solid

FNAB

Malignant Suspicious Benign

FINE NEEDLE ASPIRATION BIOPSY (FNAB)

The single most helpful test to establish the nature of a solitary

nodule (benign or malignant? what kind of malignancy? )

o Gauge 20-25 needle with local anesthetic used (BUT Sir

personally uses a 23 gauge needle without local anesthesia) 10cc, 23 gauge needle – mass is punctured and aspirated to about 4-

5mm pressure [2013B]

o 4-5 separate skin punctures into the nodule to obtain an

adequate specimen for examination

o Must have an experienced cytopathologist

o Extremely safe and inexpensive

o Large "core" needle biopsy (gauge 18,19,21) [2013B]

Increased complication, size limitation, andadditional info vs. FNAB

Not used by Doc: he says that large bore needles tend to

aspirate blood (bloody tap)

Accuracy rates range from 50-90% with a low false positive (90%

4 RECOGNIZED CATEGORIES FOR FNAB

1.

Malignant

2.

Benign

3. Suspicious

4.

Insufficient

RESULTS THAT WARRANTS A SUSPICIOUS LABEL

1.

Hurthle Cell Neoplasm

2.

Follicular variant of papillary carcinoma

3. Low-grade papillary carcinoma

4. Hashimoto's disease

MANAGEMENT ALGORITHM ACCORDING TO FNAB RESULTS

BENIGN

o Is unpredictable therefore needs close observation

o Repeat FNAB after 6-24 months

o Thyroid suppression benefits in five separate studies given at

doses ranging from 100-200μg proved to be not significant in

shrinking nodules especially those >2cm in size [2013B]

MALIGNANT

o Is more straightforward for the predictive value for a positive

FNAB is close to 100% and the specificity is 100%

o Surgery is warranted

SUSPICIOUS

o Includes follicular and Hurthle cell neoplasm

o Limiting factor of FNAB

o Malignancy rate accounts for only 10-20%

o Surgical management is indicatedo Look for poor clinical indicators, if there are presence of poor indicators

it is more likely malignant [2013B] and warrants surgery if malignant Age (60)

Gender (Male)

Prior Radiation

Family History

Pain

Compressive or invasive features

Cervical metastasis

Size (>4cm)

Rapid Growth

INSUFFICIENT

o Requires a repeat FNAB under ultrasound guidance

THYROID SUPPRESSION

1.

Administer Levothyroxine 2. Maintain TSH levels at


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o Orphan Annie Sign: prominent nucleoli

Peak incidence – 3rd decade of life

Female to Male ratio 3:1

Propensity to spread to lymph nodes in 30-50% of patients

o Lymph node metastasis has no effect on survival

o Presence of lymph nodes may indicate papillary carcinoma

Late metastasis to lungs and bones

Multicentricity seen in 30-60% of patients (higher rate seen in

irradiated patients) – Do not remove just one lobe, remove other lobes[2013B]

Favorable prognosis

5 year survival rate: 90-95%

Occult, incidental thyroid CA (50 years old

Death from papillary CA depends on:

o Age >50 years

o Tumor size and grade

o Initial extent of disease

PATTERNS OF LATERAL NECK METASTASIS IN PAPILLARY CA

Level 1 14%

Level II 52%

Level III 57%

Level IV 41%

Level V 21%

Most metastasis found within the deep cervical lymph nodes

Levels II-V are most commonly involved so selective neck

dissections(SND) II, III, IV, and V is the treatments of choice

Location of Positive Nodes # of Cases

Middle Jugular 85

Lower Jugular 67

Upper Jugular 50

Posterior Cervical 22

Superior Mediastinum 7

Submandibular 4

Haagensen CD et al 1972

FOLLICULAR CARCINOMA

Occur in older patients, typically age 40-60 years

Female to male ratio probably nearly equal

Propensity for angioinvasion and hematogenous spread

Lymph node metastasis are not a prominent feature and only occur

after angioinvasion is seen

Distant metastasis to lungs and bones seen in 50-65% of patients,

and are detected and treated by radioactive iodine I-131 following

total thyroidectomy

Categories:

a. Low-grade: encapsulated, well-differentiated

b. High-grade: angioinvasive and Hurthle Cell CA

10-year survival rate 30-85% depending on tumor grade and

category, BUT NOT on tumor size (Avg = 70%)

