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Pathology of the thyroid Flashcards

1
Q

What level does the thyroid sit at?

A

C5/6 - T1

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2
Q

How heavy is the thyroid gland?

A

15-25g

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3
Q

How does the thyroid develop embryologically?

A

Evagination of pharyngeal epithelium

Descent from foramen caecum to normal location along thyroglossal duct

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4
Q

What can cause a lingual thyroid?

A

Failure of descent

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5
Q

What can cause a retrosternal location thyroid in the mediastinum?

A

Excessive descent

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6
Q

What composes the thyroid histologically?

A

Follicles that are surrounded by flat to cuboidal epithelial cells. Within the centre of each follicle is a dense amorphic pink material (colloid) containing thyroglobulin
Scattered C cells (parafollicular cells)

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7
Q

What do C cells secrete?

A

Calcitonin

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8
Q

What is the hormone release axis of the thyroid?

A

Hypothalamus singals to anterior pituitary via TRH to release TSH
TSH acts on the thyroid gland to release T3 and T4

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9
Q

What is the negative feedback loop for the thyroid gland?

A

T3/4 act on the anterior pituitary and hypothalamus to prevent the release of TSH and TRH

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10
Q

How does TSH stimulate thyroid hormon release?

A

Binds to TSH receptors on the surface of thyroid epithelial cells
This activates G proteins with the conversion of GTP to GDP and the production of cAMP

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11
Q

What does cAMP do in the follicular cells?

A

It increases the production and release of T3 and T4

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12
Q

What will T3 and T4 do?

A

Bind to nucleus in target cells via hybrid nuclear receptors
Binds to thyroid response elements on these enes
Stimulate transcription of these genes that regulate the BMR

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13
Q

What can an enlargement of the thyroid gland present as?

A

Mass effect - stridor, dysphagia

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14
Q

What autoimmune disease causes hypothyrodism?

A

Hashimoto’s thyroditis

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15
Q

What autoimmune disease causes hyperthyrodism?

A

Grave’s disease

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16
Q

What polymorphisms are present in hashimoto’s thyroditis?

A

CTLA-4 - negative regulator of T cell responses,

PTPN-22 - inhibitis T cell response

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17
Q

What are the other causes outwith autoimmune diseases that cause thyroid problems?

A 
Infection
Palpation
Subactue lymphocytic 
de Quervian's 
Ridel's
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18
Q

What will the thyroid gland be like in Ridel’s?

A

Associated with fibrosis with a hrad/craggy gland that mimics a malignancy

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19
Q

What can cause hyperthyrodism?

A 
85% grave's 
Hyperfunctioning nodules and tumours
TSH secreting pituitary adenoma 
Thyroditis
Ectopic production (stuma ovarii) 
Factitious (exogenous intake)
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20
Q

Who is grave’s disease likely to affect?

A

10F:1M

20-40 years oldd

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21
Q

What antibodies will be present in grave’s disease?

A

Anti-TSH - thyroid stimulating immunoglobulin

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22
Q

What is the triad of features associated with grave’s disease?

A

Hyperthyrodism with diffuse enlargement of the thyroid
Eye changes
Pretibial myoxdema

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23
Q

What does grave’s disease look like histologically?

A

Many lymphoid cells
Thyroid follicles that lack colloid
Colloid scalloping

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24
Q

What is hypothyrodism?

A

Symptoms and signs due to low levels of T3 and T4

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25
Q

What is the main pathology causing hypothyrodism?

A

Hashimoto’s thyroditis

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26
Q

Who is likely to get hashimoto’s thyroditis?

A

Middle aged women

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27
Q

What genetic associations are there with hashimoto’s thyroditis?

A

HLA-DR3

DR5

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28
Q

What else apart from hashimotos can cause hypothyrodidism?

A 
Iodine deficiency
Drugs (lithium) 
Post therapy (surgery, irradiation)
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29
Q

What thyroid antibodies are associated with hashimoto’s?

A

Anti-thyroglobulin

Anti-peroxidase

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30
Q

What happens immunologically in hashimoto’s?

A

CD8+ T cells mediate destruction dependent cell mediated toxicity
Gamma interferon from T cell activation recruits macrophages that may damage thyroid follicles

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31
Q

What is hashitoxicosis?

A

Transient hyperthyrodidsm before hypothyrodism

32
Q

What is a goitre?

A

Any enlargement of the thyroid gland

33
Q

What increased risk is there in the gland in hasimotos?

A

B cell NHL

34
Q

What is the commenest cause of a goitre?

A

Lack of dietary iodine

Reduced T3/4 production causing a rise in TSH, stimulatin gland enlargement

35
Q

What will the thyroid function tests look like in a diffuse goitre?

A

T3/4 normal but TSH high or upper limit of normal

36
Q

What can cause a diffuse goitre?

A

Sporadic - females and young adults
Ingestion of substances limiting T3/4 production
Inborn errors (dyshormonogenesis)

37
Q

What will a multi-nodular goitre look like?

A

Rupture of follicles, haemorrhage, scarring and calfication

38
Q

What is the benign tumour of the thyroid?

A

Follicular adenoma

39
Q

What carcinomas can occur in the thyroid?

A

Papillary
Follicualr
Meduallary
Anaplastic

40
Q

What will a follicular adenoma look like?

A

Incidentla finding
Encapsulated by a surrounding collagen cuff
Composed of neoplastic thyroid follicles

41
Q

What can a follicualr adenoma resemble?

