Thyroid Disease

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 Embryology

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 Thyro-glossal cyst

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Anatomy

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 Thyroid Physiology
Synthesis of the thyroid hormone
Trapping of inorganic iodide from the blood:
Oxidation of iodide to iodine.
Binding of iodine with tyrosine to form iodotyrosines.
Coupling of mono-iodotyrosines and di-iodotyrosine to
form T3, T4

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 Synthesis of the thyroid hormone
TSH
unbound T4 and T3.

T3 is the more important and is also produced in the

periphery by conversion from T4.
T3 is quick acting (within a few hours) whereasT4
acts more slowly (4-14 days)

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 Effects of Thyroid Hormone
Fetal brain and skeletal maturation
Increase in basal metabolic rate
Increases sensitivity to catecholamines
Stimulates gut motility
Increase bone turnover
Increase in serum glucose, decrease in serum
cholesterol

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 Thyroid Evaluation
 TRH
 TSH
 Total T3, T4
 Free T3, T4
 RAIU
 Thyroglobulin
 Antibodies: Anti-TPO, Anti-TSHr

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 Common Thyroid Disorders

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 Diffuse Toxic Goiter
Graves’ Disease
Most common cause of thyrotoxicosis
Autoimmune condition with anti-TSH antibodies
female preponderance (5:1),
 peak incidence between the ages of 40 to 60
years.
Onset of disease may be related to severe stress
which alters the immune response

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 Etiology, Pathogenesis, and Pathology

The exact etiology of the initiation of

the autoimmune process in Graves'
disease is not known.

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 Pathology
 Macroscopically,

Microscopically,

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 Clinical Features
 Hyperthyroid symptoms
 heat intolerance,
 increased sweating and thirst,
 weight loss despite adequate caloric intake
 . Symptoms of increased adrenergic stimulation
 palpitations, nervousness, fatigue, emotional lability,
hyperkinesis, and tremors.
 GI symptoms .
 Female patients often develop amenorrhea, decreased fertility,
and an increased incidence of miscarriages.
 Children experience rapid growth with early bone maturation,
older patients may present with cardiovascular complications
such as atrial fibrillation and congestive heart failure.

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 physical examination
weight loss
facial flushing
. The skin is warm and moist and Tachycardia or atrial
fibrillation is present with cutaneous vasodilation
leading to a widening of the pulse pressure and a rapid
falloff in the transmitted pulse wave (collapsing pulse).
 A fine tremor,
muscle wasting, and proximal muscle group weakness
with hyperactive tendon reflexes often are present.

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 Eye symptoms
lid lag (von Graefe's sign)
spasm of the upper eyelid revealing the sclera above the
corneoscleral limbus (Dalrymple's sign),
prominent stare, due to catecholamine excess. In
periorbital edema
conjunctival swelling and congestion(chemosis),
proptosis, limitation of upward and lateral gaze (from
involvement of the inferior and medial rectus muscles,
respectively),
keratitis,
blindness due to optic nerve involvement.

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 Graves’ Ophthalmopathy

Class one: spasm of

upper lids with
thyrotoxicosis
Class two: periorbital
edema and chemosis
Class three: proptosis
Class four: extraocular
muscle involvement
Class five: corneal
involvement
Class six: loss of vision
due to optic nerve
involvement

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 Diagnostic Tests
suppressed TSH
123I uptake and scan
Anti-Tg and anti-TPO antibodies are elevated in up
to 75% of patients, but are not specific.
Elevated TSH-R or thyroid-stimulating antibodies
(TSAb) are diagnostic of Graves' disease and are
increased in about 90% of patients
MRI scans of the orbits are useful in evaluating
Graves' ophthalmopathy.

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 Treatment
Medical treatment

Propylthiouracil, methimazole
PTU is preferred in pregnant and breastfeeding women
high relapse rate when these drugs are discontinued
(a) small, nontoxic goiters less than 40 g,
(b) mildly elevated thyroid hormone levels, and
 (c) rapid decrease in gland size with antithyroid
medications.

beta-blocking agents

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 Radioactive Iodine Therapy (131I)
older patients with small or moderate-sized goiters,
relapsed after medical or surgical therapy
those in whom antithyroid drugs or surgery are
contraindicated.
Absolute contraindications to RAI
women who are pregnant or breastfeeding. Relative
contraindications
 young patients (i.e., especially children and
adolescents), those with thyroid nodules, and those
with ophthalmopathy.

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 Surgical Treatment
surgery is recommended when RAI is contraindicated as in
patients who
 (a) have confirmed cancer or suspicious thyroid nodules,
 (b) are young
 (c) are pregnant or desire to conceive soon after treatment,
(d) have had severe reactions to antithyroid medications,
(e) have large goiters causing compressive symptoms, and
 (f) are reluctant to undergo RAI therapy.

