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THYROID
James Taclin C. Banez, M.D., FPSGS, FPCS
ANATOMY:
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•
•
Location / Parts
Arteries / Venous drainage
Nerve Supply
•
•
•
Sympathetic (cervical ganglion)
Parasympathetis (vagus)
Histology:
Thyroid follicle (thyroglobulin)
• C cells (neuroectoderm – 4th
and 5th ultimo brachial bodies).
•
PHYSIOLOGY:
•
Synthesis & secrets thyroid
hormone (thyroid follicle)
1.
2.
3.
4.
Iodide uptake
Oxidation of iodide to iodine
Organification (thyroxiniodine) MIT / DIT
Coupling of inactive
iodotyrosine T4 /T3
•
•
Stored ----> released by
protease / peptidase
Calcium Level
•
Calcitonin (C cell)
Evaluation of Thyroid Diseases
5.
Clinical history and physical examination
Serum T3 & T4, TSH determination
Thyroid scan
Thyroid ultrasound
CT scan / MRI
6.
FNAC
1.
2.
3.
4.
HYPERTHYROIDISM
(Thyrotoxicosis)
A.
With increase thyroid hormone secretion
1.
2.
3.
B.
Grave’s disease
Toxic nodular goiter
Toxic thyroid adenoma
With out increased thyroid hormone
secretion
1.
2.
3.
Sub-acute thyroiditis
Functioning metastatic thyroid cancer
Struma ovarii
HYPERTHYROIDISM
GRAVE’S Disease (Diffuse Thyroid Goiter)
• Most common form of thyrotoxicosis
• Autoimmune
• Female > male; most prevalent 20-40 y/o
•
Thyroid stimulating antibody
(immunoglobulin)
directed at the TSH receptor or the thyroid
follicular cells.
•
•
LATS (long acting thyroid stimulating antibody)
TRAb (thyroid receptor antibody)
HYPERTHYROIDISM
GRAVE’S Disease (Diffuse Thyroid Goiter)
• Manifestations:
•
Signs/symptoms of thyrotoxicosis:
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heat intolerance
sweating
weight loss, muscle wasting
tachycardia/atrial fibrillation
fine tremors
easy fatigability
hypoactive tendon reflexes
amenorrhea
decrease fertility
easy fatigability, agitation and excitability
diarrhea
HYPERTHYROIDISM
GRAVE’S Disease (Diffuse Thyroid Goiter)
• Triad:
•
•
•
•
diffuse goiter
thyrotoxicosis
exopthalmos
Other:
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hair loss
pretibial myxedema
gynecomastia
splenomegally
HYPERTHYROIDISM
GRAVE’S Disease:
Exopthalmos:
•
Due to increase retro-bulbar tissue:
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Spasm of the upper eyelid,
revealing the sclera above the
corneoscleral limbus
(Dalrymple’s sign)
Lid lag (von graefes sign)
External ophthalmoplegia
(inability to move the eyeball)
Supra and infraorbital swelling
Congestion and edema of the
conjunctiva and sclera (chemosis) ---> ulceration
Progression --> damage of optic
nerve --> decreases visual acuity
and impairment of color vision
(malignant exopthalmos) not corrected
surgically --> blindness
HYPERTHYROIDISM
Diagnosis:
•
Autonomous thyroid function
•
Low TSH
Elevated T3 / T4
Thyroid scan ---> diffuse elevated iodine uptake
•
•
•
Treatment:
•
•
Choices:
1.
2.
3.
•
Antithyroid drugs
Radioactive iodine therapy
Surgery
Choice depends on:
1.
2.
3.
4.
5.
Age
Severity of the disease
Size of the gland
Coexistent pathology (Ophthalmoplegia)
Other factors:
a.
b.
Patient’s preference
Pregnancy
HYPERTHYROIDISM
Antithyroid Drugs:
Propyl thiouracil (PTU)
Methimazole (Tapazole)
Carbimazole
1.
2.
3.
= 100-300mg TID
= 10-20 TID then OD
= 40mg OD
Inhibits the organic binding of iodine and coupling of
iodotyrosine
PTU can also lower conversion of T4 to T3; it can also decrease
thyroid autoantibody levels
Disadvantage of these drugs.
•
•
•
a.
b.
c.
