Thyroid diseases

HYPERTHYROIDISM
Diffuse Toxic Goiter (Grave’s Disease)
Definition
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Autoimmune
Strong familial predisposition
Female preponderance (5:1)
Peak incidence (40-60 years)
Characteristics
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Thyrotoxicosis
Diffuse goiter
Extrathyroidal conditions
– Ophthalmopathy
– Dermopathy (pre-tibial myxedema)
– Thyroid acropachy
– Gynecomastia
Possible Triggers
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Postpartum state
Iodine excess
Lithium therapy
Bacterial and viral infections
Genetic Factors
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HLA-B8
HLA-DR3
DLADQA1*0501
HLA-DRB1*0701 – protective
CTLA-4
CD40
PTPN22 – encodes lymphoid tyrosine
phosphatase
CD25 – encodes for IL-2Ra
Associated Diseases
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DM Type 1
Addison’s Disease
Pernicious anemia
Myasthenia gravis
Macroscopic Features
Diffusely and smoothly enlarged
Increased vascularity
Microscopic Features
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Hyperplastic gland
Columnar epithelium
Minimal colloid
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Nuclei exhibit mitosis
Papillary projections of hyperplastic
epithelium
Aggregates of lymphoid tissue
Increased vascularity
Clinical Features
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Hyperthyroid symptoms
– Heat intolerance
– Increased sweating and thirst
– Weight loss
Increased adrenergic stimulation
– Palpitations
– Nervousness
– Fatigue
– Emotional lability
– Hyperkinesis
– Tremors
GI symptoms
– Increased frequency of bowel
movements
– Diarrhea
Females
– Amenorrhea
– Decreased fertility
– Increased incidence of miscarriages
Children
– Rapid growth with early bone
maturation
Adults
– Cardiovascular complications like
atrial fibrillation and CHF
Physical Examination
Weight loss
Facial flushing
Skin is warm and moist
Darkening of the skin (African-American)
Tachycardia or atrial fibrillation with
cutaneous vasodilation
Fine tremor
Muscle wasting
Proximal muscle group weakness with
hyperactive tendon reflexes.
Thyroid is diffusely and symmetrically
enlarged
Bruit or thrill over the gland
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Loud venous hum in the supraclavicular
space
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Other features that might develop
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Ophthalmopathy
– More common in smokers.
– Lid lag (von Graefe’s sign)
– Spasm of the upper eyelid
(Dalrymple’s sign)
– Prominent stare (due to
catecholamine excess)
– Periorbital edema
– Conjuctival swelling and congestion
(chemosis)
– Proptosis
– Limitation of upward and lateral gaze
(from involvement of the inferior and
medial rectus muscles, respectively)
– Keratitis
– Blindness
Dermopathy
– Deposition of glycosaminoglycans,
leading to thickened skin in the
pretibial region and dorsum of the
foot.
Gynecomastia
– Common in young men
Rare bony involvement
– Leads to subperiosteal bone
formation and swelling in the
metacarpals (thyroid acropachy)
Oncholysis
Diagnostic Tests
Suppressed TSH with or without an
elevated FT4 or FT3.
Other tests are not needed if eye signs
are present.
Iodine 123
– If eye signs are not present.
– Confirmation: elevated uptake with a
diffusely enlarged gland.
Technetium scintigraphy
– To determine etiology.
FT3
– Determined if FT4 is normal.
Anti-Tg and Anti-TPO
– Elevated (75% of patients)
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– Not specific
TSH-R or TSAb
– Diagnostic
– Increased in 90% of patients.
CT or MRI
– In the orbits
– To evaluate Grave’s opthalmopathy
Treatment
Antithyroid Drugs
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Administered in preparation for RAI
ablation or surgery.
Inhibits the organic binding of iodine and
the coupling of iodotyrosines.
Propylthiouracil
– 100-300mg, 3x a day
– Inhibits peripheral conversion of T4
to T3.
– Useful in thyroid storm.
– Preferred in pregnant and
breastfeeding women because
methimazole is associated with
congenital aplasia.
Methimazole
– 10-30mg, 3x a day, then OD.
Most patients have improved symptoms
in 2 weeks and become euthyroid in
about 6 weeks.
Some physicians use the block-replace
regimen, by adding T4 (0.05-0.10mg) to
prevent hypothyroidism and suppress
TSH secretion.
Relapse occurs if discontinued.