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 Toxic Multinodular Goiter
occur in older individuals
thyroid nodules become autonomous to cause
hyperthyroidism.
Symptoms and signs of hyperthyroidism are similar to
Graves' disease, but extrathyroidal manifestations are
absent.
Diagnostic Studies
similar to Graves' disease
Treatment
Surgical resection is the preferred treatment

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 Toxic Adenoma
(Plummer's Disease)
Hyperthyroidism from a single hyperfunctioning nodule
Physical examination usually reveals a solitary thyroid
nodule without palpable thyroid tissue on the
contralateral side
RAI scanning shows a "hot" nodule with suppression
the rest of the thyroid gland.
Surgery (lobectomy and isthmusectomy) is preferred to
treat young patients and those with larger nodules.

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 Hypothyroidism
 Primary (Increased TSH Levels) Secondary (Decreased
TSH Levels)

Pituitary tumor
Hashimoto's thyroiditis Pituitary resection or
ablation
RAI therapy for Graves' disease
Postthyroidectomy
Tertiary
Excessive iodine intake
Subacute thyroiditis Hypothalamic
insufficiency
Medications: antithyroid drugs,
Resistance to thyroid
lithium hormone
Rare: iodine deficiency,
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 Clinical Features
In childhood
Failure to thrive and severe mental retardation
abdominal distention, umbilical hernia, and rectal
prolapse.
In adult
tiredness, weight gain, cold intolerance, constipation,
and menorrhagia.

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 Skin
rough and dry and often develops a yellowish hue
Hair becomes dry and brittle
loss of the outer two thirds of the eyebrows
enlarged tongue
Libido and fertility are impaired
bradycardia, cardiomegaly, pericardial effusion,
reduced cardiac output, and pulmonary effusions

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 Hypothyroidism
 Diagnosis
 Low FT4, High TSH (Primary, check for antibodies)
 Low FT4, Low TSH (Secondary or Tertiary, TRH
stimulation test, MRI)
 Treatment
 Levothyroxine (T ) due to longer half life
4
 Treatment prevents bone loss, cardiomyopathy,
myxedema

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Thyroiditi
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s
 Hashimoto’s
(Chronic, Lymphocytic)
 Most common cause of hypothyroidism
 Result of antibodies to TPO, TBG
 Commonly presents in females 30-50 yrs.
 Usually non-tender and asymptomatic
 Lab values
 High TSH
 Low T4
 Anti-TPO Ab
 Anti-TBG Ab
 Treat with Levothyroxine

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 Subacute Thyroiditis
DeQuervain’s, Granulomatous

Most common cause of painful thyroiditis

Often follows a URI
FNA may reveal multinucleated giant cells or
granulomatous change.
Course
Pain and thyrotoxicosis (3-6 weeks)
Asymptomatic euthyroidism
Hypothyroid period (weeks to months)
Recovery (complete in 95% after 4-6 months)

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 Subacute Thyroiditis
DeQuervain’s, Granulomatous
 Diagnosis
 Elevated ESR
 Anemia (normochromic, normocytic)
 Low TSH, Elevated T4 > T3, Low anti-TPO/Tgb
 Low RAI uptake (same as silent thyroiditis)

 Treatment
 NSAID’s and salicylates.
 Oral steroids in severe cases
 Beta blockers for symptoms of hyperthyroidism,
 Symptoms can recur requiring repeat treatment
 Graves’ disease may occasionally develop as a late sequellae

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 Acute Thyroiditis
 Causes
 68% Bacterial (S. aureus, S. pyogenes)
 15% Fungal
 9% Mycobacterial

 May occur secondary to

 Pharyngeal space infections
 Persistent Thyroglossal remnants
 Thyroid surgery wound infections (rare)

 More common in HIV

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 Acute Thyroiditis
 Diagnosis
 Warm, tender, enlarged thyroid
 FNA to drain abscess, obtain culture
 RAIU normal (versus decreased in DeQuervain’s)
 CT or US if infected TGDC suspected

 Treatment
 High mortality without prompt treatment
 IV Antibiotics
 Nafcillin / Gentamycin or Rocephin for empiric therapy
 Recovery is usually complete

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 Riedel’s Thyroiditis
 Rare disease involving fibrosis of the thyroid gland

 Diagnosis
 Thyroid antibodies are present in 2/3
 Painless goiter “woody”
 Open biopsy often needed to diagnose
 Associated with focal sclerosis syndromes (retroperitoneal,
mediastinal, retroorbital, and sclerosing cholangitis)