Crosses the placenta --> inhibits fetal thyroid function
Excreted in breast milk
Side effects:
a.
b.
c.
d.
e.
f.
Skin rashes
Fever
Peripheral neuritis
Polyarteritis
Granulocytopenia (reversible)
Agranulocytosis / aplastic anemia (poor prognosis)
HYPERTHYROIDISM
•
Beta blockers (propranolol) – to alleviate
peripheral adrenergic effects
•
Advised medical management
•
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Small diffusely enlarge gland or larger glands that
decreases in size due to antithyroid drugs
Toxic nodule goiters or large diffuse glands or
hyperthyroidism when drug was discontinued --> thyroidectomy / radioactive iodine
HYPERTHYROIDISM
Radioactive Iodine Therapy:
Advantages:
•
•
Avoidance of surgery (no injury to nerve / parathyroid gland)
Reduce cost & ease of treatment
Disadvantages:
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Lifelong thyroxin replacement therapy
Slower correction of hyperthyroidism
Higher relapse rate
Adverse effect of ophthalmopathy
Suitable treatment:
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Small or moderate size goiter
Relapse after medical and surgical therapy
Antithyroid drug and surgery are contraindicated
Contraindicated:
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Pregnant / breast feeding
Ophthalmopathy (progression of eye signs)
Isolated nodular goiter or toxic nodular goiter
Young age (children/adolescence ----> Infertility / carcinoma
HYPERTHYROIDISM
Radioactive Iodine Therapy:
Pt. is placed in euthyroid state with anti-thyroid
drugs. Then discontinue the drugs for 2-3 wks
before RAI tx is started (I 131 sodium iodide)
Complication of RAI tx:
1.
2.
3.
4.
5.
6.
Exacerbations of thyrotoxicosis with arrhythmia
Overt thyroid storm
Hypothyroidism
Risk of fetal damage
Worsening of eye sign
Hyperparathyroidism
HYPERTHYROIDISM
Thyroid Surgery:
Indicated to:
1.
2.
3.
4.
5.
Young patient
With Grave ophthalmopathy
Pregnant
With suspicious thyroid nodule in Grave’s gland
Large nodular toxic goiter w/ low level of radioactive iodine uptake.
Placed patient to euthyroid state prior to thyroid surgery:
1.
2.
3.
Antithyroid drugs
Lugol’s iodine solution (3 drops BID)
Propranolol
Thyroidectomy:
1.
2.
3.
Bilateral subtotal thyroidectomy
Total lobectomy & subtotal lobectomy contra-lateral (Hartley-Dunhill)
Total thyroidectomy
Advantages over RAI:
1.
2.
3.
Immediate cure of the disease
Low incidence of hypothyroidism
Potential removal of coexisting thyroid carcinoma
Disadvantages:
1.
2.
3.
Complication ---> nerve injury (1%) and hypoparathyroidism (13% transient/ 1%
permanent).
Hematoma
Hypertrophic scar formation
HYPERTHYROIDISM
•
Recurrent thyrotoxicosis after surgery---> RAI
Treatment of Exopthalmos:
1.
2.
3.
4.
5.
Tape eyelids at night
Wear eyeglasses
Steroid eye drop / systemic steroid (60mg
prednisone OD) alleviate chemosis.
Lateral tarsorrhaphy to oppose eyelids
Radio-orbital radiation or orbital decompression
HYPERTHYROIDISM
Toxic Nodular Goiter (Plummers’ disease):
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No extrathyroidal manifestation
Milder than Grave’s disease
Treatment:
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Propranolol
Thyroidectomy (lobectomy with isthmectomy)
Toxic adenoma:
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Solitary toxic nodule (Follicular) tumor
Thyrotoxicosis is uncommon unless it is 3 cm in size
or more.
Thyroid storm:
Life threatening
Precipitated by:
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•
1.
2.
Infection (pharyngitis / pneumonitis)
Iodine 131 treatment
Prophylactic treatment: --- Surgery in euthyroid state
Treatment:
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1.
2.
3.
4.
5.
6.
7.
8.
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Fluid replacement
Antithyroid drug
Beta blocker
Lugol’s iodine solution
Hydrocortisone
Cooling blanket
Sedation
Extreme cases ----> peritoneal dialysis or hemofiltration to lowe T4&T3
Avoid ASPIRIN ---> increases free thyroid hormone levels
HYPOTHYROIDISM
Causes:
Primary:
A.
