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Endocrine > Thyroid Pathology > Flashcards

Thyroid Pathology Flashcards

1
Q

Normal embryological development

A

Develops from evagination of pharyngeal epithelium

Descent from foramen caecum to normal location in anterior neck below larynx along thyroglossal duct

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2
Q

Embryological Abnormalities

A

Failure of descent
–> lingual thyroid

Excessive descent
–> retrosternal location in mediastinum

Thyroglossal duct cyst

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3
Q

Thyroid composition

A

Composed of lobules defined by thin fibrous septa each containing follicles
Each follicle surrounded by flat to cuboidal follicular epithelial cells
Within centre each each follicle is dense amorphous pink material containing thyroglobulin
Occasionally scattered C cells

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4
Q

C cells

A

parafollicular cells
Slightly larger cells with clearer cytoplasm
Secrete calcitonin
Results in lower serum Ca levels (little clinical significance)

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5
Q

Thyroid Function: BMR

A

Increases basal metabolic rate

Hypothalamus produces TRH
TRH stimulates anterior pituitary to release TSH
TSH binds to TSH receptor on surface of thyroid epithelial cells.
G-proteins activated with conversion of GTP to GDP and production of cAMP
cAMP increases production and release of T3 and T4
T3 and T4 circulate in free and bound forms

On release T3 and T4 bind to receptor in target cells

  • complex translocates to nucleus
  • binds to thyroid response elements on target genes
  • stimulates transcription of genes
  • -> increases BMR
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6
Q

Thyroiditis

A

Inflammation of the thyroid gland

Acute: bacterial infection
Subacute (de Quervain’s): Viral infection
Chronic: abnormal immune response

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7
Q

Thyroiditis Autoimmune Disease

A

Hypofunction: Hashimotos Thyroiditis

Hyperfunction: Graves Disease

Susceptibility associated with HLA calotype

Polymorphisms in immune regulation associated genes

  • CTLA-4
  • PTPN-22
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8
Q

Thyrotoxicosis

A

Syndrome occurs as a result of excess T3 and T4

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9
Q

hyperthyroidism aetiology

A 
Graves disease
hyper functioning nodules and tumours 
TSH secreting pituitary adenoma 
Thyroiditis 
Ectopic production
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10
Q

Graves Disease

A

Autoimmune Disorder
- hyperthyroidism

Autoantibodies to TSH receptor, thyroid peroxisomes and thyroglobulin

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11
Q

Anti-TSH receptor autoantibodies (seen in Graves)

A

Thyroid stimulating immunoglobulin
Thyroid growth stimulating Immunoglobulin
TSH binding inhibitor immunoglobulin

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12
Q

Graves Disease features

A

Hyperthyroidism with diffuse enlargement of the thyroid

Eye changes (exophthalmos) 
- results from fibroblasts expressive TSH receptor

Pretibial Myxoedemaa

Follicles contain little or no thyroglobulin

Abundance of lymphoid follicles

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13
Q

Hypothyroidism

A

Symptoms and signs due to low levels of T3 and t4

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14
Q

hypothyroidism aetiology

A 
hashimotos thyroiditis (most common cause) 
iodine deficiency
drugs (lithium)
post therapy
congenital abnormalities

Rare

  • Secondary (pituitary) pathology
  • tertiary (hypothalamic) pathology
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15
Q

Hashimoto Thyroiditis

A

Gradual failure of thyroid function

Autoimmune destruction of thyroid tissue

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16
Q

Hashimotos Thyroiditis Epidemiology

A

Affects middle aged women
Associated with other autoimmune disease
HLA-DR3 and DR5

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17
Q

Anti-thyroid antibodies (hashimotos thyroiditis)

A

Anti-thyroglobulin and anti-peroxidase

When bound cause antibody dependent cell mediated cytotoxicity

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18
Q

Hashimotos Thyroiditis Pathophysiology

A

Antibody dependent cell cytoxicity due to anti-thyroglobulin and anti-peroxidase

CD8+ve cells mediate destruction of thyroid epithelium

Cytokin mediated cell death
- gama interferon from T cell activation recruits macrophages that may damage thyroid follicles

Thyroid may be diffusely enlarged

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19
Q

Hashimotos Thyroiditis: Histology and Follicles

A

Prominent lymphoid infiltrate

  • lymphocytes
  • plasma cells
  • reactive follicles with germinal centres

Thyroid follicles atrophy

  • follicular cells have abundant eosinophilic cytoplasm
  • -> Hurthle cells

may see progressive fibrosis within gland

20
Q

hashitoxicosis

A

Transient hyper function of gland

can precede progressive fibrosis within gland

21
Q

Hashimotos Thyroiditis risks

A

Increased risk of other autoimmune disease

Increased risk of developing B cell NHL in affected glands

22
Q

Goitre

A

Enlargement of thyroid gland

Reduced t3/T4 production causes rise in TSH, stimulating gland enlargement

23
Q

Diffuse goitre

A

T3/T4 normal
TSH elevated

usually euthyroid- present with mass effects

Sporadic

  • F>M
  • Puberty and young adults
24
Q

multi-nodular goitre

A

Evolution from long-standing simple goitre
- recurrent hyperplasia and involution