 Treatment
 Resection for compressive symptoms
 Chemotherapy with Tamoxifen, Methotrexate, or steroids may be
effective
 Thyroid hormone only for symptoms of hypothyroidism

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 Goiter
 Goiter: Chronic enlargement
of the thyroid gland not due
to neoplasm
 Endemic goiter
 Common in China and central
Africa
 Sporadic goiter
 Multinodular goiter in
sporadic areas often denotes
the presence of multiple
nodules rather than gross gland
enlargement
 Familial
 TSH stimulation secondary
to inadequate thyroid
hormone synthesis and other
paracrine growth

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 Goiter
 Etiology
 Hashimoto’s thyroiditis
 Early stages only, late stages show atrophic changes
 May present with hypo, hyper, or euthyroid states
 Graves’ disease
 Due to chronic stimulation of TSH receptor
 Diet
 Brassica (cabbage, turnips, cauliflower, broccoli)
 Chronic Iodine excess
 Iodine excess leads to increased colloid formation and can
prevent hormone release
 If a patient does not develop iodine leak, excess iodine can
lead to goiter
 Medications
 Lithium prevents release of hormone, causes goiter in 6% of
chronic users
 Neoplasm

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 Goiter
Clinical Features
 nontoxic goiters are asymptomatic
 compressive symptoms such as dyspnea and dysphagia
 Obstruction of venous return at the thoracic inlet from a
substernal goiter
Diagnostic Tests
 normal TSH and low-normal or normal-free T levels
4
 RAI uptake often shows patchy uptake with areas of hot
and cold nodules.
 RAI uptake often shows patchy uptake with areas of hot
and cold nodules.
 CT scans

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 Treatment
Most euthyroid patients with small, diffuse goiters do
not require treatment.
large goiters exogenous thyroid hormone to reduce the
TSH stimulation of gland growth
Surgical resection

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 Thyroid Nodules
Lifetime risk of palpable nodule 5-10%
50% of the population has a nodule on autopsy or
ultrasound
Only 1 in 20 is malignant

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 THYROID MALIGNANCY

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 Introduction
Infrequent cancer -1% of all cancers
Most common endocrine malignancy (90%)
1200 pts die annually
Requires multidisciplinary approach
High survival rates
Women 3 times more than men.
Peak incidence 30-40s.
Papillary 80%, follicular 10%, medullary 5-10%,
anaplastic 1-2%.

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 Etiology/Risk Factors
 Arise from the two cell types in the gland.
 Radiation exposure (papillary).
 Populations with low dietary iodine have a higher
proportion of follicular and anaplastic cancers.
 Solitary thyroid nodules in patients >60 or <30 years of age
 Symptoms of pain or pressure (especially a change in
voice)
 Male sex
 Large Nodules (>3 or 4 cm)
 Growth of nodule

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 Papillary Carcinoma
 Most common (80%)
 Women 3 times more common
 30-40 years of age
 Familial also (FAP)
 Radiation exposure as a child
 Patients with Hashimoto’s thyroiditis
 Slow growing, TSH sensitive, take up iodine, TSH
stimulation produces thryroglobulin response

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 Papillary Carcinoma
Pathology:Unencapsulated, papillary prjection. Well
differentiated, rare mitoses.
50% have psammoma bodies (calcification)
Multicentric with tumor present in contralateral lobe as
well.

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 Papillary Carcinoma
Local invasion through capsule, invading trachea,
nerve, causing dyspnea, hoarseness.
Propensity to spread to the cervical lymph nodes.
Clinically evident in 1/3 patients. Most commonly
central compartment, located medial to carotids, from
hyoid to sternal notch.
Distant spread to bone, lungs.

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 Follicular Carcinoma
Second most common (10%)
Iodine deficient areas
3 times more in women
Present more advanced in stage than papillary
Late 40’s
Also TSH sensitive, takes up iodine, produces
thryroglobulin.

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 Follicular Carcinoma
Pathology: round, encapsulated, cystic changes,
fibrosis, hemorrhages. Microscopically, neoplastic
follicular cells.
Differentiated from follicular adenomas by the
presence of capsule invasion,vascular invasion.
Cannot be diagnosed based on FNA

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 Follicular Carcinoma
Local invasion is similar to papillary cancer with the
same presentation.
Cervical metastases are uncommon.
Distant metastases is significantly higher (20%), with
lung and bone most common sites.

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 Treatment and Prognosis

Surgical excision whenever possible .