Autoimmune thyroiditis
1.
Hashimotos thyroiditis
Primary myxedema
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Iatrogenic
2.
Thyroidectomy
Iodine 131 tx
Antithyroid drugs
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Congenital (Cretinism)
3.
Thyroid dysgenesis
Dyshormonogenesis
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Inflammatory
4.
Subacute thyroiditis
Riedels thyroiditis
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Metabolism
5.
Iodine deficiency
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Secondary:
B.
1.
2.
3.
Hypopituitarism
Hypothalamic hypothyroidism
Peripheral resistance to thyroid hormone
Treatment:
L-thyroxine (50-100ug)
THYROIDITIS
Acute Suppurative Thyroiditis
A.
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Uncommon
Associated with URTI
Staphylococcuc, Streptococcus and Pneumococci
E. Coli
Sx: - acute thyroid pain
- dysphagia
- fever
Dx: - FNA ----> smear and CS
Tx: - IV antibiotics / drain (abscess)
THYROIDITIS
Nonsuppurative Thyroiditis:
B.
Hashimotos disease (Autoimmune lymphocytic thyroiditis)
1.
•
•
Most common form of chronic lymphocytic thyroiditis
Autoimmune disease:
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Antithyroglobulin / antimicrosomal antibodies
10 x more in females; 30 – 60y/o
Familial; 50% in first degree relatives
Predisposing factors:
1.
2.
3.
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Down syndrome
Familial Alzheimer’s disease
Turner syndrome
Can co-exist with papillary CA
S/Sx: - Tightness in the throat (most common)
- Painless, nontender enlargement of gland
Dx: - Increase TSH, decrease T3 & T4
- (+) Anti-thyroid antibodies
- FNA ---> rule out CA (confirmatory)
Tx: - Medical if w/o compression ---->
thyroid hormone
- Surgical:
1. Obstructive
2. Cosmetically unacceptable
3. Thyroid carcinoma coexist
THYROIDITIS
B.
Nonsuppurative Thyroiditis:
Subacute Thyroiditis (De Quervans
Thyroiditis / Giant Cell Thyroiditis)
2.
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Exact cause unknown
Female 5x more the males
20 – 40 y/o
S/Sx:
- Tender enlargement of the gland
- Fever, malaise w/ unilateral or bilateral
thyroid pain
Dx:
- FNA
- ESR (increase)
- Neutrophilia
Tx:
- NSAIDS
- Prednisone
THYROIDITIS
B.
Nonsuppurative Thyroiditis:
Riedels’ Thyroiditis:
3.
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Marked dense invasive fibrosis that may involve surrounding structures
Can cause hypoparathyroidism
Unknown cause ( maybe part of fibrosclerosis – retroperitoneum,
mediastinum, lacrimal gland and bile duct)
S/Sx: - Compression symptoms
- Hoarseness
- dyspnea
- stridor
- dysphagia
Tx: - Tamoxifen
- Steroid
- Isthmectomy – to relieve
compression symptom
- Thyroxine replacement
GOITER
•
Enlargement of the thyroid gland in a
euthyroid pt not associated with neoplasm or
inflammation:
Familial:
1.
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Inherited enzymatic defect (dyshormonogenesis)
Autosomal recessive
Hypothyroidism / euthyroid
Endemic:
2.
•
Iodine deficiency
Sporadic:
3.
•
No definite cause, excludes goiter caused by thyroiditis
and neoplasm as well as endemic goiter
GOITER
Pathology:
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May be diffusely enlarged
and smooth, or enlarged
markedly nodular
Nodules are filled w/
gelatinous, colloid rich
material and scattered
between areas of normal
thyroid tissues
With areas of
degeneration, hemorrhage
and calcification.
GOITER
S/Sx:
•
Asymptomatic usually
•
Pressure symptoms usually
1.
2.
3.
4.
5.
Dysphagia
Dyspnea
Paralysis of recurrent laryngeal
nerve
Sudden pain associated with rapid
enlargement of the gland --->
hemorrhage into a colloid nodule
or cyst
Superior mesenteric syndrome
due retro-sternal extension
causing facial flushing that is
accentuated by raising his arm
above the head (Pemberton’s
sign).
