Work-up of Solitary Thyroid

Nodule
Dr. Abhishek Vaidya
Embryology
• Begins to form at 17th day
from 1st &2nd pouches
• The glandular primordium
forms a cord which
penetrates floor of oral
cavity, losing connection with
pharynx, reaches anterior
side of trachea
• The tip now bifurcates &
forms 2 lateral lobes
• Duct may persist as
thyroglossal cyst
Surgical Anatomy

• 2 lobes + isthmus
• 20gm
• Conical, 2 x 3 x 5 cm
• Covered by thin capsule
• Overlies 2nd, 3rd, 4th tracheal
rings
• Berry’s ligament attaches
the gland to trachea
• Covered by strap muscles
Blood Supply
Arterial Supply:
• Superior thyroid a.:
Branch of ext. carotid a.
• Inferior thyroid a.: Branch
of thyrocervical trunk
• Thyroidea ima: inconstant
Venous drainage:
• Superior thyroid V.
• Middle thyroid V.
• Inferior thyroid V.
Lymphatic Drainage

1. Central Compartment
2. Lateral Compartment

Central compt. includes

prelaryngeal, pretracheal,
paratracheal LNs
Delimited by innominate
vein inf., trachea
medially, carotid laterally
Nerves in relation to thyroid

• Superior laryngeal n.
• Recurrent laryngeal n.
 INTRODUCTION

 Common clinical problem - prevalence of 4- 7%

 Female : Male = 5 : 1
 2-3% of all cancers in females .
 3 times ↑ risk in females after 35 yrs
 13,000 to 14,000 new cases of ca. thyroid detected every year
 1 in 20 new nodules contain carcinoma
 1 in 200 nodules will be lethal
 Conditions presenting as Solitary Thyroid
Nodule
Common Uncommon
• Colloid Nodule • Thyroid lymphoma
• Thyroid adenoma • Parathy. enlargement
• Thyroid cyst • Abscess/ infection
• Thyroid carcinoma • Agenesis of C/L lobe
• Thyroiditis • Hamartomas
• Asymmetric thyroid • Neurofibroma
enlargement • Amyloid
• Metastatic malignancy
 DILEMMAS OF THE CLINICIAN

 Euthyroid / hyperthyroid / Hypothyroid

 Cold / warm / hot nodule
 Benign / Malignant
 Observation / Medical Rx / Surgical Rx
 Radiation
 DIAGNOSTIC APPROACH
History and Clinical Examination
Thyroid Profile
USG
Fine Needle Aspiration Cytology
Radio Isotope Scan (Thyroid Scan)
- I131 scan, I123 scan & Tc99 scan
Tumour Markers: Tgl, S. Calcitonin, S. Calcium
Radiological Investigations
- X-ray chest / neck –A.P. & Lateral
- High resolution CT Scan
- MRI & PET
All routine investigations for G.A. Fitness
 DIAGNOSTIC APPROACH
HISTORY
- Age / Sex
- Marital status / obstetric history / hormones
- Location-endemic areas / Diet
- H/o radiation in childhood
- History suggestive of hyperthyroidism / hypothyroidism
- Duration of symptoms
- Sudden increase / decrease in size
- Appearance of pain
- Change of voice
- Dysphagia
 DIAGNOSTIC APPROACH
HIGH RISK FACTORS FOR THYROID CANCER

 Nontoxic goitre
 Low / high iodine intake
 Low dose ionising radiation
 Family history of cancer
 History of still birth / miscarriage at pregnancy
 Use of contraception / multiple pregnancy
 DIAGNOSTIC APPROACH
CLINICAL EVALUATION
- Size / rapid increase in size
- Site
- Number –solitary / multi nodular
- Tenderness
- Fixity
- Consistency-solid / cystic / mixed
- Palpable lymph nodes
- For retrosternal ext.: Pemburton’s manoeuvre
- IDL in all patients
 DIAGNOSTIC APPROACH
CLINICAL EVALUATION
High index of suspicion:-
• Size > 4cm
• Higher age: > 45 in female / > 40 in male
• Rapidly growing nodule
• Long standing goitre with sudden increase in size
• Hard in consistency
• Fixed to adjacent structures
• Vocal cord palsy
• Associated lymph nodes
 DIAGNOSTIC APPROACH

