Download Thyroid Nodules

In
The
Name
Of
God
Thyroid Nodules
(Epidemiology;Etiology &Pathogenesis)
Nodule definition
A discrete lesion within the
thyroid gland
that is due to an abnormal focal
growth of thyroid cells.
-Benign
-Malignant
(Hyper;Hypo Or Normo- function)
Factors associated with thyroid nodules
• Iodine deficiency
• Genetics:
-Family clustering
-Monozygotes
-Sex differences(F>M)
-Mutations(Tg;NIS;Tpo;TSH-R;Pendrin)
-Chromosoms(14q;Xp22;3q26)
• Environmental:
-Cigarette smoking
-Infections
-Drugs
-Goiterogens
Thyroid Nodules:
Differential Diagnosis
•
Subacute Thyroiditis
•Metastasis
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Prior thyroid surgery
•Lymphadenopathy
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Thyroid hemiagenesis
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Cystic hygroma
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Aneurysm
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Bronchocele
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Laryngocele
•Thyroglossal duct cyst
•Parathyroid cyst/adenoma
((History;Physical Exam ;US&….))
Clinical findings in favor of malignancy
• Historical features:
-Age:<20 or >60
-Male sex
-Neck irradiation(childhood)
-Rapid growth
-Change in speaking;swallowing or breathing
-FH of thyroid malignancy or MEN-2
-The coexistence of any other malignancy, such as HL, non-Hodgkin’s lymphoma or any
other cancer
• Ph.E:
-Firm & irregular consistency
-Fixation
-Vocal cord paralysis
-Regional lymph adenopathy
US findings in favor of malignancy
-Hypoechoic lesion
-Irregular margins
-Calcification
-Absence of halo
-Internal or central blood flow
*Low suspicion
-Echo-Free (cystic) lesion
-Homogeneous hyperechoic lesions
Thyroid nodules in adults
• palpation :3-7% of adults
• More common in women than men(4 times)
• Cysts are the most frequently encountered solitary palpable
nodules.(one-third)
• U/S: 20% of all women
• U/S: 50% of women > 50 y. have nodules
• US:>60% In healthy adults
• In autopsy series:50%
• Increase linearly with:
-Age(0.1% annually)
-Exposure to ionizing radiation(2% annually)
-Iodine deficiency
Thyroid nodules in adults-Cont.
• The most important thing is to distinguish benign from malignant
causes
• the incidence of malignancy is greater in solitary nodules than
multiples.
• Multiple nodules does not imply the nodules are benign.
• Most thyroid nodules are benign(95%)
• Hyper- or hypothyroidism suggests benignity
•
But most patients with thyroid nodules have normal thyroid function tests.
• Possibility of cancer regardless of nodule size is about 5% and its
prevalence is 2-3 times more often in women.
• Nodule size is not predictive of malignancy and cancer is not less
frequent in small size nodules(<10mm)
• Mortality rate is higher in men.
Results of FNA Biopsy
Cytologic Diagnosis
%
Benign
70
Suspicious
10
Malignant
5
Nondiagnostic
15
NONDIAGNOSTIC
*Repeat
Cyst > 4 cm
Diagnostic
Operate
Follow
*%15 of nondiagnostic aspirate may represent malignant nodules.
%50
Benign
LT4
?
Follow
*Suspicious
Malignant
Surgery
*%10 to %20 are malignant at operation.
Cystic nodules
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%15 to %25 of all nodules.
2% to 4% are malignant.
False negative & Nondiagnostic(FNA)
Treat surgically cysts > 4cm.
Half of them disappear after one or more
aspirations.
• Suppressive therapy is ineffective.
Benign thyroid nodule
Observation for 1 year
Thyroid ultrasound
Size decreased
Size unchanged
Size incresed
FNA
Continue observation
Benign nodule
Malignant
or suspicious
LT4 suppression
For 1 year
Ridgway,Ann intern Med 1998
Surgery
Thyroid ultrasound
Size decreased or
unchanged
Continue LT4 therapy
Ridgway,Ann intern Med 1998
Size increased
Surgery
Benign thyroid nodule
Burch,1995
Trial of LT4 therapy
TSH 0.1-0.5 mu/l for 6-12Mo.