GOITER
Dx:
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FNAC ---> specially if one nodule predominates, or painful
or has recently enlarged. To rule out CA
TSH, T3 & T4 ---> usually normal
---> pts > 60y/o w/ long standing
multinodular goiters (>17yrs) develops thyrotoxicosis
(Plummer’s dse). Low TSH w/ increased T3 but normal T4
(T3 toxicosis)
Tx:
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•
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No tx for euthyroid, small, diffuse goiter
Thyroxine ---> for large diffuse goiter; to depress TSH
stimulation and reduce hyperplasia
Iodine ---> for endemic goiter
Surgery:
1.
2.
3.
Cosmetically acceptable
Compression symptoms
Suspicion for malignancy
Solitary or Dominant Thyroid Nodule
Most are benign (colloid nodule/adenomas)
Physician should:
•
1.
2.
3.
Perform an accurate clinical assessment
Appreciate the risk factors for thyroid carcinoma
Which pts would benefit from surgery
Risk factors for thyroid CA:
1.
2.
3.
4.
Low-dose radiation to head & neck (<2000 rad)
- >2000rads causes destruction of thyroid gld.
- tends to be papillary type, multi-focal w/ higher incidence of LN metastases.
Family hx of thyroid CA
- Medullary CA – inherited as an autosomal dominanat trait
- Papillary CA – 6% familial dse.
Age
- thyroid nodule in children and elderly are more likely to be malignant.
Signs
a.
b.
c.
d.
e.
Rapid enlargement of an old or new nodule
Symptoms of local invasion or compression symptoms
Consistency: Hard, gritty or fixed to surrounding structures
Palpable cervical lymphadenopathy
A cyst larger than 4 cm in diameter or in ultrasound is complex has 15% incidence of
malignancy
Solitary or Dominant Thyroid Nodule
Work up for Thyroid nodule:
1.
FNAC – procedure of choice
benign
65%
malignant 5%
Suspicious 15%
Non-diagnostic
15%
•
Limitation of FNAC:
1.
2.
•
false (+) - 1%
false (-) - 5%
Follicular or Hurtle cell neoplasm (needs vascular and capsular invasion)
Hx of head and neck radiation and family hx of thyroid CA usually has
multifocal lesions.
If FNAC encountered a cyst ---> drain completely 75% is
curative; if cyst persist after 3 attempts ---> unilateral lobectomy
Solitary or Dominant Thyroid Nodule
Work up for Thyroid nodule:
Thyroid ultrasonography:
2.
•
Use to a) follow up the size of suspected benign
nodules diagnosed by FNAC
b) to detect presence of non-palpable
nodules to locate and differentiate it
for cyst or solid
MRI / CT scan:
3.
•
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For large retro-sternal extension
For recurrent or persistent thyroid tumor and to
differentiate recurrence from postoperative fibrosis
Detect the presence of invasion, sign of CA.
Solitary or Dominant Thyroid Nodule
Work up for Thyroid nodule:
4.
Thyroid isotope imaging:
Check the function and locate small lesions
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Cold -----------> 10 – 25% malignant
Hot -----------> 1% malignant
Laboratory:
5.
Thyroid function test:
a.
•
Serum thyroglobulin level:
b.
•
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To detect presence of metastatic lesions
Check completion of thyroidectomy
Not used in medullary and anaplastic thyroid CA
Serum calcitonin:
c.
•
d.
Not useful in assessing thyroid nodule
Follow up in medullary CA
RET oncogens (+) pt should have 24 hrs urine determination of VMA,
metanephrine and cathecolamine to rule out a coexisting
pheochromocytoma (for medullary CA)
Solitary or Dominant Thyroid Nodule
Approach for Thyroid Nodule
MALIGNANT THYROID
•
90 – 95% are differentiated tumor w/
follicular origin
1.
2.
3.
•
6% arise from parafollicular cells:
1.
•
Papillary thyroid adenocarcinoma
Follicular adenocarcinoma
Hurtle cell carcinoma
Medullary carcinoma of thyroid
1% poorly differentiated
1.
Anaplastic thyroid carcinoma
MALIGNANT THYROID
Oncogene associated w/ Thyroid carcinoma:
RET oncogene:
1.