Thyroid Function Tests

- Thyroid stimulating hormone (TSH)
- Serum T4 concentration
- Serum T3 concentration
- Free serum T3 / T4
- Antithyroid antibodies tests
 DIAGNOSTIC APPROACH
Thyroid Function Tests

T3,T4 SITE OF EFFECT

TSH

High > 5µg/l Low Primary hypothyroidism thyroid not

produce enough T3,T4
Low < 0.5µg/l Low Hypothyroidism of pituitary origin

Low < 0.1µg/l High Thyrotoxicosis of thyroid origin, Primary

hyperthyroidism
High (rare) High Secondary thyrotoxicosis

Low Normal Subclinical hyperthyroidism

High Normal Subclinical hypothyroidism

Antithyroid antibodies estimation
- Antithyroglobulin antibodies

- Antimicrosomal antibodies

- Antinuclear antibodies
 Antithyroid antibodies estimation

Their levels are used to confirm

- Establishment of disease etiology
- Thyroid disease screening in associated autoimmune
conditions
- Subacute thyroiditis
- Chronic thyroiditis with transient thyrotoxicosis
- Hashimoto’s thyroiditis
- Grave’s disease
 Ultrasonography

• Determine whether - cystic or solid?

- solitary or multinodular?
• Helps to assess difficult to examine neck
• To diagnose hemiagenesis/ contralateral lobe hypertrophy
which can be misdiagnosed
• To assess cervical nodes
• To assess the size after suppression
• It enhances the accuracy of FNAC
 FNAC

• Minimally invasive, quick, highly sensitive and specific

• USG guided FNAC has a higher yield
• Can categorize the nodule as benign/ malignant/ suspicous
• Difficult to opine in cases of follicular neoplasms and Hurthle cell
neoplasms
 FNAC
• False negative: 1 – 6 %
cystic/ hemmorhagic/ hypervascula/ hypocellular – Repeat
FNAC, USG guided if not done earlier

• A series showed cancer in 4% of females and 29% males in false

negative

• False positive: < 5 %

Hashimoto’s/ Grave’s/ toxic goitre
 Thyroid scan
- Site
- Number
- Functional status of the gland

Hot nodule- Hyperfunction- Suspicious autoimmune.

Rarely malignant

Cold nodule- Hypofunction- Suspicion of malignacy

20-30% are malignant.
False positive – found in
degeneration in goitre
99m
Tc:
• Test iodine transport
• Can be done in 1 day
• Less radiation exposure
• Does not penetrate sternum so cant diagnose retrosternal
extension
• Hot nodules on this scan will require I123 scan
I123 scan:
• Tests transport & organification of iodine
• Expensive
• Takes 2 days to complete

I131 scan:
• After total thyroidectomy to assess local regional and
distant metastases
• Patient should be off thyroid supplement
• 2.5 mCi dose is given. After 72 hrs whole body scan is done
Absolute indications for thyroid scan:

• After total thyroidectomy, for diagnosing metastatic

disease

• STN with suppressed TSH: to determine whether nodule is

cold or hot
 TSH Normal TSH Abnormal

Radionuclide Scan

FNAC Not hot Hot

Malignant/Suspicious Benign Treat

as
appropriate
Surgery Follow +/- T4

Growth No growth

Re-evaluate
 Tumour Markers & Genetic Studies
• S. Calcitonin : Done in F/h/o med. ca/ MENII

• S. Calcium: to exclude asso. parathyroid disease

• Ret proto-oncogene mutation: in med. ca/MENII

MENIIa: MTC + Pheo. + hyperparath.
MENIIb: MTC + Pheo. + mucosal neoplasm

• Tgl:
Pre-op: not done
- it cant diff. benign from malignant
- s. antityroglobulin Abs can interfere
Post-op: after total thyroidectomy
- increased TgL suggests mets
- however PET scan is confirmatory
Implications of Tg levels post Total Thyroidectomy

Tg TSH Implication
Undetected High No residual thyroid/
metastasis
Raised Low Residual abnormal thyroid