Obtain US at baseline and 6-12 Mo.
Larger
Smaller
Unchanged
Surgery
Stop LT4 , observe
Nodule growth
Restart LT4
No change
Follow ,off LT4
Benign thyroid nodule
T4 for 12 Mo. To keep TSH less than 0.1mu/l
Increase in size
D/C T4,Rebiopsy or
surgery
No change in size
D/C T4
Decrease in size
D/C T4 and observe
OR
Decrease T4 to keep TSH
At the low end of NL range
Cooper,1995,JCEM
Thyroid
Cancers
• Incidence :
– (~9/100,000 per year) ;increases with age, plateauing after about
age 50.
– Twice as common in women as men.
– male sex is associated with a worse prognosis.
• Associated with:
– Radiation:
• predisposes to chromosomal breaks, leading to genetic
rearrangements and loss of tumor-suppressor genes.
• It increases the risk of benign and malignant thyroid
nodules,associated with multicentric cancers, and shifts
the incidence of thyroid cancer to an earlier age group
• Children seem more predisposed to the effects of
radiation than adults
• radiation derived from 131I therapy appears to
contribute little, if any, increased risk of thyroid cancer.
Cont.
– TSH and Growth Factors:
• Many differentiated thyroid cancers express TSH
receptors and, therefore, remain responsive to TSH.
– Oncogenes and Tumor-Suppressor Genes:
• cancers are monoclonal in origin(mutations that confer
a growth advantage to a single cell.)
• impaired apoptosis
• Specific mutations for tumor phenotype.
• nonspecific mutations.
Specific cancers
• PTC
• FTC
• MTC
• ATC
• Lymphoma
Papillary Thyroid Cancer
• Most common type (70 to 90% of well-differentiated thyroid malignancies)
- Age: 20-30
• Microscopic PTC :25% of thyroid autopsies.
• Pathogenesis : RET rearrangements
-Activation of receptor tyrosine kinases (RET/PTC, TRK, MET) →Produce
chimeric proteins with tyrosine kinase activity
• BRAF V600E mutation in ~50% of cases(PCR of biopsy - more aggressive
PTC)
• Detection of RET rearrangements by PCR of thyroid biopsies or peripheral
blood in 20 to 40% of PTCs on chromosome 10. (Chernobyl Nuclear
Accident).
• RET translocations cause some papillary cancers.
• Thyroglobulin is an excellent tumor marker.
• TSH dependent?
• APC gene mutation for familial adenomatous polyposis and Gardner’s
syndrome: higher incidence of PTC.
MTC
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~5% of thyroid cancers
malignant tumor of calcitonin-secreting C cells
75% sporadic & 25% hereditary(AD)
Genetical:As a part of either a MEN- 2A or MEN -2B
Familial: MTC without other features of MEN
Variable age (Sporadic/MEN):sixth and seventh decades in sporadic forms.
more aggressive in MEN-2B than in MEN-2A
familial MTC is more aggressive than sporadic MTC
5 to 10% of thyroid cancers
RET mutations in some sporadic cancers.
Calcitonin is an excellent tumor marker
All patients with MTC should be tested for RET mutations. (point
mutations that induce constitutive activity of the tyrosine kinase .)
Follicular Thyroid Cancer
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Less common than papillary
Age 40-50
TSH dependent?
Often caused by a chromosomal translocation fusing the genes
encoding Pax8 (transcription factor) and PPARg (nuclear receptor of
thiazolidinediones)..
Thyroglobulin is an excellent tumor marker
The incidence of FTC varies widely in different parts of the world.
it is more common in iodine-deficient regions.
RAS mutations are found in some FTCs.
Loss of heterozygosity (LOH), consistent with deletions of tumorsuppressor genes, is particularly common in FTC, often involving
chromosomes 3p or 11q.
Anaplastic carcinoma
• Predominantly in persons older than 70 years.
• High mortality:most die < 1 year.
• One third arise in preexisting differentiated
cancers .
• Mutations of the tumor suppressor gene, p53.
Questions?