Curative treatment is reserved for
– Small, nontoxic goiters 90bpm.
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Propanolol (20-40mg, 4x a day)
Consider calcium channel blockers if
beta blockers are contraindicated.
– Exercise caution in patients with
asthma.
Radioactive Iodine Therapy (Iodine 131)
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Mainstay of treatment in North America
Most patients become euthyroid after 2
months.
Small increased risk for nodular goiter,
thyroid cancer, and hyperparathyroidism.
Unexplained increase in CVS mortality
rates.
Most often used in older patients with
small or moderate-sized goiters.
Those who have relapsed after medical
or surgical therapy.
Those in whom antithyroid drugs and
contraindicated.
Absolute contraindications
– Pregnant or planning pregnancy
within 6 months of treatment.
– Breastfeeding
Relative contraindications
– Young patients
– Thyroid nodules
– Opthalmopathy
The higher the initial dose, the earlier the
onset and the higher the incidence of
hypothyroidism.
Surgical Treatment
In North America, it is indicated when RAI
is contraindicated.
– Have confirmed cancer or suspicious
thyroid nodules
– Young
– Planning pregnancy
– Severe reactions to antithyroid
medications
– Have large goiters (>80g)
– Reluctant to undergo RAI therapy.
Relative contraindications
– Smokers or patients with moderate
to severe Grave’s ophthalmopathy.
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Desiring rapid control of
hyperthyroidism with a chance to be
euthyroid.
– Those with poor compliance to
antithyroid medications.
– Pregnancy
➔ Perform in the 2nd trimester
Should only be done when rapid control
is needed and antithyroid medications
can’t be used.
Goal should be the complete and
permanent control of the disease.
Patients should be euthyroid before
operation with antithyroid drugs that
should be continued up to the day of
surgery.
If it is not possible to render the patient
euthyroid prior to surgery (if the surgery
is urgent or the patient is allergic to
antithyroid medications), the patient can
be prepared with β-blockade and
potassium iodide alone. Steroids can be a
useful adjunct in this situation.
Total or near-total thyroidectomy
– Procedure of choice
– Coexistent thyroid cancer
– Refused RAI therapy
– Had severe ophthalmopathy or lifethreatening reactions to medications.
– Patients had higher rates of
temporary hypoparathyroidism.
Subtotal thyroidectomy
– Leaving a 4-7g remnant
– Recommended for all remaining
patients.
– Remnant tissue may be left
bilaterally
– Or total lobectomy on one side and
subtotal on the other (HartleyDunhill procedure). Fewer
complications.
– Prone to recurrence.
Toxic Multinodular Goiter
Characteristics
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Usually in older individuals who have a
prior history of a nontoxic multinodular
goiter.
Hyperthyroidism
– May become apparent when patients
are placed on low doses of TH
suppression for the goiter.
– Can be precipitated by iodidecontaining drugs such as contrast
media and the antiarrhythmic agent
amiodarone.
Some may have T3 toxicosis.
Others may only have atrial fibrillation or
CHF.
S/Sx similar to Grave’s but
extrathyroidal manifestations are
absent.
Diagnostic Studies
Blood tests are similar to Grave’s.
Decreased TSH and elevated FT3 or FT4.
Increased RAI uptake, showing multiple
nodules with increased uptake and
suppression of the remaining gland.
Treatment
RAI
– For elderly patients with poor
operative risks, no airway
compression from the goiter and
thyroid cancer is not a concern.
Surgical resection
– Near-total or total thyroidectomy to
avoid recurrence.
– Identify RLN found laterally on the
gland and anteriorly over a nodule.
Toxic Adenoma
Characteristics
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From a single hyperfunctioning nodule.
In younger patients.
Somatic mutations in the TSH-R gene.
Physical examination
– Solitary thyroid nodule without
palpable thyroid tissue on the
contralateral side.
RAI
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Hot with suppression of the rest of
the gland.
Antithyroid medications and RAI
– For smaller nodules
– Larger nodules may require higher
doses, leading to hypothyroidism.
Surgery
– Lobectomy
– Isthmusectomy
– For younger patients and those with
larger nodules.
Thyroid Storm
Characteristics
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Hyperthyroidism
Fever
CNS agitation or depression.
CVS and GI dysfunction.
Hepatic failure
Triggers
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Abrupt cessation of antithyroid
medications.
Infection
Thyroid or nonthyroid surgery
Trauma in patients with untreated
thyrotoxicosis.
