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THYROID NODULE
THYROID CANCER
Rivka Dresner-Pollak
Endocrinology
Thyroid Nodule
Thyroid Nodule: The new
epidemic
• Prevalence depends on method of detection:
• Palpable nodules
– 1-2% of men and 5-7% of women>age 40
• BY US:
• 7.5 MHz US transducer
– 27% of women; 15% of men
• 10 MHz Us transducer
– 72% of women; 41% of men
THROID NODULE - THE
QUESTIONS:
• Is there cancer? (5-10% of nodules)
• Does it cause hyper-function?
• Is it part of a nodular process in the
thyroid gland ? (Hashimoto’s, Multi
nodular goiter)
Risk Factors for Malignancy
• History:
Recent rapid growth of nodule
Family history of thyroid cancer
Past irradiation to head and neck
• Physical examination:
Vocal cord paralysis
Fixation to adjacent tissue
Cervical lymphadenopathy
Hard, firm nodule
Thyroid nodule investigation- algorithm
Low
TSH
Normal
High
Approach to Thyroid Nodule-1
• 1. First step- measure TSH
• 2. If TSH is suppressed (↓) the thyroid gland is
hyper-functioning
• 3. Look for autonomous nodule by radioactive
scan (iodine 123-I)
• 5% of thyroid nodules are autonomous nodules.
these nodules aren’t cancer!
Normal thyroid scan
HOT HYPERFUNCTIONING
NODULE
• Options for therapy:
– Radioactive iodine OR
– Surgery
Possible complications:
Hypothyroidism (uncommon)
Surgical complications
Thyroid nodule investigation- algorithm
Scan
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
Low
TSH
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
“hot”, “warm” “cold”
Surgery
131I
Rx
Follow-up
Fine needle aspiration biopsy=
FNAB
ATA Clinical Practice Guidelines for
Diagnosis and Management of
Thyroid Nodules
IF TSH is normal fine needle aspiration
(FNA) is indicated for nodules>10 mm. If
<10mm aspirate if clinical risk factors or
suspicious sonographically.
THYROID NODULE
• The size matters!
• US-guided FNA :
detection of additional suspicious nodules
Solid versus cystic areas
Ultrasonographic characteristics:
– Irregular margins
– Intranodular vascular pattern
– Calcification
– Hypoechogenicity
– Halo
Thyroid Ultrasound
• Risk of malignancy of a nodule is increased if:
– Irregular margins
– Intranodular vascular pattern
– Calcification
– Hypoechogenicity
– Halo
Ultrasound
Ultrasound
0.8 cm
solid
1 cm solid
2.5 cm
cystic/solid
What to do with cysts?
•
•
•
•
50-70% do not recur after aspiration
Most cysts are cytologically benign
If no recurrence no need for intervention.
Re-aspirate if they recur (all cystic Papillary
Thyroid Cancers recur)
Thyroid US – FNA FINDINGS
•
•
•
•
60-70% Benign
10 -15% indeterminate or suspicious
Malignant 5-10%
Non-diagnostic 10%
Thyroid histology
Thyroid US – FNA FINDINGS
• 60-70% Benign –repeat US in 6-12
months
• 10 -15% indeterminate or suspicious –
scan; if warm (functioning) may follow
• Malignant 5-10% - surgery total
thyroidectomy
• Non-diagnostic 10% - repeat FNA
Thyroid nodule investigation- algorithm
Scan
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
Low
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
TSH
Normal
High
Treat
hypothyroidism
“hot”, “warm” “cold”
Normal
Surgery
131I
FNAB
“Follicular lesion”
Rx
Scan
Follow-up
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
“warm”
Inadequate Malignant Suspicious
Rebiopsy
Surgery
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
“cold”
What to do with multiple nodules?
• When there are 2 nodules or more aspirate
those with suspicious sonographic
appearance, not necessarily the biggest.
• The risk of malignancy is
the same in a nodule in
MNG as in a
solitary nodule
THYROID CANCER
• Incidence : increasing (over-diagnosis?)
9: 100,000 (females)
• More prevalent in women (2-3:1)
• Very low disease-specific mortality
• Male gender: less favorable prognosis
• Age: >45, less favorable prognosis
Thyroid Cancer
Risk Factors:
• History of external head and neck irradiation
• Radioactive exposure (Chernobil)
Oncogenic syndromes:
Cowden’s syndrome
Familial polyposis
Gardner’s syndrome
Multiple endocrine neoplasia (MEN-2)
• Hashimoto’s disease (papillary, follicular and
lymphoma)
• Areas of Iodine deficiency
THYROID CANCER
• Clinical Presentation-symptomatic or incidental:
• A thyroid nodule–painless, hard, increasing in size
• Found on routine exam. or by the patient
• Cervical lymphadenopathy
• Stridor
• Dysphagia
• Hoarseness
Normal TSH
Lung, bone, liver, brain metastasis (rare)
THYROID CANCER- Classification:
Thyroid epithelial derived cancers:
• 1. Papillary - good prognosis (10 yrs survival
98%)
• 2. Follicular - good prognosis (10 yrs survival
92%)
• 3. Anaplastic - poor prognosis ((10 yrs survival
13%)
1 &2 are differentiated tumors; 3 is undifferentiated
THYROID CANCERS
Other malignant diseases of the thyroid:
1. Medullary thyroid cancer (MTC)
2. Thyroid lymphoma
3. Metastases from breast, colon, renal, melanoma
THYROID CANCER
Diagnosis:
Biopsy from a nodule
(or a lymph node) under US
99% of thyroid cancer patients are euthyroid
(normal TSH, T4 & T3)
A thyroid scan may show a cold nodule
What to do with a Follicular lesion in
Fine Needle Aspiration (FNA)?
