Thyroid

Question 1

How does iodine enter the thyroid follicular cell?

Answer 1

From the blood, via an iodine/sodium symporter

Question 2

How does iodine enter the follicle colloid?

Answer 2

It diffuses across the thyroid follicular cell and enters to colloid through the Pendrin transporter

Question 3

Once in the colloid, how are thyroid hormones formed from iodine?

Answer 3

Iodide is oxidised to iodine
Iodine then combines with thyroglobulin via the action of thyroid peroxidase, to produce MIT and DIT
- mono/di-iodinated tyrosine
MIT and DIT thyroglobulin are then endocytosed into the cell
Proteolysis occurs to breakdown the thyroglobulin
MIT and DIT = T3
DIT and DIT = T4

Question 4

In what form are thyroid hormones normally secreted?

Answer 4

Pro-hormone (T4)

T3 is the active hormone and is secreted in very low quantities

Question 5

If T3 is the active hormone, why is T4 secreted in larger quantities from the thyroid gland?

Answer 5

T4 is converted to T3 by peripheral 5’-deiodination

T3 is very unstable and acts quickly so can’t be circulated

Question 6

What are the functions of the thyroid hormones?

Answer 6

Negative feedback on TRH and TSH
Increased metabolism
Growth and development
Increased catecholamine effect

Question 7

What are the normal thyroid hormone concentrations in the blood?

Answer 7

Free T4 (used in diagnostic testing) - 9-21pmol/l
Total T4 - 60-160nmol/l
Free T3 - 0.9-2.5pmol/l
Total T3 - 1.2-2.6nmol/l

Question 8

What is the medical treatment for hypothyroidism?

Answer 8

Levothyroxine - synthetic T4 75-150mcg per day

Question 9

Name some of the causes of hypothyroidism,

Answer 9

Thyroidectomy 
Post radioactive iodine ablation
Autoimmune
- thyroiditis
- silent
- Hashimoto's
Blocking TSH receptor antibodies 
Congenital hypothyroidism 
Hypopituitarism

Question 10

What happens to babies if the mother has hypothyroid disease?

Answer 10

Neonatal hypothyroidism

• cretinism
• coarse facial features
• macroglossia
• umbilical hernia
• mottled, cool and drug skin
• developmental delay
• pallor
• myxoedema
• goiter

Question 11

What are the most common causes of congenital hypothyroidism?

Answer 11

Thyroid dysgenesis
- TSH receptor 
Dyshormonogenesis 
- thyroid peroxidase 
- thyroglobulin
- sodium/iodide symporter
- pendrin (pendred syndrome)

Question 12

What investigations would you perform on someone with suspected hyperthyroidism?

Answer 12

TSH
Free T4
Free T3
TSH receptor antibodies 
TPO - thyroid peroxisomal antibody 
123 I uptake scan - radiolabelled iodine

Question 13

What is the treatment for hyperthyroidism?

Answer 13

Beta blockers - symptom management 
Carbimazole 
- prodrug of methimazole 
- prevents iodination of thyroglobulin (prevents coupling of thyroid peroxidase enzyme)
Propylothiouracil
131 I - radioactive iodine 
Thyroidectomy

Question 14

Describe the aetiology of Graves Disease.

Answer 14

Autoimmune disease - associated diseases in family
Genetic suscpetibility (HLA, TG and thyroid receptor)
Environmental - iodine, tobacco smoke
Immune modulating treatment - IFN, alemtuzemab

Question 15

Name some causes of hyperthyroidism.

Answer 15

Pituitary adenoma
Other hormones acting as TSH - HcG
Autoimmune 
- thyroiditis acute early phase
- activating TSH receptor antibodies 
Thyroid adenoma

Question 16

How does amiodarone affect the thyroid?

Answer 16

200mg of amiodarone releases 6mg of iodine

Question 17

Name the types of amiodarone thyroid disease.

Answer 17

Type 1
- autoimmune thyrotoxicosis
- treated with high dose carbimazole 
Type 2
- destructive thyroiditis 
- treated with glucocorticoids

Question 18

What are the effects of oral contraceptive pill on thyroid function?

Answer 18

It increases the amount of binding proteins available

- the level of total T4 increases

Question 19

What are the different types of tumour that can occur in the thyroid gland?

Answer 19

Follicular cell
- papillary cancer
- follicular cancer
- anaplastic cancer
- poorly differentiated 
Thyroid C cell
- medullar cancer

Question 20

How are thyroid carcinomas diagnosed?

Answer 20

Fine needle aspirate of nodules

Question 21

How are thyroid carcinomas treated?

Answer 21

Surgical removal
Therapeutic radioiodine 
TSH suppression (papillary cancers depend on TSH stimulation for growth)
Monitor thyroglobulin 
Multikinase inhibitors

Question 22

Name some diseases related to mutation of RET protooncogene.

Answer 22

Familial medullary thyroid cancer
Multiple endocrine neoplasia type 2 and 3
Hirschprungs

Question 23

What is thyroid eye disease?

Answer 23

Muscles and soft tissues of the eye socket swell

- associated with problems with thyroid gland (commonly overactive, but can occur in both)