Total thyroidectomy has been mainstay (all apparent

thyroid tissue removed). Complications include nerve
damage bilaterally, parathyroid injury bilaterally.
After, get radioiodine scan, ablation if residual disease
or recurrence

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 Over the years, modification to procedure to reduce
the above complications.
Subtotal thyroidectomy( small portion of thyroid
tissue opposite the side of malignancy is left in place)
and postop ablation.
Thyroid lobectomy and isthmectomy also a viable
option with small tumors

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 Postoperative Radioiodine and Ablation
Radioiodine targets residual thyroid tissue and tumor
after thyroidectomy.
Given in diagnostic doses and therapeutic doses to
ablate tissue.

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 Thyroid Suppression Therapy
 Maintained on thyroxine after surgery and ablation.
Low TSH levels reduce tumor growth rates and
reduce recurrence rates.
 Follow-up q 6 months with thyroglobulin levels and
repeat scans.
 Thyroglobulin is good because well differentiated
tumors produce it.

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 Prognosis
 AGES

 Age: at diagnosis. Cancer relate death more common

if patient is older than 40 years.
 Recurrences common in patients diagnosed when
they were less than 20 years or older than 60 years.
 Men are twice more likely as women to die.
 Tumors greater than 4 cm have higher recurrence,
death.
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 Hurthle Cell
 A variant of follicular, also known as oncocytic
carcinoma.
 5 year survival 50%.
 More common in women than men, presents in 5th
decade of life.
 Same clinical presentation.
 Cannot diagnose on FNA
 Does not take up iodine, so treat aggressively.
 Thyroid suppression and radioiodine don’t work.

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 Medullary Carcinoma
5%, female> male
75% sporadically, 25% familial.
Familial cases are usually all over the gland, sporadic
usually not multifocal.
MEN 2A, MEN2B and FMTC syndromes

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 Men 2a, 2b, FMTC
 MEN 2a is Sipple syndrome,MTC,
pheochromocytoma, hyperparathyroidism.
 MEN 2b is MTC, pheo, ganglionomas, marfan
habitus.
 FMTC is just MTC
 Medullary cancer in these are most aggressive,
younger age, rapid growth and metastases.

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 Treatment
 Total thyroidectomy
 Lymph node dissection of level VI.
 Parathyroid reimplantation if necessary.
 Lymph node mets are very common.
 Prophylactic thyroidectomy in children with MEN
2a,b.
 Surveillance with CEA, calcitonin.
 Does not take up iodine, so no radioiodine.
 Prognosis 10 y is 65%.

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 Anaplastic Thyroid Carcinoma
 Extremely aggressive and exceptionally virulent
 Composed wholly or in part of undifferentiated cells
 Tumor is typically hard, poorly circumscribed, and
fixed to surrounding structures
 Often occurs in the elderly population (mean age: 65
years)
 3-fold greater risk in iodine-deficient areas

Primary Thyroid Lymphoma

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 Treatment
Thyroid surgery
Advantage of near-total thyroidectomy :
can be ablated with RAI
can be followed with thyroglobulin levels

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 Follow up
whole-body scan is negative and Tg level are low →
repeat scan perform one year later→still negative
→management with suppressive therapy and
measurements of Tg every 6 to 12 months
Scan negative, Tg-positive(>5 to 10 ng/mL)
→radioiodine treatment.
Lung metastasis:CXR,131I scan,spiral CT
Bone metastasis:bone scintigraphy , CT , MRI

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 Indications for Thyroid Lobectomy
Suspicion for malignancy
Compressive symptoms
Cosmetic issues
Well-differentiated thyroid carcinoma in low risk
patient (controversial)

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 Indications for Total Thyroidectomy
Well-differentiated thyroid cancer
Medullary thyroid cancer
Sarcoma of thyroid
Lymphoma of thyroid
Obstructive goiter

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 Thyroid follicular cells arise primarily from:
a the laryngeal cartilage
b the second bronchial arch
c the oesophagus
d the base of the tongue

the parafollicular (C) cells that arise from the 4th

pharyngeal pouch.

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 FNAC can reliably diagnose all types of thyroid
cancer except:
a follicular thyroid cancer
b papillary thyroid cancer
c anaplastic thyroid cancer
d medullary thyroid cancer

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 The type of thyroid cancer with the worst prognosis
(5-year survival <1%) is:
a papillary thyroid cancer
b follicular thyroid cancer
c anaplastic thyroid cancer
d medullary thyroid cancer

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 Thyroiditis presenting following a viral infection with
an exquisitely tender, enlarged, firm thyroid gland,
and with systemic symptoms of headache and
malaise is generally due to:
a Hashimoto’s thyroiditis
b de Quervain’s (subacute) thyroiditis
c Reidels thyroiditis
d acute bacterial thyroiditis

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 Damage to one recurrent laryngeal nerve during
thyroidectomy generally leads to:
a the need for a tracheostomy
b an inability to sing high notes
c inability to project the voice to the back of a hall
d a hoarse voice

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