Differentiate from follicular adenoma by capsular, vascular, or

stromal invasion. Differentiation is difficult by frozen section and

impossible by FNAB

These tumors concentrate Iodine I-131 quite well, but may lose thischaracteristic with older patients resulting in a worse prognosis

TREATMENT OF DIFFERENTIATED THYROID CARCINOMAS

Controversy involves extent of necessary thyroid resection and

degree of lymph node dissection

o Papillary CA – total thyroidectomy + LN dissection

o Follicular CA – total thyroidectomy

Some data suggest similar survival with total thyroidectomy vs.

ipsilateral thyroid lobectomy and isthmectomy

Treat all patients with papillary or follicular CA with exogenous

thyroid hormone or lifelong TSH suppression. Serum TSH levels

should be nearly undetectable, but toxicity should be avoided

TOTAL THYROIDECTOMY

Treatment for multicentric disease (30-80%)

Probable lower recurrence rate Use Iodine I-131 and thyroglobulin post-operatively

Low incidence of recurrent nerve paresis/hypoparathyroidism

THYROID LOBECTOMY

Avoid hypoparathyroidism and bilateral recurrent nerve injury

Reliance on similar survival data

Difficult, if not impossible, to use Iodine I-131 post-operatively to

treat local and/or distant metastasis fol lowing ablation with Iodine I-

131


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RADIOACTIVE IODINE THERAPY

Relies on the thyroid tissue’s affinity for iodine uptake in treating

residual or metastatic disease

May give large dose of Iodine I-131 and spare surrounding non-

thyroid tissue from injury

PRIMARY use is in patients following total thyroidectomy

Indicated in ALL patients with LN or distant metastasis

Maybe used selectively in patients with Thyroid CA confined to the

thyroid gland following total thyroidectomy

Discontinue all exogenous thyroid hormone for 3-4 weeks and

confirm preparation by elevated serum TSH

EXTERNAL IRRADIATION

Appears useful only in selected locally invasive thyroid CA (usually

aggressive follicular tumors) and anaplastic CA

CHEMOTHERAPY

Has limited to no usefulness at present

MEDULLARY THYROID CARCINOMA (MTC)

Originally described by Hazard and associates in 1959

Solid histologic pattern with amyloid in its stroma and calcification

seen

In 1967, MTC discovered in association with calcitonin-secreting

parafollicular C cells of neural crest origin (ultimobranchial body) in

the thyroid gland

Elevated levels of serum calcitonin are usually present in MTC and

form a reliable marker for the presence of occult MTC in familial

cases and recurrent MTC in previously treated patients

LN metastasis, detected in 50% of patients, have an adverse effect

on survival and are treated with modified radical neck dissection Systemic metastasis is not responsive to radiation and MTC does not

concentrate Iodine I-131. The usefulness of chemotherapy

(Adriamycin and Cisplatin) is limited

Diarrhea, increased intestinal motility, and elevated calcitonin may

be the first sign of recurrent MTC

ANAPLASTIC CARCINOMA

Uncommon thyroid malignancy affecting older patients

May arise from a well-differentiated thyroid CA

80% of patients have a history of a long standing goiter with sudden

rapid growth, hoarseness, dysphagia, and airway compromise

Tracheal invasion and/or bilateral recurrent nerve paralysis can

be seen

Poor prognosis, usually results in 100% death when diagnosed , with

mean life expectancy of 6-9 months

Death occurs from local invasion of vital cervical structures and

airway compression

Surgical excision is rarely possible without sacrificing essential

cervical structures, but tissue diagnosis is needed for differentiating

it from a lymphoma. Usually do not operate anymore

Tracheostomy and total thyroidectomy are both extremely difficult

External radiation may temporarily control the local effects of

the malignancy

Limited effect from systemic chemotherapy (Adriamycin);

No hormonal manipulation known

References:

2013B Trans, Recording, Lecture, Probst, Boies

5. ENT Thyroid Gland 2014A

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