Variation of response of follicular cells to external stimuli
-mutations of TSH signalling pathway

Ruptures of follicles, haemorrhage, scaring and calcification

Mass Effects: Cosmetics, airway obstruction, dysphagia, compress vessels

May develop autonomous nodule
-hyperthyroid (low risk of malignancy <5%)

25
Q

neoplasms

A

Adenomas
- follicular adenoma

carcinoma

  • papillary
  • follicular
  • medullary
  • anaplastic
26
Q

Adenomas

A

Discrete solitary mass
Encapsulated by a surrounding collagen cuff

Composed of neoplastic thyroid follicles
–> follicular adenoma

Can be difficult to distinguish from

  • dominant nodule in MNG
  • follicular carcinoma
27
Q

Adenomas- function

A

Usually non-functional

Can secreted thyroid hormone

  • thyrotoxicosis
  • -> TSH independent

Functional
-Thyroid adenoma

28
Q

Thyroid Adenomas

A

Mutations of TSHR signalling pathway in functional adenomas

Activating

  • TSHR
  • G-proteins

Increase cAMP levels

29
Q

Carcinomas epidemiology

A

Can affect any age group

- female predominance

30
Q

Thyroid malignancy

A

Most are well differentiated and derived from follicular epithelium
(Medullary from C cells)

Carcinomas

  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
31
Q

Carcinoma Aetiology (Environment Associations)

A

Ionising Radiation
- Papillary carcinoma

Iodine Deficiency
- follicular carcinoma

32
Q

Carcinoma Aetiology (genetic Features)

A

Papillary: Activate MAP kinase pathway

  • Rearrangements of RET or NTKR1
  • Activating point mutation in BRAF
  • Mutation of RAS

Follicular

  • Mutations in P13k/ AKT pathway
  • Mutation in ras family
  • translocation involving Pax8 and PPAR-gamma-1

Anaplastic

  • features of. above types
  • p53 and B-catenin

medullary
-MEN2

33
Q

Papillary carcinomas

A

Most common type of thyroid cancer

Usually solitary nodule

  • can be multifocal
  • often cystic
  • may be calcified: psammoma bodies

Sometimes present with lymph node metastasis

34
Q

Papillary carcinoma presentation

A

Lesion in thyroid gland or cervical lymph node mass

Local effects

  • hoarseness
  • dysphagia
  • cough
  • dysponoea

haematogenous spread is uncommon
- usually to lungs

Overall good survival rates

35
Q

Follicular carcinoma epidemiology

A

Females> Males

Older than with papillary (40s and 50s0)

36
Q

Follicular Carcinoma Presentation

A

Usually single nodule
- slowly enlarging, painless and non-functional

Rare lymphatic spread

Propensity from haematogenous spread
-bones, lungs, liver

invasive growth pattern

37
Q

Follicular Carcinoma Prognosis

A

Depends on extent of invasion and stage of presentation

High stage at presentation
-50% mortality art 10 years

Minimally invasive lesions
- >90% survival at 10 years

38
Q

Medullary Thyroid Carcinoma

A

Relatively rare

Derived from C-cells (neuroendocrine)
- secrete calcitonin

39
Q

Medullary thyroid carcinoma aetiology

A

Sporadic: solitary nodule

Associated with Men IIA or IIB

Familial medullary carcinoma

Familial cases: bilateral or multi centric
- C-cell hyperplasia

40
Q

Medullary thyroid carcinoma composition

A

Composed of spindle or polygonal cells arranged in nests, trabecular or follicles

41
Q

Medullary Thyroid Carcinoma Associations

A

Associated amyloid deposition

Amyloid represents deposition of abnormally folded protein: calcitonin

42
Q

Medullary Thyroid Carcinoma presentation

A

neck mass with local effects

  • dysphagia
  • hoarseness
  • airway compromise

paraneoplastic Syndrome

  • diarrhoea (VIP production)
  • Cushings (ACTH production0
43
Q

medullary thyroid carcinoma mangement

A

Total thyroidectomy
Local recurrence in 35%

Good prognostic factors

  • young age, female
  • tumour size, confined to thyroid, no. mets

MENIIB has more aggressive potential

44
Q

Anaplastic Carcinoma

A

Undifferentiated and aggressive tumours

45
Q

Anaplastic Carcinoma Presentation

A

Usually older patients
may occur in people with a history of differentiated thyroid cancer

Rapid growth and involvement of neck structures and death

Endocrine (25 decks)

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