Pathology of the Thyroid Gland

Question 1

What are the 4 main histological classifications of thyroid cancer?

Answer 1

Papillary - 6%
Follicular - 17%
Medullary - 3%
Anaplastic - 2%

Question 2

What does differentiated thryoid cancer refer to?

Answer 2

Papillary and Follicular thryoid cancer

Question 3

What do most DTCs do?

Answer 3

Take up iodine and secrete thyroglobulin - can act like normal thryoid cells
They are TSH driven

Question 4

Decribe the rates of incidence of DTC in females and males.

Answer 4

Females - Rates increase from 15-40 then plateau

Males - Steady increase with age

Question 5

How do DTC present?

Answer 5

Majority have palpable nodules
small % are chance findings
5% with local or disseminated mets

Question 6

Give 5 points about Papillary thyroid cancer.

Answer 6

Associated with ionising radiation 
Usually solitary nodule 
Activates MAP kinase pathway 
Spreads via lymphatics - lungs, bone, liver and brain
Associated with Hasimoto's thyroiditis

Question 7

Give 4 points about Folicular thyroid cancer.

Answer 7

Associated with iodine deficiency
Usually single slow growing nodule - painless and non-functional
Mutations in PI3K/AKT pathway
Spreads haematogenously

Question 8

What is the prognosis of DTC?

Answer 8

Generally good with 10 year mortality <5%

Question 9

What Ix are used for suspected DTC?

Answer 9

USS guided FNA

Excision biopsy of lumh node

Question 10

What are the clinical predictors of DTC?

Answer 10

New thyroid nodule 50 y.o 
Nodule increased in size 
Male 
Lesion >4cm 
History of head and neck irridation 
Vocal cord palsy - do pre-operative laryngoscopy

Question 11

What exactly is the best management option for DTC?

Answer 11

Sub total thyroidectomy with RAI

Question 12

What risk stratification tool is used post op for patients with DTC and why is this used?

Answer 12

A - age 
M - ets 
E - extent of primary tumour 
S - Size of primary tumour
Used to stratify pts as low or high risk

Question 13

When and why is whole body iodine scanning used?

Answer 13

Pts who have had total or sub-total thyroidectomy
Given low dose iodine capsule which will be taken up by thyroid and any DTC cells in the body to see of tumour all removed or mets

Question 14

If uptake at thyroid bed >0.1% of ingested activity, what does the patient undergo?

Answer 14

Thyroid remnant ablation

then whole body iodine scan repeated to ensure uptake in thyroid bed now <0.1%

Question 15

What can be used as a tumour marker in DTC?

Answer 15

Thyroglobulin - produced by DTC cells and normal thyroid cells but 0 from them as removed

Question 16

What is a follicular adenoma?

Answer 16

Discrete solitary mass derived from thyroid follicular cells encapsulated by a surrounding collagen cuff –> very well circumbscribed

Question 17

Is a follicular adenoma functional or non-functional?

Answer 17

Usually non-functional but can secrete thyroid hormones

Question 18

Can medullary thyroid cancers be familial?

Answer 18

Yes (bilateral/ mulitcentric) or sporadic (solitary nodule)

Question 19

What are medullary thryoid cancers composed of?

Answer 19

Spindle or polygonal cells arranged in nest, trabeculae or follicles

Question 20

What can medullary thyroid cancers cause?

Answer 20

dysphagia
hoarseness
airway compromise

Question 21

Give 4 points about Anaplastic thyroid cancer.

Answer 21

Undifferentiated and aggressive tumours
Usually older patients
May occur in pts with a history of DTC
Rapid growth and involvement of neck structures and death

Question 22

What is the Thy scale and why is it used?

Answer 22

Thy 1 - insufficient sample
Thy 2 - benign
Thy 3 - atypia probably benign/ equivocal
Thy 4 - atypia suspicious of malignancy
Thy 5 - malignant
USS FNA used to provide a minimally invasive assessment of the likelihood of malignancy

Question 23

What can cause primary hyperparathyriodism?

Answer 23

Adenoma involving a single gland or hyperplasia involving all glands

Question 24

What causes secondary hyperparathyroidism?

Answer 24

Chronic hypocalcaemia causes compensatory over activity of parathyroid glands

Question 25

What causes tertiary hyperparathyroidism?

Answer 25

Parathyroid activity becomes autonomous associated with hypercalcaemia

Question 26

What causes hypoparathyroidism?

Answer 26

Usually post-operatively (removal by accident) Rarely congenital absence - DiGeorge syndrome Familial - associated with primary adrenal insufficiency and mucocutaneous candidiasis (AI basis)

Question 27

What is the most common cause of hyper/hpothyroidism?

Answer 27

Autoimmune thyroid disease

Question 28

What blood results would you expect to see from primary hyperthyroidism?

Answer 28

TSH low | T4/T3 high

Question 29

What blood results would you expect to see from primary hypothyroidism?

Answer 29

TSH high | T4/T3 low

Question 30

What blood results would you expect to see from secondary thyroid disease - pituitary gland failure?

