Goitre

Question 1

What is a goitre?

Answer 1

any enlargement of the thyroid gland: diffuse or multinodular

Question 2

What are the different causes behind a goitre?

Answer 2

• disorders most often due to a lack of dietary iodine or may be due to a lack of bio-availability of iodine
• reduced T3/T4 causes a rise in TSH production which stimulates gland enlargement
• may maintain a euthyroid state or if compensation fails have goitrous hypothyroidism

Question 3

there are two types of diffuse goitre - what are these?

Answer 3

endemic (>10% population) or sporadic

Question 4

What is the epidemiology of a sporadic goitre?

Answer 4

• F>M

- puberty and young adults

Question 5

what are the 3 aetiologies of a sporadic goitre?

Answer 5

• Ingestion of substances limiting T3/T4 production
• inborn error of metabolism
• in most cases cause is unknown

Question 6

How do sporadic diffuse goitres present? what is seen on TFTs? what can be seen in children?

Answer 6

usually euthyroid and present with mass effects
-T3/T4 normal but TSH usually high/upper limit of normal

-in children dyshormonogenesis may cause cretinism

Question 7

Multinodular goitre: what are the three different pathophysiologies of this?

Answer 7

Could be an evolution from a longstanding simple goitre:

• recurrant hyperplasia and involution
• enlargement can be large
• differential is thyroid neoplasm

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

Could be due to rupture of follicles, haemorrhage, scarring, calcification

Question 8

Adenoma and carcinoma are the different neoplasms that can be found in thyroid, what type of adenoma is found? what type of carcinomas occur?

Answer 8

Follicular adenoma

Carcinoma:

• papillary (75-85%)
• follicular (10-20%)
• Medullary (5%)
• anaplastic (<5%)

Question 9

what is a follicular adenoma? what are they composed of? What are these difficult to distinguish from? are they usually functional or non-functional? what can they sometimes secrete? what mutation do <20% follicular adenomas have?

Answer 9

This is a discrete solitary mass encapsulated by a surrounding collagen cuff
-composed of neoplastic thyroid follicles

can be difficult to distinguish from:

• dominant nodule in multinodular goitre
• follicular carcinoma
• usually non-functional
• can secrete thyroid hormones = thyrotoxicosis (in these adenomas there are mutations in the TSH receptor signalling pathways)
• <20% follicular adenomas have mutation RAS or P1K3CA

Question 10

Thyroid carcinomas: what is the epidemiology?

Answer 10

• female predominance

- early childhood

Question 11

what environmental aetiologies are assoc. with papillary carcinoma and follicular carcinoma?

Answer 11

Ionising radiation: papillary carcinoma

Iodine deficiency: follicular carcinoma

Question 12

What genetic aetiologies are assoc. with papillary, follicular, anaplastic and medullary thyroid carcinoma?

Answer 12

Papillary: RET, NTKR1, BRAF mutations
Follicular: P13k/AKT pathway mutations
Anaplastic: features of above, p53 and bcatenin mutations
medullary: MEN2

Question 13

Papillary thyroid carcinoma:

• is this common?
• what is the usual pathology?
• how can this present which is unlike follicular carcinoma?
• prognosis

Answer 13

Most common thyroid carcinoma

Pathology:

• usually solitary nodule in thyroid
• can be multifocal
• often cystic
• may be calcified

Some present with lymph node mets which is unlike follicular carcinoma

Overall good survival rate (95%+ at 10yrs) but worse if:

• > 40yrs old
• extrathyroid extension
• distant mets

Question 14

Follicular thyroid carcinoma:

• is this common?
• what is the usual pathology?
• how does this spread usually?
• what is the difference between a follicular adenoma and a follicular carcinoma?
• prognosis

Answer 14

2nd most common thyroid carcinoma

Pathology:

• usually single nodule
• slowly enlarging
• painless and non-functional

Haematogenous spread to bone, lungs, liver and rarely lymphatics

Need vascular or capsular invasion for a follicular adenoma to = carcinoma

Prognosis:
-depends on extent invasion/stage at presentation (higher = worse)

Question 15

Medullar carcinoma?

• is this common?
• what is the usual pathology?
• what are the three different types?
• What type of deposition is this assoc. with?

Answer 15

Rare
-derived from c-cells (can secrete calcitonin)

Sporadic (70%) or Familial or assoc. MEN2

Assoc. with amyloid deposition

Question 16

Sporadic medullary carcinoma:

• what age does this affect patients?
• what is the pathology usually?
• how do they behave usually?
• what can they cause clinically?

Answer 16

Assoc. with:
-40-50yrs

Pathology: usually a solitary nodule

Behave aggressively usually

Clinically:

• Neck mass with local effects: dysphagia, hoarseness, airway compromise
• paraneoplastic syndrome (VIP production causes diarrhoea, ACTH production causes cushings)

Question 17

Familial medullary carcinoma:

-what is the pathology?

Answer 17

Pathology:

• bilateral/multicentric
• c cell hyperplasia

Question 18

Anaplastic thyroid carcinoma:

• what is the pathology?
• who does this usually effect?
• how does the tumour behave?

Answer 18

Pathology: undifferentiated and aggressive tumour

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

this tumour grows rapidly and involves neck structures = death

Question 19

What is thyroid cytology? which lesions can be identified easily and which are more difficult to assess? what is the classification of thyroid cytology?

Answer 19

-Cells are studied from aspirates without architecture = minimally invasive assessment

• Papillary lesions can be identified from typical nuclear features
• follicular lesions difficult to assess as relation to capsule not assessed

Thy1 - insufficient/uninterpretable
Thy2 - benign
Thy3 - atypia prob. benign/equivocal
Thy4: atypia suspicious of malignancy
Thy5: malignant
(all follicular lesions graded as Thy3)