AGENDA

• Thyroid
– Anatomy
– Physiology

• EVALUATION
– Morphological
– Functional
– Morphofunctional
– Immunological
– Citological
 Thyroid
• Acinar (ductless alveolar) gland, 10-25 g
• Right + left lobe + isthmus
• Anterior neck, in front of the trachea, below thyroid cartilaje
• Posterior margins abut the oesophagus
• Rich blood supply
– Superior thyroidal arteries (common carotid artery)
– Inferior thyroidal arteries (brachiocephalic artery)
• Innervation: middle/inferior cervical ganglia SNS
• Mesodermal invagination of the pharyngeal floor, Descends
anterior to the trachea (Thyroglossal duct)
• Main hormones: T3, T4 = iodinated Thyrosines (aminic
hormones)
 1 = follicles
2= follicular cells
3 = endothelial cells
 Thyrocytes form hollow spheres (follicles) that surround a central
lumen, containing colloid (iodinated thyroglobulin = hormone store
Follicular cells
•Thyroid hormones

Neuroendocrine cells
•Calcitonin
Thyroid function = dependent of TSH
action
• Iodine

• NIS = transmembranar transporter (TSH mediated)

Iodine: blood NIS intrathyroid (x30-40)

• Thyroglobulin (Tg) = 140 tyrosine residues

Produced by the follicular cell, TSH mediated, at the
Rough endoplasmatic reticulum, glycosylate in the Golgi
apparatus, incorporated in vesicles

• Thyroid peroxidase (TPO) = linkage of Iodine to the

tyrosine residues on Tg, coupling of T1 and T2
 Thyroid hormone synthesis/secretion
1. Active transport of iodine across the basement
membrane
2. Oxidation of the iodine, iodination of tyrosyl
residues (forming iodothyrosine on the Tg surface
= organification = MIT.DIT
3. Linking the pairs of MIT/DIT) to form
iodothyronine (TRIIT /TETRAIT) = coupling
4. Pinocytosis/proteolysis of the thyroglobulin =
release of free MIT/DIT/T3/T4 in the circulation
secretion)
5. Deiodination of the non-used iodothyrosines =
conservation
6. Intrathyroidal deiodination of T4 to T3
Iodination – organification - coupling
 IODINE METABILOSM
• WHO recommendations
Adults 150 mcg iodine intake (Food+ water)
Pregnancy 200 mcg iodine
Lactating 200 mcg iodine
Children 50-250 mcg iodine

Sources: iodized salt, preservatives in baked goods, dairy

products, food containing iodophore antibacterial agents: milk
collection, food coloring, sea food.

Intake < 50 mcg/day = incapacity of sustainable Thyroid Hormones synthesis

 Natural iodine sources I

Soil

• NaIO3 = sodium iodate

• NaIO4 = sodium periodate

Seaweed /plankton

• KI = potassium iodide
• NaI = iodide de sodium
• I2 – iodine
• I = iodide

See water

• I = iodide
Artificial iodine sources I

Salt iodination

Preservatives

Antimicrobial agents
 Iodine food content

Food preparation Iodine content

(mcg/100gr)
Salt (iodinated ) 2000
Seaweed 16-2984
See food 66
Cod 75
Vegetables 32
Meat 26
Eggs 26
Diary products 13
Bread 10
Fruits 4
 almost Exclusively oral intake
ê I
Absorption in small intestine
Skin/lungs
ê
Plasmatic transportation
ê
Preferential thyroidal uptake (NIS)
ê
Urinary excretion (2/3)
 Thyroid hormones transport
• Free 0.03% T4
0.3% T3
• Bound:
– Thyroxin binding globulin TBG 70%
– Transthyretin prealbumin 10-15%
– Albumin 15-20%

1. Pool of hormones
2. Prolongs the half life of the hormone
3. Regulates the free fraction of the hormone
4. Conditionates the metabolic clearance rate
 TBG
é ê
Pregnancy Androgens
Estrogen secreting tumors Glucocorticoids
Estrogens Danazol
5 Fluorouracil L asparaginase
Acute intermittent porphyria Nephrotic sd.
Liver disease Chronic renal failure
Chronic liver disease
Malnutrition
Cushing sd.
Acromegaly
Salicylates, phenytoin, furosemide = displace T3 and T4 from TBG
 Thyroid hormones actions
• T3 = ACTIVE T4 ACTIVATION!!!!!!
• Receptor = genomic/nuclear receptors: T3
• Enzymatic = nongenomic
– Mitochodrial proteins
– Glucose transportes
– Calcium ATPasa
– Adenilat cyclase
• Free fraction = active fraction
• Extrathyroidal T4 è T3 ACTIVATION 1 deiodinase