Amiodarone
Exposure to iodinated contrast agents
Following RAI therapy
Treatment
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Beta blockers to reduce peripheral T4 to
T3 conversion.
Oxygen supplementation
Hemodynamic support
Non-aspirin compounds for pyrexia
Lugol’s iodine or sodium ipodate IV
– To decrease iodine uptake and
thyroid hormone secretion.
PTU therapy
– To block the formation of new
thyroid hormone.
– Reduces T4 to T3 conversion
Corticosteroids
– To prevent adrenal exhaustion
– Block hepatic thyroid hormone
conversion.
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HYPOTHYROIDISM
Clinical Features
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Cretinism and characteristic facies
– Failure of the gland to develop or
function in utero.
Failure to thrive
Severe mental retardation
Childhood or adolescence development
– Delayed development
– Abdominal distention
– Umbilical hernia
– Rectal prolapse
Adults
– Tiredness
– Weight gain
– Cold intolerance
– Constipation
– Menorrhagia
Facial and periorbital puffiness
– Severe hypothyroidism or myxedema
– Deposition of glycosaminoglycans
Skin is rough and dry and often develops
a yellowish hue from reduced conversion
of carotene to vitamin A.
Hair is dry and brittle
Severe hair loss may occur
Loss of the outer two-thirds of the
eyebrows
Enlarged tongue may impair speech
Impaired libido and fertility
Cardiovascular changes
– Bradycardia
– Cardiomegaly
– Pericardial effusion
– Reduced cardiac output
– Pulmonary effusion.
If hypothyroidism occurs due to pituitary
failure
– Pale, waxy skin
– Loss of body hair
– Atrophic genitalia
Laboratory Findings
Primary hypothyroidism
– Low T3 and T4
– High TSH
Secondary hypothyroidism
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Low T3 and T4
Low TSH that do not increase with
TRH stimulation
Thyroid autoantibodies are highest in
– Autoimmune diseases (Grave’s,
Hashimoto’s).
– Nodular goiter
– Thyroid neoplasms
ECG
– Decreased voltage
– Flattening or inversion of T waves.
Treatment
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T4
– Treatment of choice
– 50-200 ug per day
– 100 ug starting dose, but 25-50 ug for
elderly patients and those with heart
diseases and profound
hypothyroidism.
Get a baseline ECG before treatment if
hypothyroidism is severe.
If patient presents with myxedema coma
– Initial emergency treatment with
large doses of T4 (300-400ug).
THYROIDITIS
Acute (Suppurative) Thyroiditis)
Characteristics
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Infection of the gland through
– Hematogenous or lymphatic route
– Direct spread from persistent
pyriform sinus fistulae or thyroglossal
duct cysts
– A result of penetrating trauma to the
gland
– Immunosuppression
Streptococcus and anaerobes account for
70% of cases.
More common in children.
Preceded by an upper respiratory
infection or otitis media.
Characterized by severe neck pain
radiating to the jaws or ear, fever, chills,
odynophagia, and dysphonia.
Complications that may occur:
– Systemic sepsis
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Tracheal or esophageal rupture
Jugular vein thrombosis
Laryngeal chondritis
Perichondritis
Sympathetic trunk paralysis
Diagnosis
Leukocytosis on blood tests and FNAB for
GSCS and cytology.
CT Scan
– May help to delineate the extent of
infection and identify abscesses.
Children with recurrent acute thyroiditis
– Suspect a persistent pyriform sinus
fistula.
Sensitivity of identifying fistulae
– Barium esophagography (50%)
– CT (80%)
– Direct endoscopy (100%)
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Treatment
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Parenteral antibiotics
Drainage of abscesses
Thyroidectomy
– Persistent abscesses
– Failure of open drainage
Complete resection of the sinus tract,
including the area of the thyroid where
the tract terminates
– If with pyriform sinus
– To prevent recurrence
Subacute Thyroiditis
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Characteristics
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Painless or painful.
Exact etiology is unknown.
Genetic predisposition
– HLA-B35
One model of pathogenesis suggests that
viral or thyroid antigens, when presented
by macrophages in the context of HLAB35, stimulate cytotoxic T lymphocytes
and damage thyroid follicular cells.
Painful Thyroiditis
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Viral
Postviral inflammatory response
30-40 year old women.
Sudden or gradual onset of neck pain
which may radiate to the mandible or
ear.