•
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Seen in papillary and medullary thyroid CA
Located in chromosome 10
TRK – A:
2.
•
Chromosome 1
Mutated ras oncogenes:
3.
•
Follicular thyroid carcinoma, thyroid adenoma and
multinodular goiter
Mutated p53 gene:
4.
•
Anaplastic thyroid carcinoma
MALIGNANT THYROID
Papillary Thyroid Carcinoma:
•
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Most common (80%)
Predominant thyroid CA in children (75%)
Usually due to radiation exposure of the neck (85-90%)
Multi-focal (30-88%); has LN spread (para-tracheal & cervical LN).
Can invade trachea, esophagus and recurrent laryngeal nerve; late
hematogenous spread.
Mixed tumor (papillary & follicular): variant of papillary CA, but
classified as papillary for it biologically acts as papillary CA.
Orphan Annie Nuclei:
•
•
Characteristic cellular feature
Abundant cytoplasm, crowded nuclei
and intra-nuclear cytoplasmic inclusion
MALIGNANT THYROID
Papillary Thyroid Carcinoma:
3 forms of papillary CA (based on size and extent):
Minimal or occult / micro carcinoma
1.
•
•
•
•
Intra-thyroidal Tumors:
2.
•
•
> 1cm and confined to the thyroid gland
(-) extra thyroidal invasion
Extra-thyroidal Tumors:
3.
•
•
1 cm or less, no capsular invasion
Non-palpable and usually an incidental finding intra-op or
autopsy
Recurrence rate ----> 7%
Mortality ------------> 0.5%
Locally advanced with invasion through the thyroid capsule
into adjacent structures.
All types can be associated w/ LN metastases and intrathyroidal blood vessel invasion or occasionally metastases
MALIGNANT THYROID
Papillary Thyroid Carcinoma:
S/Sx:
•
•
Euthyroid, slow growing painless mass
Signs of local invasions:
•
•
•
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Dysphagia
Dyspnea
Hoarseness of voice
Palpable cervical LN more apparent than primary lesion
(lateral aberrant thyroid)
Uncommon distant metastases (lung metastases in children)
Diagnosis:
•
•
FNAC (specific and sensitive for papillary, medullary and
anaplastic)
CT/MRI in pts w/ extensive local or sub-sternal extension
MALIGNANT THYROID
Papillary Thyroid Carcinoma:
Prognostic indicators: (85% 10yrs survival)
4.
AGES scale:
A- age G- grade
E- extent
S- size
MACIS scale:
M- metastases
A- age
C- completeness of resection
I- extra thyroidal invasion
S- size
AMES
TNM
•
Distant metastases (bone): most significant
1.
2.
3.
prognostic indicator overall
MALIGNANT THYROID
Papillary Thyroid Carcinoma: (SURGERY)
•
Lobectomy with isthmectomy acceptable for minimal
papillary thyroid CA
•
Total thyroidectomy (near total) if:
1.
2.
3.
4.
•
female > 50y/o
Thyroidectomy w/ modified radical neck dissection:
•
•
•
Size: if tumor > 3cm
Age:
male > 40y/o
Angioinvasion
Distant metastases
If with clinically palpable cervical lymphadenopathy
Not done for prophylaxis
Reasons for total thyroidectomy:
1.
2.
3.
4.
85% is multifocal
To decrease incidence of anaplasia in any residual tissue
Facilitate the diagnosis of unsuspected metastatic disease by RAI scanning
or treatment
Greater sensitivity of blood thyroglobulin level to predict recurrent or
persistent of the disease.
MALIGNANT THYROID
Follicular Thyroid Carcinoma:
10%; Female > Male (3:1), mean age= 50y/o
More frequent in Iodine deficiency area
Vascular invasion & hematogenous spread is more common (bone, lung and
liver).
Types:
•
•
•
•
Minimally invasive tumor:
1.
Invasion into but not through the tumor capsule
Previously called atypical adenoma
•
•
Invasive tumors (capsular/vascular)
2.
•
•
1% thyrotoxic
Dx / Tx:
•
•
Prognosis:
1.
2.
3.
4.
5.
6.
•
FNAC not helpful ----> lobectomy and isthmectomy (frozen section) ----> (+) total
thyroidectomy ----> iodine 131 to detect distant metastases and for ablation.