Answer 30

TSH low | T4/T3 low

Question 31

What blood results would you expect to see from secondary thyroid disease - TSHoma?

Answer 31

TSH high | T4/T3 high

Question 32

What blood results would you expect to see from primary subclinical hypothyroidism?

Answer 32

TSH high T3/T4 normal Probably end up as overt hypothyroidism

Question 33

Define hypothyroidism.

Answer 33

Results from a variety of abnormalities that cause insufficiet secretion of thryoid hormones

Question 34

What causes primary hypothyroidism?

Answer 34

Iodine deficiency #1 AI - Hashimoto's thyroiditis #1 Hereditary biosynthetic defects Maternally transmitted antithyroid agents, iodides Drug induced - amiodarone, lithium, thalidomide

Question 35

What can cause secondary hypothyroidism?

Answer 35

Hypothalamic - congenital, infiltration, infection, malignancy Pituitary - Panhypopituitarism, isolated TSh deficiency

Question 36

What are the symptoms of hypothyroidism?

Answer 36

``` tiredness/ malaise Weight gain Cold intolerance Goitre Contipation Menorrhagia - later oligo or ammenorrhoea Arthralgia Myalgia Physchosis Poor libido ```

Question 37

What are the signs of hypothyroidism?

Answer 37

``` Dry skin and dry thin hair Periorbital puffiness Pitting oedema Mental slowness Slow relaxing reflexes Carpal tunnel syndrome Hyperprolactinaemia bradycardia worsening of heart failure ```

Question 38

What Ix should be used for hypothyroidism and what would their positive result be?

Answer 38

``` TSH high T4/T3 low Elevated CK Increases LDL cholesterol Hyponatraemia Hyperprolactinaemia Macrocytosis is typical – rule out a concurrent Vit B12 deficiency ```

Question 39

What is Hashimoto's Thyroiditis?

Answer 39

Gradual autoimmune destruction through antibody dependent cell mediated cytotoxicity, of the thyroid gland resulting in decreased thyroid hormone production

Question 40

What autoantibodies are present in Hashimoto's thyroiditis?

Answer 40

Anti-TPO (95%) Anti-thyroglobulin antibody (60%) TSH receptor antibody (10-20% - blocking)

Question 41

How is hypothyrodism managed?

Answer 41

Restore normal metabolic rate gradually younger pts - thyroxine at 50-100mcg daily elderly with history of IHD - thyroxine at 25-50mcg daily - adjusted every 4 weeks according to response

Question 42

In pregnancy the dose requirements of thyroxine increaaase by how much?

Answer 42

25-50% (increased TBG)

Question 43

Who is usually affected by a myxoedema coma?

Answer 43

Elderly women with longstanding but frequently unrecognised/ untreated hypothyrodisim

Question 44

How does a myxoedema coma present?

Answer 44

bradycrdia | type 2 respiratory failure

Question 45

If a patient is on amiodarone, what should they have checked frequently?

Answer 45

TFTs

Question 46

List some causes of Hyperthyroidism

Answer 46

``` Graves disease Multi-nodular goite Toxic nodule (adenoma) Subacute thyroiditis/De Quervains Post-partum thyroiditis Rare - iodine and medications (amiodarone, lithium, kelp) ```

Question 47

List the symptoms of hyperthyroidism.

Answer 47

``` Tremor Palpitations Sweating Irritability Diarrhoea Weight loss Lighter/less frequent periods increased appetite intolerance to heat ```

Question 48

What are the clinical signs of hyperthyriodism?

Answer 48

``` Tachycardia or AF Proximal muscle wasting goitre with bruit warm peripheries lid lag palmar erythema onycholysis ```

Question 49

What are the treatment options for hyperthyriodism?

Answer 49

``` Carbimazole Propylthiouracil Fluid restriction Radioiodine and surgery may also be considered Symptom Tx = beta-blocker (Propanolol) ```

Question 50

What positive investigations indicate Graves disease?

Answer 50

High T3/T4, low TSh Anti-TPO +ve (70-80% Anti-thyroglobulin +ve (30-50%) TSH receptor antibody +ve (70-100% - stimulating)

Question 51

What additional S&S are present in Grave's disease?

Answer 51

``` Exophalmus Chemosis visual loss proptosis diplopia pretibial myxoedema ```

Question 52

What may trigger De Quervains?

Answer 52

Viral infection - other symptoms ay be present - sore throat, fever, etc)

Question 53

What blood results are seen in De Quervains?

Answer 53

T4 - high in early stage, low in late stage then normal | TSH - low in early stage, high in late stage then normal

Question 54

What treatment is required for a thyroid storm?

Answer 54

``` ABCDE May require ventilation Lugol's iodine Glucocorticoids PTU beta-blocker fluids monitoring ```

Question 55

How does a thyroid storm present?

Answer 55

Respiratory and cardiac collapse Hypertermia Exaggerated reflexes

Question 56

What precautions should be followed if you are on radio-active iodine?

Answer 56

avoid close prolonged contact with children and pregnancy women Avoid sharing a bed for x days avoid pregnancy for 6-12 months ensure not pregnant at start high risk of hypothyroidism (esp. in Graves)