Gland is enlarged, tender, and firm.
Four stages
1. Initial hyperthyroid phase – due
to release of thyroid hormone.
2. Euthyroid phase
3. Hypothyroidism
4. Resolution and return to the
euthyroid state.
Early stages of the disease
– TSH is decreased
– Tg, T3 and T4 are increased due to
the release of pre-formed thyroid
hormone from destroyed follicles.
ESR is >100 mm/h.
Decreased RAIU, even in euthyroid
patients, due to the release of thyroid
hormones from destruction of the
thyroid parenchyma.
Self-limited
Treatment is symptomatic.
– Aspirin and other NSDAIDs for pain
– Steroids if case is severe.
– Short-term thyroid replacement
➔ If needed and may shorten the
duration of symptoms.
– Thyroidectomy
➔ Reserved for the rare patient
who has a prolonged course not
responsive to medical measures
or for recurrent disease.
Painless Thyroiditis
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Autoimmune
May occur sporadically or in the
postpartum period (6 weeks
postpartum).
More common in women 30-60 years.
Physical examination
– Normal sized or minimally enlarged,
slightly firm, non-tender gland.
Laboratory tests are similar to painful
thyroiditis but ESR is normal.
Clinical course parallels painful
thyroiditis.
Symptomatic patients
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– Beta blockers and TH replacement.
Thyroidectomy or RAI ablation
– Rare patient with recurrent, disabling
episodes of thyroiditis.
Chronic (Hashimoto’s) Thyroiditis
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Characteristics
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Antibodies are directed against 3 main
antigens
– Tg (60%)
– TSH-R (60%)
– TPO (95%)
– Less commonly sodium/iodine
symporter (25%)
Associated with medications
– Interferon-alpha
– Lithium
– Amiodarone
Increased incidence in first-degree
relatives of patients with this disease.
Also in patients with Turner’s syndrome
and Down syndrome.
HLA-B8, DR3, and DR5 haplotypes
association. Also alterations in CTLA4,
GITR, STAT3.
Gross
– Gland is mildly enlarged throughout
– Pale, gray-tan cut surface
– Granular, nodular, and firm.
Microscopic
– Diffusely infiltrated by small
lymphocytes and plasma cells.
– Occasionally shows well-developed
germinal centers.
– Follicles are smaller than normal with
reduced amounts of colloid and
increased interstitial tissue.
– Follicles are lined by Hürthle or
Askanazy cells (eosinophilic and
granular cytoplasm)
Clinical Features
More common in women (1:10-20)
between 30-50 years old.
Minimally or moderately enlarged firm
granular gland or the awareness of a
painless anterior neck mass.
– Most common presentation
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20% present with hypothyroidism
5% present with hyperthyroidism
(Hashitoxicosis).
Classic goitrous type
– Diffusely enlarged, firm gland, which
is lobulated.
– Enlarged pyramidal lobe.
Diagnostic Studies
Confirmation
– Elevated TSH
– Presence of thyroid antibodies
FNAB with US
– If with a solitary suspicious nodule or
a rapidly enlarging goiter.
Treatment
TH therapy
– Overly hypothyroid patients.
– Goal is to maintain normal TSH.
Subclinical hypothyroidism
– Normal T4 and elevated TSH
– Management is controversial.
Levothyroxine
– If TSH >10 uIU/mL
– Or if TSH >5-10 uIU/mL with goiter or
anti-TPO.
– Also in middle-aged patients with
CVD risk factors and in pregnant
patients.
Surgery
– Suspicion for malignancy
– For goiters causing compressive
symptoms or cosmetic deformity.
Reidel’s Thyroiditis
Characteristics
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Rare variant of thyroiditis known as
Reidel’s struma or invasive fibrous
thyroiditis.
Replacement of all or part of the thyroid
parenchyma by fibrous tissue.
Associated with
– Other autoimmune diseases
– Focal sclerosing syndromes
Considered a manifestation of IgG4related systemic disease.
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Occurs predominantly in women
between 30-60 years old.
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Clinical Features
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Presents as a painless, hard anterior
neck mass.
Symptoms of hypothyroidism and
hypoparathyroidism may occur.
Physical examination
– Hard, “woody” thyroid gland with
fixation to surrounding tissues.
Diagnosis is confirmed by open thyroid
biopsy because the firm and fibrous
nature of the gland renders FNAB
inadequate.
