Pathology of the thyroid Flashcards by Joanna Mitchell

What level does the thyroid sit at?

C5/6 - T1

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How heavy is the thyroid gland?

15-25g

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How does the thyroid develop embryologically?

Evagination of pharyngeal epithelium

Descent from foramen caecum to normal location along thyroglossal duct

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What can cause a lingual thyroid?

Failure of descent

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What can cause a retrosternal location thyroid in the mediastinum?

Excessive descent

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What composes the thyroid histologically?

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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What do C cells secrete?

Calcitonin

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What is the hormone release axis of the thyroid?

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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What is the negative feedback loop for the thyroid gland?

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

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How does TSH stimulate thyroid hormon release?

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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What does cAMP do in the follicular cells?

It increases the production and release of T3 and T4

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What will T3 and T4 do?

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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What can an enlargement of the thyroid gland present as?

Mass effect - stridor, dysphagia

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What autoimmune disease causes hypothyrodism?

Hashimoto’s thyroditis

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What autoimmune disease causes hyperthyrodism?

Grave’s disease

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What polymorphisms are present in hashimoto’s thyroditis?

CTLA-4 - negative regulator of T cell responses,

PTPN-22 - inhibitis T cell response

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

Infection
Palpation
Subactue lymphocytic 
de Quervian's 
Ridel's

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

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

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What can cause hyperthyrodism?

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

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Who is grave’s disease likely to affect?

10F:1M

20-40 years oldd

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What antibodies will be present in grave’s disease?

Anti-TSH - thyroid stimulating immunoglobulin

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

Hyperthyrodism with diffuse enlargement of the thyroid
Eye changes
Pretibial myoxdema

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What does grave’s disease look like histologically?

Many lymphoid cells
Thyroid follicles that lack colloid
Colloid scalloping

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What is hypothyrodism?

Symptoms and signs due to low levels of T3 and T4

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What is the main pathology causing hypothyrodism?

Hashimoto's thyroditis

Who is likely to get hashimoto's thyroditis?

Middle aged women

What genetic associations are there with hashimoto's thyroditis?

HLA-DR3 | DR5

What else apart from hashimotos can cause hypothyrodidism?

``` Iodine deficiency Drugs (lithium) Post therapy (surgery, irradiation) ```

What thyroid antibodies are associated with hashimoto's?

Anti-thyroglobulin | Anti-peroxidase

What happens immunologically in hashimoto's?

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

What is hashitoxicosis?

Transient hyperthyrodidsm before hypothyrodism

What is a goitre?

Any enlargement of the thyroid gland

What increased risk is there in the gland in hasimotos?

B cell NHL

What is the commenest cause of a goitre?

Lack of dietary iodine | Reduced T3/4 production causing a rise in TSH, stimulatin gland enlargement

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

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

What can cause a diffuse goitre?

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

What will a multi-nodular goitre look like?

Rupture of follicles, haemorrhage, scarring and calfication

What is the benign tumour of the thyroid?

Follicular adenoma

What carcinomas can occur in the thyroid?

Papillary Follicualr Meduallary Anaplastic

What will a follicular adenoma look like?

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

What can a follicualr adenoma resemble?

Dominant nodule in multinodualr goitre | Follicular carcinoma

What can a follicualr adenoma secrete?

Thyroid hormones | TSH independent

What mutation is associated with thyroid adenomas?

RAS or PIk3CA | Mutations in TSHR signalling pathway in functional adenomas

What iwll functional adenomas do to the signalling pathway?

Activate TSHR G proteins Increase cAMP levels

What cells do medullary carcinomas develop from?

C cells - calcitonin

What are the environmental associations of papillary carcinomas?

``` Ionising radiation (papillary carcinoma) Iodine deficiency (follicular carcinoma) ```

What are the genetic features of a papillay carcinoma?

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

What are the genetic features of a follicular carcinoma?

Mutations in P13K/ AKT pathway | Mutations in ras family (usually N-ras)

What are the genetic features of an anaplastic carcinoma?

p53 and beta catenin mutations

What are the genetic features of a medullary carcinoma?

MEN2 - germline RET mutations

What is the commonest form of thyroid cancer?

Papillary carcinoma

How will a papillary carcinoma present?

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

Where can papillary carcinomas metastasize to?

Lymph node mets | Thyroid tissue or psammoma body in lymph nodes

How will a papillary carcinoma present?

Lesion in thyroid gland or cervical lymph node mass | Local effects: hoarseness, dysphagia, cought, dyspnoea

Where will papillary carcionmas spread haematogenously?

Lung but uncommon

What is the second most common thyroid cancer?

Follicular carcinoma

How will a follicular carcinoma grow?

Slowly enlarging, painless non functional single nodule | Rarely lymoh spread but will spread to bone, lungs and liver

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

More solid architecture Less follicular architecture More mitotic activity

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

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

What will a medullary carcinoma look like histologically?

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

How will a medullary carcinoma present?

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

What paraneoplastic syndromes are associated with medullary carcinomas?

Diarrhoea (VIP production) | Cushings (ACTH production)

How is a medullary carcinoma treated?

Total thyriodectomy

What are good prognostic factors in medullary carcinoma?

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

What suggests an aggressive tumour in a medullary carcinoma?

Necrosis Many mitoses Small cell morphology

What is an anaplastic carcinoma?

Undifferentiated and aggressive tumour

Who is an anaplastic carcinoma likely to affect?

Usually older patients | In people with a history of differentiated thyroid cancer

What are the different scales for thyroid cytology?

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

What cells compose parathyroid cells?

Chief cells | Oxyphil cells - slightly larger cells with acidophilic cytoplasm

What does the parathyroid group do?

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

What is the commonest pathology of hyperparathyrodism?

Small adenomas

What can hyperplasia of the parathyroid gland be associated with?

MEN 1 | MEN 2a

What causes secondary hyperparathyroidism?

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

What causes tertiary hyperparathyroidism?

Parathyroid activity becomes autonomous | Associated with hypercalcamia

What can hyperparathyroidism cause?

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)

When can you get hypoparathyroid?

Post-op | Di George 22q11.2

What are the sympoms of hypoparathyroidism?

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