The ThyroidThe Thyroid

Goals and ObjectivesGoals and Objectives

• Review thyroid anatomy and function• Present sweet case• Discuss pathology related to sweet case

• Review thyroid anatomy and function• Present sweet case• Discuss pathology related to sweet case

Anatomy 101Anatomy 101

Closer…Closer…

Closer still…Closer still…

• Too close• Too close

Not quite as close…Not quite as close…

Thyroid Function in ReviewThyroid Function in Review

Key PlayersKey Players

• TRH– From parvocellular neurons of hypothalamus

• TSH– From basophilic cells of anterior pituitary

• Thyroglobulin– Stores T1-T4 in colloid

• T4– More common– More potent

• T3– More common– More potent

• Calcitonin

• TRH– From parvocellular neurons of hypothalamus

• TSH– From basophilic cells of anterior pituitary

• Thyroglobulin– Stores T1-T4 in colloid

• T4– More common– More potent

• T3– More common– More potent

• Calcitonin

Normal ThyroidNormal Thyroid

When good thyroids go badWhen good thyroids go bad

• Hypofunctioning• Hyperfunctioning• Neoplasia

• Hypofunctioning• Hyperfunctioning• Neoplasia

The CaseThe Case

1950s1950s

What can’t be radiated?What can’t be radiated?

• Therapeutic irradiation– Acne– Excessive facial hair– Tuberculosis of the neck– Fungal diseases of the scalp– Sore throat– Chronic cough– Enlargement of thymus, tonsils, adenoids

• Therapeutic irradiation– Acne– Excessive facial hair– Tuberculosis of the neck– Fungal diseases of the scalp– Sore throat– Chronic cough– Enlargement of thymus, tonsils, adenoids

20022002

• CC: neck mass, fatigue• TSH 0.42, free T4 1.1 138 102 15 8.5

94 3.7 28 1.0

• FNA– benign colloid goiter

• CC: neck mass, fatigue• TSH 0.42, free T4 1.1 138 102 15 8.5

94 3.7 28 1.0

• FNA– benign colloid goiter

20032003

• Breast cancer (left)– Surgical resection

• Adenocarcinoma• ER/PR positive

– Chemotherapy• Faslodex• Zometa

• CT-chest…

• Breast cancer (left)– Surgical resection

• Adenocarcinoma• ER/PR positive

– Chemotherapy• Faslodex• Zometa

• CT-chest…

20052005

• CT-chest– Large heterogeneous mass at

thoracic inlet with tracheal deviation to the left

– Innumerable lung nodules (2mm-1.5cm)

– Rib lesion…• Metastatic adenocarcinoma (ER/PR+)

• CT-chest– Large heterogeneous mass at

thoracic inlet with tracheal deviation to the left

– Innumerable lung nodules (2mm-1.5cm)

– Rib lesion…• Metastatic adenocarcinoma (ER/PR+)

20052005

• Thyroid U/S– Right lobe, 5.8x3.6x8.6cm

• Superior nodule, 5.2x2.9x3.8cm• Inferior nodule, 4.9x3.8x5.3cm

– Isthmus• Nodule, 4.6x2.2x6.9cm

– Left lobe, 2.2x1.9x5.3cm• Lower, 1.6x1.6x1.6cm• Mid, 0.9x1.0x0.9cm

• Thyroid U/S– Right lobe, 5.8x3.6x8.6cm

• Superior nodule, 5.2x2.9x3.8cm• Inferior nodule, 4.9x3.8x5.3cm

– Isthmus• Nodule, 4.6x2.2x6.9cm

– Left lobe, 2.2x1.9x5.3cm• Lower, 1.6x1.6x1.6cm• Mid, 0.9x1.0x0.9cm

20052005

• FNA– Right lobe

• Upper: benign colloid goiter• Lower: benign colloid goiter

– Isthmus• Benign colloid goiter

– Left lobe• Lower: benign colloid goiter• Mid: papillary carcinoma

• FNA– Right lobe

• Upper: benign colloid goiter• Lower: benign colloid goiter

– Isthmus• Benign colloid goiter

– Left lobe• Lower: benign colloid goiter• Mid: papillary carcinoma

20062006

• CC: fatigue, dry skin• Neck mass enlarging• TSH 0.11, free T4 4.4, free T3 5.9• Thyroglobulin 292.8 [3-40]• CT-chest/abd/pelvis

– Thoracic inlet mass has neck extension

• CT-neck…

• CC: fatigue, dry skin• Neck mass enlarging• TSH 0.11, free T4 4.4, free T3 5.9• Thyroglobulin 292.8 [3-40]• CT-chest/abd/pelvis

– Thoracic inlet mass has neck extension

• CT-neck…

20062006

• CT-neck– 9.0x6.4x7.9cm, poorly defined mass– Tracheal compression and invasion

• Subtotal thyroidectomy…

• CT-neck– 9.0x6.4x7.9cm, poorly defined mass– Tracheal compression and invasion

• Subtotal thyroidectomy…

20062006

• Subtotal thyroidectomy– Papillary carcinoma, T4aNxMx

• Thyroid body scan– Thyroid uptake 14%– No visible mets, but sensitivity decreased

• Remaining thyroid tissue• Normal TSH

• 29 mCi I131 delivered

• Levothyroxine started

• Subtotal thyroidectomy– Papillary carcinoma, T4aNxMx

• Thyroid body scan– Thyroid uptake 14%– No visible mets, but sensitivity decreased

• Remaining thyroid tissue• Normal TSH

• 29 mCi I131 delivered

• Levothyroxine started

20072007

• Thyroid body scan– Thyroid uptake 4%– Diffuse lung mets

• 143 mCi I131 delivered• Thyroid body scan

– Thyroid uptake 1.6%– Lung uptake 15%– Left femur/hip lesion?