Low Low Does not exclude metastatic

disease
High High Highly s/o disease

>10 ng/ml or - Investigate for disease

rising Tg
 Serum Tg helps localize site of disease
417 patients: 169 with metastatic disease
pre-TSH post-TSH

10000 2030
687
Serum Tg (ng/mL)

1000
168
100
15 18
8
10 3 2
1
Bones + Lungs + Mediastinum + Cervical LNs
Lowest
Value 8 < 0.6 < 0.6 < 0.6
Robbins, Tuttle et al. JCEM 2004
 CT Scan
To know the relation to adjacent structures like
trachea, larynx, esophagus, CCA, IJV
Retrosternal extension
Assess palpable and impalpable cervical
adenopathy
Tracheal invasion
Local and distant metastatic deposits

Caution: Iodinated contrast to be avoided

 MRI
• Excellent to image lingual thyroid
• Hypervascularity on MRI suggests Grave’s disease and
differentiates from Hashimoto’s disease
• To assess thyroid volume
• Better tumour and muscle interface
• Lymph node assessment
• Since fibrous tissue short T2 weighted relaxation
time/signal density
In absence of PET, MRI is better than CT to differentiate
recurrent or persistant tumour from post-op fibrosis
 Imaging Criteria for Malignancy

• Central hypervascularity
• Hypoechoic nodule
• Irregular borders
• Microcalcifications
• Presence of abnormal nodes
 Tg elevated, -ve I131 scan (TENS)

Lymph node mets Pulmonary/Skeletal mets

USG Neck PET whole body scan

+ ve - ve

FNAC with + ve - ve
Surg. review

Surgery No Sx intervention Single high dose Other conventional

I131 therapy imaging procedures

Positive response No response Other therapy

to treatment to treatment options like
EBRT/ chemo

Follow up on serum Tg
PET Scan:

• Not done as a routine diagnostic work-up

• In a post treatment set-up, it is very useful in detecting a

metastatic lesion / residual lesion

• In an undifferentiated carcinoma, it is more sensitive than

RAI scan

• Expensive, not available universally

 PET as a predictor of outcome
100 RAI Positive FDG PET Positive
Percent Positive Scans

80

60

40

20

0
Well Moderate Poorly Undiff
Degree of Tumor Differentiation
 PROGNOSTIC FACTORS

AGES: Age AMES : Age

Grading Metastasis
Extent Extend
Size Size

MACIS: Metastasis
Age
Completeness of surgery
Invasion of extra-thyroid tissue
Size of primary tumour
 PROGNOSTIC FACTORS

Histological grades
Gx – cannot be assesed
G1 - well differentiated
G2 - mod – well differentiated
G3 - poorly differentiated
G4 - undifferentiated
 PROGNOSTIC FACTORS
AGES Score

AGE 0.05 x age in yrs ( if >/= 40 yrs)

( 1, if < 40 yrs )
GRADE + 1 – if grade II
+ 3 - if grade III or IV
EXTENT + 1 - if extra thyroid
+ 3 - if distant spread
SIZE 0.2 x tumour size ( max diam in cms)
PROGNOSIS BASED ON AGES SCORE
Risk group AGES score Mortality at 25
yrs
Gr I 0 – 3.99 2%
Gr II 4 – 4.99 24%
Gr III 5 – 5.99 49%
Gr IV 6+ 93%
Pathologic types of Thyroid Cancer

Well Differentiated Other Group

Papillary MCT
Follicular Anaplastic
Mixed Lymphoma
Hurthle cell SCC
Sarcoma
Metastatic tumors
Treatment Goals
• Conservation of function
• Surgery has to be tailored according to patient and tumor
factors
• In low grade malignancies conservative surgery, while
aggressive surgery in advanced cancer
 Risk Groups in Thyroid Cancer
Patient Factors Age, Gender
Tumor Factors Grade, Size, ETE, Mets