Treatment
Surgery
– Mainstay of treatment
– Chief goal: decompress the trachea
by wedge excision of the thyroid
isthmus and to make a tissue
diagnosis.
More extensive resections are not
advised.
Thyroid hormone replacement
– For hypothyroid patients.
Corticosteroids and tamoxifen
– For symptomatic patients.
Mycophenolate mofetil and rituximab
– To attenuate the inflammatory
process.
GOITER
Characteristics
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Any enlargement of the gland.
May be diffuse, uninodular, or
multinodular.
Thought to result from TSH stimulation
secondary to inadequate thyroid
hormone synthesis and other paracrine
growth factors.
Clinical Features
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Most are asymptomatic.
Pressure sensation in the neck.
Dyspnea and dysphagia
– When goiters enlarge.
Catarrh – frequent clearing of throats.
Dysphonia from RLN injury
– Rare, except if malignancy is present.
Positive Pemberton’s sign
– Obstruction of venous return at the
thoracic inlet from a substernal
goiter.
– Facial flushing and dilatation of
cervical veins upon raising the arms
above the head.
Acute pain
– From sudden enlargement of nodules
or cysts due to hemorrhage.
Physical examination
– Soft, diffusely enlarged gland (simple
goiter) or nodules of various size and
consistency (multinodular goiter).
– Deviation or compression of the
trachea may be present.
Diagnostic Tests
Euthyroid with normal TSH and lownormal or normal FT4.
Suppressed TSH or hyperthyroid
– If some nodules develop autonomy.
RAIU
– Patchy uptake with hot and cold
areas.
FNAB
– If nodule is dominant or painful or
enlarging.
CT
– To evaluate the extent of retrosternal
extension and airway compression.
Treatment
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Most euthyroid patients with small,
diffuse goiters do not require treatment.
Exogenous thyroid hormone
– For large goiters.
– To reduce TSH stimulation of gland
growth.
– May result in decrease and/or
stabilization of goiter size.
– Most effective for small diffuse
goiters.
Iodine administration
– If goiter is endemic.
Surgical resection (near total or total
thyroidectomy) if goiters
– Continues to increase despite T4
suppression.
– Cause obstructive symptoms.
– Have substernal extension.
– Have malignancy suspected or
proven by FNAB.
– Cosmetically unacceptable.
Lifelong T4 therapy.
Solitary Thyroid Nodule
Characteristics
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History
– Time of onset
– Change in size
– Pain, dysphagia, dyspnea, or choking
– History of hoarseness
➔ RLN injury
– Ask about risk factors.
Pain
– Unusual.
– If present, should raise suspicion for
intrathyroidal hemorrhage in a
benign nodule, thyroiditis, or
malignancy.
Patients with MTC
– Dull, aching sensation.
Physical Examination
Palpate the thyroid gland from behind
the patient and with the neck in mild
extension.
The cricoid cartilage is an important
landmark. The isthmus is below it.
More likely to be malignant
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Hard, gritty nodules or those fixed to
the surrounding structures like the
trachea and strap muscles.
Assess the cervical chain of lymph nodes
and those in the posterior triangle.
Diagnostic Investigations
FNAB
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Single most important test in evaluating
thyroid masses.
Can be performed without US guidance.
With US guidance
– Nodules that are difficult to palpate.
– Cystic or solid nodules that recur
after the initial aspiration.
– Multinodular goiters.
23-gauge needle is used.
If aspirate is bloody
– Reposition the patient in a more
upright position and repeat FNAB
with a finer needle (gauge 25-30).
Laboratory Studies
Most patients with thyroid nodules are
euthyroid.
Determine TSH level.
Hyperthyroid
– 1% risk for malignancy.
Tg level
– Cannot distinguish between benign
or malignant unless it is very high.
– If high, suspect for metastatic thyrid
cancer.
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Helpful in patients who have
undergone total thyroidectomy for
thyroid cancer.
– Also for serial evaluation of patients
undergoing nonoperative
management of thyroid nodules.
Serum calcitonin
– Obtained in patients with MTC or a
family history of MTC or MEN2.
MTC patients
– RET oncogene mutations
– 24hr urine collection for VMA,
metanephrine, and catecholamine
to rule out pheochromocytoma.
Imaging
Ultrasound
– To detect nonpalpable thyroid
nodules.
– To differentiate solid from cystic
nodules.