• CNS T4 è T3 ACTIVATION 2 deiodinase

• Placenta brain T4 è rT3 DEACTIVATION 3 deiodinase

 Thyroid hormones effects I
LEVEL EFFECT
Basal metabolism Stimulates mitochondrial activity
Heat production
Basal metabolism rate
Glycaemic metabolism é Intestinal absorption
é Peripheral consumption
ê hepatic glycogenolysis
ê Insulin sensitivity
Proteic metabolism éProteic synthesis (small doses)
é Protein degradation
Lipid metabolism éLipogenesis
é Triglyceride synthesis – Hypolipemiant éLDL
hepatic clearance
Calcium metabolism Facilitate diuresis
Urinary/fecal Ca loss
Iodine metabolism Almost exclusively controlled by thyroid: NIS
Immunity Favours Ig G synthesis
LEVEL EFFECT
Cardiovascular éInotropism, éCardiac output
éCronotropism
éAdrenergic sensitivity
Pulmonary Maintain ventilatory response to hypoxia/hypercapnia
é Respiratory muscle function
Hematopoetic éErytropoetin /erythropoiesis
Favours 2 dissociation from Hb
Gastrointestinal é Gut motility
Skeletal Bone turnover
Neuromuscular Normal development of CNS
Conditionate the muscle contraction/relaxation
Emotional balance
Skin Trophycity
Fetal development Sustain brain development
Sustain skeletal growth/maturation
Endocrine Normal function of GhRH, GCS metabolism
Thyroid function control
 Main thyroid pathology

Autoimmune diseases = AIT

• Inhibitory AB
• Stimulatory AB

Nodular disease = NG

• Uni/multinodular disease
• Benign/malignant

Iodine deficiency disorders = IDD

• Diffuse goiter
• Nodular transformation
 Evaluation
• Clinical
• Hormonal evaluation: TSH, Ft3, Ft4
• Immunological evaluation: ATPO Ab, ATg Ab, TRAB
• Morphological: Ultrasound evaluation
• Morpho-functional : Scintigraphy
• Dynamic tests: stimulatory = TRH
• Additional test – Calcitonin, Thyroglobulin
• Fine Needle Aspiration Biopsy

• Clinic symptoms scale

• Basal metabolic rate
 CLINICAL = Goiter
• Inspection = patient swallowing
• Palpation
= the thumb anterior along the trachea
= hand on the lobe
= Normal – barely palpable, smooth surface, soft –
rubber consistency diameter 1cm/2cm
Diffuse goiter/nodular goiter
• Auscultation
= increased blood strain
 CLINICAL

1. Compression

2. Hormonal HYPO/HYPER
 HORMONAL - TSH measurement
• assay: periphery venous blood (T1/2 30-50’)
- I-IV generation assays !!! Different sensibility and quality
- Reference range
TSH values
1. Adults: 0.5-4.7 mUI/L
2. children:
1st days of life 70 mUI/L
day 2 to 3 < 10 mUI/L neonatal screening
week 2 to 6 1.7-9.1 mUI/L
2st month < 6 mUI/L
3. Aging 0.5 – 7 mUI/L
 ! Utility of TSH measurement

1. Thyroid dysfunction
2. Neonatal hypothyroidism screening
3. Monitoring of supplemental therapy, in
hypothyroidism cases
4. Evaluation of hyperthyroidism relapse
5. Suppressive therapy in thyroid cancer cases
6. Evaluation of hypophysis tireotrop cells
performance
7. Standard assay in female infertility
8. universal screening> 35 de years, every 5 years
• HORMONAL Always check CENTRAL + PERIPHERY

N TSH N Ft3/fT4 Normal function

ê TSH N Ft3/fT4 SUBCLINICAL HYPER
ê TSH é Ft3/fT4 CLINICAL HYPER
é TSH éFt3/fT4 CENTRAL HYPER
é TSH N Ft3/fT4 SUBCLINICAL HYPO
é TSH êFt3/fT4 CLINICAL HYPO
ê TSH ê Ft3/fT4 CENTRAL HYPO
 IMMUNOLOGICAL - THYROID AB
• Anti TPO Ab = typical for AIT
= should be significantly increased
– Positive diagnostic ONLY

• Anti TIROGLOBULINE Ab = 15% of AT

= 5% of general population

• Anti TSH receptor Ab = typical for Graves disease

– Positive diagnostic
– Disease activity
– Relapse prognostic
– Cure of the disease
 MORPHOLOGICAL = Ultrasound
evaluation
• High resolution US
• LINEAR PROBE 5-15 MHz
• Normal anatomic boundaries
• Used for:
1. search for potential not palpable nodules,
2. to correlate a thyroid disease with clinical symptoms
3. in the presence of anamnestic risk factors for thyroid cancer
4. enlargement of a nodular formation in the cervical region
5. monitor thyroid nodules dynamic/evolution
6. Identify highly suspicious ultrasonographic characteristics
for a thyroid nodule
7. to guide fine needle aspiration
8. postoperative long term follow up
 Ultrasound
• Conventional – grey scale 2 D