A

Dominant nodule in multinodualr goitre

Follicular carcinoma

42
Q

What can a follicualr adenoma secrete?

A

Thyroid hormones

TSH independent

43
Q

What mutation is associated with thyroid adenomas?

A

RAS or PIk3CA

Mutations in TSHR signalling pathway in functional adenomas

44
Q

What iwll functional adenomas do to the signalling pathway?

A

Activate TSHR
G proteins
Increase cAMP levels

45
Q

What cells do medullary carcinomas develop from?

A

C cells - calcitonin

46
Q

What are the environmental associations of papillary carcinomas?

A 
Ionising radiation (papillary carcinoma) 
Iodine deficiency (follicular carcinoma)
47
Q

What are the genetic features of a papillay carcinoma?

A

Activate MAP kinase pathway with an activaing point mutation in BRAF and ras

48
Q

What are the genetic features of a follicular carcinoma?

A

Mutations in P13K/ AKT pathway

Mutations in ras family (usually N-ras)

49
Q

What are the genetic features of an anaplastic carcinoma?

A

p53 and beta catenin mutations

50
Q

What are the genetic features of a medullary carcinoma?

A

MEN2 - germline RET mutations

51
Q

What is the commonest form of thyroid cancer?

A

Papillary carcinoma

52
Q

How will a papillary carcinoma present?

A

Solitary nodule in thyroid
Can be mutifocal
Often cystic
May be calcified: psammoma bodies

53
Q

Where can papillary carcinomas metastasize to?

A

Lymph node mets

Thyroid tissue or psammoma body in lymph nodes

54
Q

How will a papillary carcinoma present?

A

Lesion in thyroid gland or cervical lymph node mass

Local effects: hoarseness, dysphagia, cought, dyspnoea

55
Q

Where will papillary carcionmas spread haematogenously?

A

Lung but uncommon

56
Q

What is the second most common thyroid cancer?

A

Follicular carcinoma

57
Q

How will a follicular carcinoma grow?

A

Slowly enlarging, painless non functional single nodule

Rarely lymoh spread but will spread to bone, lungs and liver

58
Q

What is the histological features of a widely invasive follicular carcinoma?

A

More solid architecture
Less follicular architecture
More mitotic activity

59
Q

What is the histological features of a minimally invasive follicular carcinoma?

A

Follicular architecture (well differentiated)
May have part surrounding capsule
Difficult to distinguish from adenoma

60
Q

What will a medullary carcinoma look like histologically?

A

Spindle or polygonal cells arranged in nests, trabeculae or follicles
Associated with amyloid deposition - represents deposition of an abnormally folded protein

61
Q

How will a medullary carcinoma present?

A

Neck mass with local effects - dysphagia, hoarseness, aiway compromise

62
Q

What paraneoplastic syndromes are associated with medullary carcinomas?

A

Diarrhoea (VIP production)

Cushings (ACTH production)

63
Q

How is a medullary carcinoma treated?

A

Total thyriodectomy

64
Q

What are good prognostic factors in medullary carcinoma?

A

Young age
Familial setting
Tumour size and is confined to the gland

65
Q

What suggests an aggressive tumour in a medullary carcinoma?

A

Necrosis
Many mitoses
Small cell morphology

66
Q

What is an anaplastic carcinoma?

A

Undifferentiated and aggressive tumour

67
Q

Who is an anaplastic carcinoma likely to affect?

A

Usually older patients

In people with a history of differentiated thyroid cancer

68
Q

What are the different scales for thyroid cytology?

A 
Thy 1- insufficient 
Thy 2 - benign 
Thy 3 - atypia probably benign / equivocal 
Thy 4 - atypia suspicous of malignancy 
Thy 5 - malignant
69
Q

What cells compose parathyroid cells?

A

Chief cells

Oxyphil cells - slightly larger cells with acidophilic cytoplasm

70
Q

What does the parathyroid group do?

A

Secretes PTH
Act on Ca homeostasis
Round cells with moderate cytoplasma and bland round central nuclei

71
Q

What is the commonest pathology of hyperparathyrodism?

A

Small adenomas

72
Q

What can hyperplasia of the parathyroid gland be associated with?

A

MEN 1

MEN 2a

73
Q

What causes secondary hyperparathyroidism?

A

Chronic hypocalcaemia causes compensatory over activity of the parathyroid glands - renal failure, low calcium intake, vitamin D deficiency, parathyroid tissue hyperplastic

74
Q

What causes tertiary hyperparathyroidism?

A

Parathyroid activity becomes autonomous

Associated with hypercalcamia

75
Q

What can hyperparathyroidism cause?

A

Bone disease (pain, fracture, osteoporosis)
Nephrolithiasis (renal stones, complications)
Gi complications (constipation, nausea, peptic ulcer, pancreatitis, gall stones)
CNS (depression, lethargy, seizures)
Neuro-muscluar (weakness and fatigue)
CVS (calcification of aortic and mitral valves)

76
Q

When can you get hypoparathyroid?

A

Post-op

Di George 22q11.2

77
Q

What are the sympoms of hypoparathyroidism?

A

Tetany
Altered mental state
Basal ganglia calcification, parkinsonian, raised ICP, papillodedma
Calcification of lens and cataract formation
Prolong QT interval in ECG
Dental abnormalities

Endocrine (35 decks)

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