Low Risk Low risk patient/ low risk tumor

Low risk patient/ high risk tumor
Intermediate Risk
High risk patient/ low risk tumor
High Risk High risk patient/ high risk tumor
Management
• Surgery
• Management of Neck
• Radioactive Iodine (RAI)
• External beam Radiotherapy (EBRT)
 Surgery
• Mainstay of Rx is extirpation of thyroid with minimal
complications
• Controversy is: TOTAL vs HEMI
• Points favouring routine total thyroidectomy:
- Microscopic multicentric disease in opposite lobe in 30-80%
- To allow RAI dosimetry and ablation
- To allow use of Tg as a marker for follow-up
- Theoretical anaplastic transformation of residual thyroid tissue
- ↑ mortality of local recurrence and ↑ complications
of thyroid resurgery
• Points against routine total thyroidectomy:
- Incidence of recurrence in opposite lobe after ipsilateral
lobectomy is only 5 – 7%
- No level I evidence in favour of total thyroidectomy
- ↑ complications and morbidity: RLN & parathyroid injury
- Excellent survival in low and intermediate risk groups
managed by hemithyroidectomy
Locally Advanced Ca.Thyroid
• Well differentiated cancers are rarely invasive
• Structures most commonly required to be removed are Strap ms,
RLN, Larngeal cartilages, Pharyngo-esophageal musculature
• Tracheal involvement:
- Extraluminal: “Shaving” the cartilage
- Endoluminal: sleeve resection and end to end reanastomosis

These paients will require post op EBRT

Management of Neck
• Elective neck dissection is not recommended
• Clinically/radiologically demonstrated nodes must be addressed
• No ‘Berry Picking’
• Suspicious nodes during surgery should be sent for frozen.
• Central compartment dissection with TE groove is preferred for
+ve nodes
• For lateral neck nodal disease, MND type III
• Treated nodal disease in young does not affect prognosis, but in
old there is ↑ risk of neck failure
 Radioactive Iodine
• Ablation of remnant thyroid tissue after total thyroidectomy
• Gross / Microscopic residual disease
• To pick up and treat distant metastases post surgery
• Management of patients presenting with distant metastases
• Adjuvant therapy of bulky nodal disease
 External Beam Radiotherapy
• Anaplastic Ca. thyroid
• MCT with extensive nodal/mediastinal disease
• Residual MCT
• Gross ETE with microscopic residual disease
• Gross residual tumor
• Poorly diff cancer invading central compartment
• High risk DTC patients with high risk tumors
• Selected patients with distant mets
• Certain subtypes (tall cells, scirhous, insular, solid trabecular,
undiiferentiated) which do not concentrate RAI have been
recently treated with EBRT.
 APPROACH TO A THYROID NODULE

CLINICAL EVALUATION
Thyroid Hormone Essay
HYPOTHYROID EUTHYROID HYPERTHYROID
T4 Replacement FNAC ANTITHYROID DRUGS

‘Follicular neoplasm’
DIAGNOSTIC NON - DIAGNOSTIC
FROZEN SECTION
POSITIVE USG GUIDED RE-BIOPSY
SURGERY FOR BAD COSMESIS

BENIGN MALIGNANT SUSPICIOUS

NEGATIVE
T4 SUPPRESSION SCAN

SURGERY WARM COLD >4CM <4CM

FROZEN
SURGERY FOLLOW UP
 Suppressive
Thyroxine in STN

-low risk
-FNAC neg

TFT

T3 / T4 ↓ or TSH ↑

Supression (0.1mg/day)
Level – TSH(0.3-0.5µIU/l
6 mths

If nodule Nodule same or ↑ size

disappears, do TFT

Repeat FNAC
If normal, If TSH high Rx acc to risk criteria
Stop thyroxine Or T3/T4 low
Continue Rx
Parameter Low Intermediate Grade High
Grade Grade
1. Age <45 >45 <45 >45

2. Mets MO MO M+ M+

3.Extrathyroid - - + +
Spread

4. Grade Low grade Low grade High grade/ High

follicular grade/
follicular
5. Size <4 cm <4 cm >4 cm >4 cm

Treatment Hemi- Hemi- Total thyroidectomy +

thyroidectomy thyroidectom removal of extrathyroid
y diseases +I131 therapy.
Surgeons who take
unnecessary risk and
operate by the clock
are exciting from the
on lookers stand point,
but they are not
necessarily those in
whose hands you
would by preference
place yourself .

- Theodor Kocher