• 75 mCi I131 delivered• TSH 4.92 (0.69), Thyroglobulin 175.0

(108.4)

• Thyroid body scan– Thyroid uptake 4%– Diffuse lung mets

• 143 mCi I131 delivered• Thyroid body scan

– Thyroid uptake 1.6%– Lung uptake 15%– Left femur/hip lesion?

• 75 mCi I131 delivered• TSH 4.92 (0.69), Thyroglobulin 175.0

(108.4)

2008 and Beyond2008 and Beyond

• ???• ???

Thyroid CancerThyroid Cancer

The TypesThe Types

Thyroglobulin Calcitonin

Papillary Positive Negative

Follicular Positive Negative

Medullary Negative Positive

Anaplastic Negative Negative

PapillaryPapillary

FollicularFollicular

MedullaryMedullary

AnaplasticAnaplastic

Risk FactorsRisk Factors

• Radiation– Low- or high-dose– 40-50 Gy– Ionizing radiation– X-ray– Radiotherapy

• Iodine deficiency• Family history?

• Radiation– Low- or high-dose– 40-50 Gy– Ionizing radiation– X-ray– Radiotherapy

• Iodine deficiency• Family history?

What’s a Gy?What’s a Gy?

• Gray• 1975: Louis Harold Gray

(1905-1965)• Absorption of one joule

of radiation energy by one kilogram of matter

• 100 rad

• Gray• 1975: Louis Harold Gray

(1905-1965)• Absorption of one joule

of radiation energy by one kilogram of matter

• 100 rad

How much is 40-50 Gy?How much is 40-50 Gy?

• 10-20 Gy at once = fatal• Abdominal x-ray = 1.4 mGy• CT-abd/pelvis = 30 mGy• 1000m from Nagasaki = 9-10 Gy

• 10-20 Gy at once = fatal• Abdominal x-ray = 1.4 mGy• CT-abd/pelvis = 30 mGy• 1000m from Nagasaki = 9-10 Gy

EpidemiologyEpidemiology

• 1.5% of all cancers worldwide• Mean survival 90% at 10 years• 70% papillary• 10-15% present with lymph node or lung mets• Female predominance

– Age > 45 = 2.8:1

• 1.5% of all cancers worldwide• Mean survival 90% at 10 years• 70% papillary• 10-15% present with lymph node or lung mets• Female predominance

– Age > 45 = 2.8:1

PresentationPresentation

• Common– Asymptomatic

mass– Cough– Dypsnea– Dysphagia

• Common– Asymptomatic

mass– Cough– Dypsnea– Dysphagia

• Rare– Pain– Stridor– Vocal cord

paralysis– Rapid

enlargement

• Rare– Pain– Stridor– Vocal cord

paralysis– Rapid

enlargement

PathophysiologyPathophysiology

• trk proto-oncogene– Tyrosine kinase

• ret proto-oncogene– “Rearranged during transfection”

• trk proto-oncogene– Tyrosine kinase

• ret proto-oncogene– “Rearranged during transfection”

Lab workLab work

• T4• T3• TSH• Thyroglobulin• Calcium• Calcitonin• CEA• TSH suppression test

• T4• T3• TSH• Thyroglobulin• Calcium• Calcitonin• CEA• TSH suppression test

Other InvestigationsOther Investigations

• Plain films, CT, MRI• Echography• Scintography• FNAB

• Plain films, CT, MRI• Echography• Scintography• FNAB

HistologyHistology

• Orphan Annie eyes• Psammoma bodies

• Orphan Annie eyes• Psammoma bodies

StagingStaging

• Less than 45– Stage I

• Any T, any N, M0

– Stage II• Any T, any N, M1

• Less than 45– Stage I

• Any T, any N, M0

– Stage II• Any T, any N, M1

• Over 45– Stage I

• T1, N0, M0– Stage II

• T2, N0, M0• T3, N0, M0

– Stage III• T4, N0, M0• Any T, N1, M0

– Stage IV• Any T, any N, M1

• Over 45– Stage I

• T1, N0, M0– Stage II

• T2, N0, M0• T3, N0, M0

– Stage III• T4, N0, M0• Any T, N1, M0

– Stage IV• Any T, any N, M1

TreatmentTreatment

• Surgical resection– Lobectomy– Subtotal thyroidectomy– Total thyroidectomy

• Radioablation– Non-metastatic: 30-100 mCi q3wk– Metastatic: 150-200 mCi q3wk

• External beam radiation• Thyroid replacement• Chemotherapy

– Cisplatin– Doxorubicin

• Surgical resection– Lobectomy– Subtotal thyroidectomy– Total thyroidectomy

• Radioablation– Non-metastatic: 30-100 mCi q3wk– Metastatic: 150-200 mCi q3wk

• External beam radiation• Thyroid replacement• Chemotherapy

– Cisplatin– Doxorubicin

SummarySummary

• Number of iodine molecules in the most metabolically active thyroid hormone?– Three

• Most common thyroid cancer?– Papillary

• Greatest risk for thyroid cancer?– Radiation exposure

• Treatment for thyroid cancer?– Resection and radioablation

• Number of iodine molecules in the most metabolically active thyroid hormone?– Three

• Most common thyroid cancer?– Papillary

• Greatest risk for thyroid cancer?– Radiation exposure

• Treatment for thyroid cancer?– Resection and radioablation

The EndThe End