Age over 50y/o
> 4cm size
Higher tumor grade
Marked vascular invasion
Marked extra-thyroidal invasion
Distant metastasis
Mortality: 40 % ----> 10 yrs
MALIGNANT THYROID
HURTLE CELL THYROID TUMOR:
3 – 5%, intermediate, uni-focal
• Male : Female (2:1), spread by lymphatics
• Derived from oxyphilic cells of the thyroid gld.
• Possess TSH receptors and produces thyroglobulin
• Only 10% takes up iodine hence thallium scan is used to
localize distant metastasis
• Often multifocal and bilateral
Dx:
FNAC ----> 20% malignant
Tx:
- total thyroidectomy for RAI ablation usually fails
- mod radical neck dissection if with palpable
cervical LN
- Thyroid suppression is suggested
Prognosis: 60% ------> 5yr survival
•
MALIGNANT THYROID
MEDULLARY THYROID CARCINOMA:
•
•
•
•
5-7%; Aggressive tumor; 50-60y/o
Arise from parafollicular or C cells of the thyroid
(neuroectodermal-ultimobrachial bodies 4th &5th branchial pouches.
Secrets calcitonin (95%); 85% secrets carcinoembryonic antigen
(CEA)
Sporadic 90%
•
•
•
unifocal, usually 45y/o
worse prognosis
Familial 10%
•
Associated with:
•
•
•
•
MEN IIA or Sipples’ syndrome (MTC, hyperplastic parathyroid and
pheochromocytoma
MEN IIB (MTC, pheochromocytoma, ganglioneuromatosis and Marfan,s syndrome)
Multifocal, usually 35 y/o
Better prognosis
MALIGNANT THYROID
MEDULLARY THYROID CARCINOMA:
•
•
Does not concentrate Iodine 131, Thallium scan is used to
localized distal metastasis.
Spread:
•
•
•
•
Lymphatics (neck and superior mediastinum)
Blood ---> liver, bone (osteoblastic) and lung
Local invasion
Can secrets:
•
Calcitonin
Histamine
Serotinin (causes diarrhea)
ACTH 2-4% causing Cushing syndrome
CEA
Prostaglandin E2 and F2 alpha
•
Hx ‘ PE; serum calcitonin, CEA, FNAC, Serum calcium
•
•
•
•
•
Dx:
MALIGNANT THYROID
Tx:
•
Total thyroidectomy
•
•
MRND is done for:
•
•
•
•
•
2.
Palpable cervical LN
>2cm tumor for 60% nodal metastasis
Tumor debulking in cases of metastatic and local recurrence should be
done to ameliorate symptoms of flushing and diarrhea and help to
decrease the risk of death.
All pt should be screen for pheochromocytoma (MEN II) w/c shoud be
resected first.
Selective removal of the parathyroid shd be done if preoperatively has
hypercalcemia.
Follow up:
Prognosis:
1.
Radiotherapy and chemotherapy ---> failure
- serum calcium / CEA level
Localize -------> 80% 10 year survival
(+) LN --------> 45% 10 year survival
Best ------------> Worst prognosis
Familial non-MEN MTC -----> MEN IIA ----> Sporadic cases ------> MEN IIB
MALIGNANT THYROID
Anaplastic Thyroid Carcinoma:
•
•
•
•
1 – 3% most aggressive, few survive > 6 months
Most arise from previous differentiated thyroid CA
Low incident could be due to low iodine deficiency
70 – 80 y/o
Treatment:
•
Radiotherapy ----> doxorubicin ----> debulking
thyroidectomy ----> completion with radiotherapy and
chemotherapy
MALIGNANT THYROID
LYMPHOMA:
•
•
•
•
1 – 5% non-Hodgkin B cell
Usually develops in pts w/ chronic lymphocytic thyroiditis (Hashimotos
thyroiditis)
S/Sx similar with anaplastic CA, compression symptoms is the most
common
Tx: Chemotherapy
Cyclophosphamide
• Doxorubicin
• Vincristine
• Prednison
Radiotherapy
Surgery: - done for diagnosis and to alleviate compression
symptoms
•
•
80% survival if confined to the gland; 40% it had spread
Metastatic Carcinoma:
•
Rare; hypernephroma is the most common primary site
Thank you