– To identify adjacent
lymphadenopathy.
Ultrasound can identify fine stippled
calcification and enlarged regional nodes.
Tissue diagnosis is strongly
recommended before thyroidectomy.
CT and MRI
– Unneccessary except for large, fixed,
or substernal lesions.
Thyroid scanning
– Recommended only in patients with
follicular thyroid nodules on FNAB
and a suppressed TSH.
Management
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Thyroidectomy
– Malignant tumors
Aspiration
– Simple thyroid cysts
Unilateral thyroid lobectomy
– If the cyst persists after three
attempts at respiration.
Lobectomy
– Cysts >4cm in diameter.
– Complex cysts with solid and cystic
components.
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If FNAB is used in complex nodules,
sample the solid portion.
If a colloid nodule is diagnosed by FNAB
– Observe patient with serial US and Tg
measurement.
– If nodule enlarges, repeat FNAB.
Levothyroxine
– To maintain TSH between 0.1-1.0
uU/mL
– Controversial.
Thyroidectomy
– If a nodule enlarges on TSH
suppression.
– For cosmetic reasons.
– Exception: patient had previous
irradiation of the gland or has a
family history of thyroid cancer.
– Total or near-total thyroidectomy is
recommended in these patients.
MALIGNANT THYROID DISEASE
Papillary Carcinoma
Characteristics
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80% of all thyroid cancers in iodinesufficient areas.
Predominant thyroid cancer in children
and in individuals exposed to external
radiation.
Occurs more often in women (2:1) 30-40
years.
Most patients are euthyroid.
Slow-growing painless mass in the neck.
Dysphagia, dyspnea, and dysphonia
– Locally advanced invasive disease.
Lymph node metastases
– Common especially in children and
young adults.
– May be the CO.
Lateral aberrant thyroid
– Almost always denotes a cervical
lymph node that has been invaded by
metastatic cancer.
Diagnosis
– FNAB of the thyroid mass or lymph
node.
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Neck US is done next to evaluate the
contralateral lobe for lymph node
metastases in the central and lateral
neck compartments.
Metastases
– Lungs, bone, liver, and brain. (In
order).
Pathology
Gross
– Hard and whitish.
– Remain flat on sectioning.
– Calcifications, necrosis, or cystic
change may be apparent.
Histology
– Papillary projections, a mixed pattern
of papillary and follicular structures,
or a pure follicular pattern.
Diagnosis is established by characteristic
nuclear cellular features.
Orphan Annie nuclei
– Cuboidal cells with pale, abundant
cytoplasm, crowded nuclei that may
demonstrate “grooving,” and
intranuclear cytoplasmic inclusions.
Psammoma bodies.
Variants
– Mixed papillary-follicular tumors
– Follicular variant of papillary thyroid
carcinoma (FVPTC)
➔ Encapsulated
➔ Nonencapsulated (infiltrative)
– Tall cell
– Insular
– Columnar
– Diffuse sclerosing
– Clear cell
– Trabecular
– Poorly differentiated types
– Minimal or occult/microcarcinoma
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Minimal or Occult/Microcarcinoma
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Challenging to diagnose.
Have no invasion.
Diagnosis relies on finding of
characteristic nuclei.
Tumors of 1cm or less in size.
No evidence of local invasiveness.
No lymph node metastases.
Nonpalpable.
Incidental findings.
Better prognosis.
Prognosis
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Encapsulated FVPTC
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Noninvasive follicular thyroid neoplasm
with papillary-like nuclear features
(NIFTP).
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Excellent, >95% 10-year survival rate.
AGES (age, histologic grade,
extrathyroidal invasion)
– Low-risk
➔ Young
➔ Well-differentiated tumors
➔ No metastases
➔ Small primary lesions
– High-risk
➔ Old
➔ Poorly-differentiated tumors
➔ Local invasion
➔ Distant metastases
➔ Large primary lesions.
MACIS
– Postoperative system modified from
AGES.
– Metastases
– Age (40 years)
– Completeness of original surgical
resction
– Extrathyroidal invasion
– Size of original lesion (cm)
AMES
– Age
➔ Men: 5cm)
By DeGroot, et. al.
– Class I: intrathyroidal
– Class II: cervical nodal metastases
– Class III: extrathyroidal invasion
– Class IV: distant metastases
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TNM
– Tumor
– Nodal status
– Metastases
– Minimal extrathyroidal extension is
no longer T3a.