• Cytology cannot differentiate between
follicular adenoma and follicular carcinoma.
• If a follicular lesion in cytology and a warm
nodule in a scan, the chance of cancer is
low and follow up is recommended.
• If a follicular lesion in cytology and a cold
nodule in a scan, the chance of cancer is
high and surgery is recommended
ONLY 20% OF COLD NODULES ARE MALIGNANT!
Differentiated Thyroid Cancer
(Papillary and Follicular)
•
•
•
•
•
90% of thyroid carcinomas
Females more than males (2:1)
Median age at diagnosis 30-40 yrs
Frequent metastasis to lymph nodes
Slow growth or no growth over several
months
Staging of papillary and follicular thyroid cancer
Stage
Age <45
Age>45
10-years
mortality
I
Any T, any N, M0
T1, N0, M0
0.5-1.5%
II
Any T, any N, M1
T2,N0, M0
0-9%
T3,N0,M0
T1-3, N1a,M0
T1-3, N1b, M0
T4, any N, any M,
M1, any T, any N
0-9.4%
III
IV
30-90%
T1<2cm,T2:2-4, T3>4 cm, T4 any size, extending beyond thyroid capsule
N0: no nodes; N1: lymph node metastasis, N1b: bilateral, contralateral
M0: no distant metastases M1: distant metastases
THYROID CANCER – Therapy-1
General Principals:
• Surgery
• Radioactive iodine (in some cases)
• Suppression of TSH by thyroxine (T4)
THYROID CANCER – Therapy-2
• 1. Surgery - total thyroidectomy
Complications: recurrent laryngeal
nerve paralysis, hypo-parathyroidism
• 2. Radioactive iodine (I-131) after surgery if:
large tumor >1.5 cm
local invasion to blood vessels/or capsule
local or distant metastasis
Unfavorable histology (follicular)
THYROID CANCER – Therapy-3
•
•
•
•
•
Side effects of radioactive iodine:
Xerostomia
Xerophtalmia
Myelo-suppresion
High cumulative dose (>600 miliCi)
associated with secondary malignancies
THYROID CANCER – Therapy-4
• 3. To prevent re-growth suppress TSH by
L-thyroxine (T4)
target TSH:
TSH 0.05- 0.1 (first yrs and high risk
pts)
0.5-1 long term survivors
THYROID CANCER – Long term
Follow up
Recurrence is most common in the first 5 yrs
- Look for local recurrence -physical exam &
cervical ultrasound
- Serum Tumor Marker:
Thyroglobulin (undetectable if no
recurrence!)
Thyroglobulin (Tg)- a Tumor Marker of
differentiated Thyroid Cancer
• Thyroglobulin (Tg) reflects residual thyroid tissue
• Anti-thyroglobulin antibodies interfere with the
measurement
• Tg is determined on either on thyroxine (Tg-on)
or in response to TSH (Tg-off)
• Elevated TSH is required for Stimulated Tg by:
Stop Thyroxine (TSH>30)
Use recombinant TSH (Tyrogen)
Thyrogen – rhTSH – for diagnosis and
therapy
Options:
• Stop therapy with thyroxine
• pts hypothyroid
• impossible in panhypopituitarism exacerbate
congestive heart failure
• OR
• Thyrogen – rhTSH administered by injection.
• No need to stop thyroxine.
• TSH increases iodine uptake by thyroid tissue.
• For scanning and the delivery of radioactive
iodine for therapy TSH is needed
Anaplastic Thyroid Cancer
• Rapidly growing mass
• Recent hoarseness and stridor
• Pathology – poorly differentiated thyroid
cancer
• No cure. Rapid obstruction of airway and
death
Medullary Thyroid Cancer (MTC)
•
•
•
•
< 10% of thyroid malignancies
Arises from para-follicular cells - C-cells
Secrete Calcitonin- a tumor marker for follow up
Pericapsular and regional lymph node spread is
common
• Spread to lungs, bone, liver via blood stream is
common
• Can produce Carcinoembryonic antigen (CEA)
Medullary Thyroid Carcinoma (MTC)
• Sporadic (80%)
• Hereditary (20%):
– MEN2A (Multiple Endocrine Neoplasia)
– MEN2B
– Famillial MTC
The hereditary form is often bilateral and
preceded by pre- malignant C cell hyperplasia
Total thyroidectomy at the pre-malignant stage
can cure >90% of patients
Medullary Thyroid Cancer (MTC)
•
•
•
•
Mutations in Ret Proto-oncogene – used for
genetic screening and early surgery.
All patients with MTC need RET genetic testing.
A finding of a germ line mutation in RET indicates
a hereditary disease.
Screening of all first degree family members is
indicated.
Gene carriers with the 634 RET mutation (the
most frequent) should undergo prophylactic total
thyroidectomy between 5 and 7 years of age.