ChemPath: Thyroid

Question 1

What controls the uptake of iodine by thyroid follicular cells?

Answer 1

TSH

Question 2

Which channel is important for the transport of iodine across the cell membrane?

Answer 2

Na+/K+ ATPase

Question 3

Which enzyme converts iodide to iodine?

Answer 3

Thyroid peroxidase

Question 4

How is thyroxine produced?

Answer 4

Iodination of tyrosine residues in thyroglobulin generates MIT and DIT which leads to the formation T3 and T4

Question 5

what percentage of thyroxine is free active T4?

Answer 5

0.03%

Question 6

What does thyroxine bind to in the blood?

Answer 6

• Thyroxine binding globulin (TBG)
• Thyroxine-binding prealbumin (TBPA)
• Albumin

Question 7

Outline the hypothalamo-pituitary-thyroid axis.

Answer 7

• The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
• TSH stimulates T3/T4 production
• T4 feeds back to the hypothalamus and pituitary

Question 8

List some causes of hypothyroidism.

Answer 8

• Hashimoto’s thyroiditis (autoimmune)
• Atrophic thyroid gland
• Post-Graves’ disease (after treatment)
• Post-thyroiditis
• Drugs (e.g. amiodarone, lithium)
• Iodine deficiency
• Pituitary disease
• Peripheral thyroid hormone resistance

Question 9

Outline the investigation findings that may be seen in hypothyroidism.

Answer 9

• High TSH
• Low T4
• Thyroid peroxidase antibodies
• Look out for other autoimmune conditions

Question 10

Why is it important to do an ECG in patients with suspected hypothryoidism?

Answer 10

If someone with hypothyroidism has underlying cardiovascular disease, giving them thyroxine may induce ischaemia

NOTE: so you would start on a low dose of thyroxine and then escalate

Question 11

How is hypothyroidism treated?

Answer 11

Thyroxine (50-150-200 µg/day titrated to a normal TSH)

Question 12

What are some risks of overtreatment with thyroxine?

Answer 12

• Osteopaenia
• Atrial fibrillation

Question 13

What is a subclinical hypothyroidism?

Answer 13

• Normal T4 with high TSH
• Sometimes referred to as compensated hypothyroidism

NOTE: if TPO antibodies are positive, the patient may go on to develop hypothyroidism

Question 14

Why might there be some benefit to treating subclinical hypothyroidism?

Answer 14

• Hypothyroidism is associated with hypercholesterolaemia

Question 15

Outline how thyroid function changes in pregnancy.

Answer 15

• hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism
• Free T4 levels rise slightly
• TBG level increase dramatically

NOTE: hCG level drops later on in pregnancy

Question 16

How is neonatal hypothyroidism diagnosed?

Answer 16

Guthrie test

Question 17

Why is the timing of the Guthrie test important?

Answer 17

It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby

Question 18

What is sick euthyroid?

Answer 18

• Alteration in the pituitary thyroid axis in non-thyroidal illness
• In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate

Question 19

What are the TFT findings in sick euthyroid?

Answer 19

• Low T4 and T3
• Normal/high TSH

NOTE: these patients do not have symptoms of hypothyroidism

Question 20

What are the three main causes of hyperthyroidism?

Answer 20

• Graves’ disease
• Toxic multinodular goitre
• Single toxic adenoma

Others: subacute thyroiditis, post-partum thyroiditis

Question 21

What is post-partum thyroiditis?

Answer 21

During pregnancy, the body may produce antibodies that stimulat the thyroid gland

Question 22

What is struma ovarii?

Answer 22

A rare form of ovarian tumour (usually a teratoma) that contains mostly thyroid tissue and produces thyroxine

Question 23

List some investigation findings of hyperthyroidism.

Answer 23

• Low TSH
• High T4 and T3
• Technetium scan
• Thyroid antibodies (thyroid microsomal)

Question 24

Outline the management of hyperthyroidism.

Answer 24

• Beta-blocker
• ECG
• Bone mineral density
• Radioiodine
• Thionamides

Question 25

What is a major risk of radioiodine treatment for hyperthyroidism?

Answer 25

• Can precipitate thyroid storm
• Can result in hypothyroidism

Question 26

List some features of Graves’ disease.

Answer 26

• Diffuse goitre
• Thyroid-associated ophthalmopathy
• Pretibial myxoedema
• Thyroid acropachy

NOTE: radioiodine can make Graves’ eye disease worse

Question 27

What is the mechanism of action of thionamides?

Answer 27

Prevents the conversion of iodide to iodine by thyroid peroxidase

Question 28

What is a rare but important side-effect of thionamides?

Answer 28

Agranulocytosis

NOTE: patients should be advised to stop treatment if they develop a sore throat or fever

Question 29

What kind of dosing regimes can be used for thionamdes?

Answer 29

• Can be titrated to achieve normal T4 levels
• Block and replace - high dose is given to block the thyroid gland and then given thyroxine replacement

Question 30

Which drug can be given to hyperthyroid patients prior to surgery to block uptake of iodide?

Answer 30

Potassium perchlorate

Question 31

What is the long-term treatment of thyroiditis?

Answer 31

Thyroid hormone replacement

Question 32

What are the two most common forms of thyroid cancer?

Answer 32

• Papillary thyroid cancer
• Follicular thyroid cancer

Question 33

How is thyroid cancer treated?

Answer 33

• Total thyroidectomy

NOTE: radioiodine treatment may also be given

NOTE: high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining cells

Question 34

Which cells do medullary thyroid cancer arise from?

Answer 34

• Calcitonin-producing C cells

NOTE: it is part of MEN2

Question 35

Name two tumour markers used for medullary thyroid cancer?

Answer 35

Clacitonin

CEA