BRAF V600E mutation
– Aggressive tumor characteristic.
– Independent predictor of both tumor
recurrence and mortality.
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Surgical Treatment
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Total or near-total thyroidectomy
– High-risk tumors
– Bilateral tumors
– Tumors >1cm and 4 cm) in older
men are more likely to be malignant.
Genetic Studies
Rule-in
– BRAF
– Ras
– RET/PTC
– PAX/PPARy
– PPV
– NPV
Pathology
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Solitary lesions
Majority are surrounded by a capsule.
Histology
– Follicles are present.
– Lumen may be devoid of colloid.
Malignancy
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Presence of capsular and vascular
invasion.
Minimally invasive tumors
– Grossly encapsulated and have
invasion.
Widely-invasive tumors
– Large vessel invasion and/or broad
areas of capsular invasion.
– May be unencapsulated.
Surgical Treatment
Lobectomy
Total thyroidectomy
– Older patients with follicular lesions
>4cm because of the higher cancer
risk.
– Atypia on FNAB.
– Family history of thyroid cancer
– History of radiation exposure.
– Should be performed when thyroid
cancer is diagnosed.
– Invasive carcinoma or follicular
carcinoma with angioinvasion, with
or withour capsular invasion.
Intraoperative frozen section
– Not really helpful.
– Perfromed if there is capsular or
vascular invasion or when adjancent
lymphadenopathy is present.
Therapeutic neck dissection
– Not needed, but performed if there is
nodal metastases.
Prophylactic neck dissection
– May be performed if tumors are
large.
Prognosis
Mortality rate
– 15% at 10 years
– 30% at 20 years.
Poor long-term prognosis
– Age over 50 years at presentation.
– >4cm tumor size.
– Higher tumor grade.
– Marked vascular invasion.
– Extrathyroidal invasion.
– Distant metastases at the time of
diagnosis.
Hürthle Cell Carcinoma
Characteristics
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3% of all thyroid malignancies.
Subtype of follicular thyroid cancer.
With cascular or capsular invasion and
therefore cannot be diagnosed by FNAB.
Tumors contain sheets of eosinophilic
cells packed with mitochondria
Difference with follicular carcinomas
– This tumor is more often multifocal
and bilateral.
– Do not take up RAI.
– More likely to metastasize to local
nodes and distant sites.
– Associated with a higher mortality
rate.
Management
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Similar to follicular neoplasms.
Lobectomy and isthmusectomy
sufficient.
• Total thyroidectomy
– If found invasive on definitive
paraffin histology.
• Patients should also undergo routine
central neck node removal (similar to
MTC)
• Modified radical neck dissection
– When lateral neck nodes are palpable
or identified by US.
• RAI scanning and ablation
– Usually are ineffective.
– But should be considered to ablate
any residual normal thyroid tissue
and occasionaly ablate tumors
because there is no other good
therapy.
Post-operative Management of Differentiated
Thyroid Cancer
RAI
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Reduces recurrence.
Provides a small improvement in survival.
RAI screening is more sensitive that CXR
or CT for detecting metastases.
It is less sensitive than Tg measurements
for detecting metastatic disease in most
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differentiated thyroid cancers except
Hürthle cell tumors.
Screening and treatment are facilitated
by the removal of all normal thyroid
tissue, which effectively competes for
iodine uptake.
Metastatic differentiated thyroid
carcinoma
– Can be detected and treated by
Iodine 131 in about 75% of patients.
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2015 ATA Guidelines
Macroscopic invasion of tumor into the
perithyroidal soft tissues (gross ETE).
Incomplete tumor resection
Presence of distant metastases (or
postoperative serum thyroglobulin
suggestive of distant metastases.)
Pathologic N1 with any metastatic lymph
node ≥3 cm in largest dimension.
Follicular thyroid cancers with extensive
vascular invasion (>4 foci of vascular
invasion.)
Low-Risk Papillary Thyroid Cancer
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Without local tumor invasion
All macroscopic tumor resected
Absence of aggressive histology
No known distant metastases
No vascular invasion
Clinical N0 or 5 pathologic N1 with all
involved lymph nodes 2–3 cm) or clinically
evident lymph nodes (central,
mediastinal, and lateral neck).
➔ Extranodal extension.
➔ Advancing age.
➔ Lateral neck disease.
– Not for
➔ Papillary microcarcinomas.
➔ Patients with a few (