Pathology of the thyroid Flashcards
What level does the thyroid sit at?
C5/6 - T1
How heavy is the thyroid gland?
15-25g
How does the thyroid develop embryologically?
Evagination of pharyngeal epithelium
Descent from foramen caecum to normal location along thyroglossal duct
What can cause a lingual thyroid?
Failure of descent
What can cause a retrosternal location thyroid in the mediastinum?
Excessive descent
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)
What do C cells secrete?
Calcitonin
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
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
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
What does cAMP do in the follicular cells?
It increases the production and release of T3 and T4
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
What can an enlargement of the thyroid gland present as?
Mass effect - stridor, dysphagia
What autoimmune disease causes hypothyrodism?
Hashimoto’s thyroditis
What autoimmune disease causes hyperthyrodism?
Grave’s disease
What polymorphisms are present in hashimoto’s thyroditis?
CTLA-4 - negative regulator of T cell responses,
PTPN-22 - inhibitis T cell response
What are the other causes outwith autoimmune diseases that cause thyroid problems?
Infection Palpation Subactue lymphocytic de Quervian's Ridel's
What will the thyroid gland be like in Ridel’s?
Associated with fibrosis with a hrad/craggy gland that mimics a malignancy
What can cause hyperthyrodism?
85% grave's Hyperfunctioning nodules and tumours TSH secreting pituitary adenoma Thyroditis Ectopic production (stuma ovarii) Factitious (exogenous intake)
Who is grave’s disease likely to affect?
10F:1M
20-40 years oldd
What antibodies will be present in grave’s disease?
Anti-TSH - thyroid stimulating immunoglobulin
What is the triad of features associated with grave’s disease?
Hyperthyrodism with diffuse enlargement of the thyroid
Eye changes
Pretibial myoxdema
What does grave’s disease look like histologically?
Many lymphoid cells
Thyroid follicles that lack colloid
Colloid scalloping
What is hypothyrodism?
Symptoms and signs due to low levels of T3 and T4
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