• Doppler – color doppler 2D

• Elastography

• Volumetric doppler 3D
 US Application
• Doppler evaluation = degree of thyroid/nodular vascularisation
• Elastography = degree of elasticity in nodules
• 4D = real time tri-dimensional evaluation of nodules
 Golden standard thyroid
evaluation
• Conventional ultrasound
– suspected thyroid nodules
– incidentaloma detected by CT, MRI, FDG-PET
– screening in high risk situations
– suggestive clinical signs
Normal thyroid transversal
Normal thyroid longitudinal
• V = width x length x thickness x / 6 (x 0.5)

W : 10-16 ml
M: 12-20 ml

• + Isthmus if wider than 3 mm

Decreased volume

?
Atrophy
Subtotal lobectomy
postRAIU
postRX therapy
Anatomical variant
Increased volume
?
Autoimmune
Hashimoto
Graves
IDD
Infiltrative disease
Vascularisation

ê
Atrophy
Fibrosis

é
Hyperfuntion – GRAVES
Any situation withé TSH
ê
Atrophy
Fibrosis
POSITION
 Nodular disease
• SHAPE

• MARGINS

• ECOGENEITY

• ±CALCIFICATIONS

• COMPOSITION
TYPICAL BENIGN PATTERN
 SHAPE

Wider than tall Taller than wide

 MARGINS

Well defined Ill defined

 ECOGENICITY

HYPER

IZO
HYPO
 POZITIE
CENTRAL

SUBCAPSULAR
 OMOGENITATE
NEOMOGEN

NEOMOGEN

OMOGEN
CALCIFICARI
 CAPSULE

integral ALTERED
INFLAMATORY lymph nodes

Oval, central simetric hyperecoic hillum

Hipoechoic peripheral rim
REACTIVE lymph nodes

Oval, unclear hillum

Metastatic LYMPH NODES

Round, inomogenous, with microcalcifications

Metastatic LYMH NODES

Round, no central hillum, thyroid like pattern

 VASCULARISATION

decerased

increased
 STIFNESS

Soft lesion

Hard lesion
 Scintigraphy
• Isotopes that are concentrated by thyroid (similar to the natural
Iodine active transport by NIS)
• Measurement f the amount of radiation generated by the exposed
region
• Identifies different behaviour of thyroid territories
• No precise anatomic details/orientative anatomic position:
– 123I orally 8-24 hours
– 99mTc pertechnetat iv 30-60’
– 131I
 INDICATIONS:

1. subclinical or clinic hyperthyroidism, with or

without nodular goiter êTSH

2. suspicion of ectopic goiter

3. suspicion of retro-sternal goiter
4. postoperative assessment in differentiated
thyroid cancers
5. Coexisting of thyroid + parathyroid nodules
 NORMAL ASPECT

„V” shape „U” shape

NORMAL ASPECT
Asimetric irregular
POSITION VARIANTS
ECTOPIC THYROID
ABERANT STRUCTURE
PYRAMIDAL LOBE
ACCESORY LOBE
HYPERFUNTION - UNINODULAR
HYPERFUNTION - MULTIINODULAR
 Other images techniques
• Cervical Rx images - tracheal deviation
• CT and MRI of Neck
– Compressive symptoms
– Tracheal compression
– Esophageal compression
– Not useful for evaluation of intrathyroidal nodules
– Insensitive for intrathyroidal nodules

1. RECOMMENDED for advanced disease

2. RECOMMENDED for invasive primary tumor
3. Regional lymph node estimation ( level VI – I)
• CT of the chest
– Inferior border of the nodule
• FDG-PET is not routinely recommended
– Distant metastases
 CITOLOGY - FNAC

• Clear information
– Benignity reassurance/reconfirmation in low risk
nodules
– Clearance in intermediate risk nodules
– Compulsory in high risk nodules

? Moment of FNAB ç ultrasound nodule selection

RISK SELECTION!!!!!!
 FNA
• US guided
• 23-26 G needle
• Always perpendicular
• RESULTS = BETSEHDA SYSTEM
– I = nondiagnostic
– II = benign
– III = follicular lesion/unclear citology
– IV = follicular neoplasm
– V = suspect malignant
– VI = malignant
Rezultat – BULETIN CITOLOGIC