ChemPath 9: Thyroid

Question 1

What controls the uptake of iodine by thyroid follicular cells in the thyroid gland? where is this made?

Answer 1

TSH from the pituitary gland

Question 2

What needs to be done to iodine that is taken up in the GIT?

Answer 2

Needs to be converted to iodide as this is what is taken up by thyroid gland

Question 3

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

Answer 3

Iodide is actively taken up into thyrocytes via a Na+/K+/ATPase pump

Question 4

How is thyroxine produced?

Answer 4

Thyroglobulin = protein in thyroid gland

Iodide that has been taken up is converted to iodine via thyroid peroxidase

Iodine + thyroglobulin -> MIT, DIT and eventually T3 and T4

Question 5

Where is thyroxine stored once produced?

Answer 5

Once thyroxine (T4) is produced, it is stored inside the thyroid gland colloid

Question 6

What percentage of thyroxine is free active T4?

Answer 6

0.03%

Question 7

What does thyroxine bind to in the blood?

Which is main + when might it be low?

Answer 7

Thyroxine binding globulin (TBG) - 75% = MAIN (based on albumin synthesis hence if albumin is low -> TBG low)

Thyroxine-binding prealbumin (TBPA) = 20%

Albumin = 5%

Question 8

Outline the hypothalamo-pituitary-thyroid axis

Answer 8

The hypothalamus produces TRH (thyrotrophin releasing hormone) which stimulates the release of TSH (thyroid stimulating hormone) from the anterior pituitary

TSH stimulates T3/T4 production

T4 feeds back to the hypothalamus and pituitary
(Good image on notion)

Question 9

List some causes of hypothyroidism.

Answer 9

Hashimoto’s thyroiditis (autoimmune) = MOST COMMON CAUSE

Postpartum-thyroiditis

Atrophic thyroid gland

Iodine deficiency (CAUSE IN DEVELOPING WORLD)

Pituitary disease

Peripheral thyroid hormone resistance

Post-Graves’ disease (after treatment)

Drugs (e.g. amiodarone, lithium)

Question 10

Outline the investigation findings that may be seen in hypothyroidism.

Answer 10

High TSH + Low T4 = Primary hypothyroid

Thyroid peroxidase antibodies (suggests autoimmune)

Look out for other autoimmune conditions (eg. pernicious anaemia, coelic and addisons)

Question 11

Why do ECG in patients with suspected hyopothyroidism?

What should you do?

Answer 11

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 12

How is hypothyroidism treated?

Risk of overtreatment?

Answer 12

Levothyroxine (T4 - 50-125-200 µg/day titrated to a normal TSH)

Overtreatment can cause osteopaenia & AF

Patients may want to take too much as it can help them lose weight

Question 13

What is subclinical hypothyroidism? AKA?

When might these pts be more likely to develop 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

How does 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? - What component is tested for?

What is the timing and why?

Answer 16

Guthrie test - Looking at TSH

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

Question 17

What happens if neonatal hypothyroid is tested too early / too late?

Answer 17

Too early = ridiculously high due to maternal TSH

Too late = untreated hypothyroidism which can lead to intellectaual problems in later life

Question 18

What is sick euthyroid?

Answer 18

Alteration in the pituitary thyroid axis in non-thyroidal illness (can happen in any severe illness)

In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate

Question 19

Biochemical findings in sick euthyroid?

Answer 19

Low T4 and T3
Normal/high TSH

NOTE: these patients do not have symptoms of hypothyroidism + giving thyroxine will not improve their symptoms

Question 20

What are the three main causes of hyperthyroidism?

Others?

Answer 20

1. Graves’ disease (40-60%)
2. Toxic multinodular goitre / Plummers disease (30-50%)
3. Single toxic adenoma (5%)

Others: subacute thyroiditis, post-partum thyroiditis,

Question 21

What is post-partum thyroiditis?

Answer 21

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

After the child is born, the thyroid gland is attacked by these antibodies - → hyperthyroidism as stored thyroid hormone is released

Thyroid hormone stores used up → patient becomes hypothyroid → patient becomes euthyroid

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

TFTs = Low TSH, High T4 and T3

Thyroid antibodies (thyroid microsomal antibodies =anti-TSH) - seen in graves

Technetium scan

Question 24

What is a technetium scan used for in thyroid disease?

Causes of high / low uptake?

Answer 24

A Technetium scan can be used to see which parts of the thyroid are producing excessive thyroid hormone

High:

• Grave’s
• Toxic multinodular goitre
• Single toxic adenoma

Low:

• Subacute thyroiditis
• Post-partum thyroiditis

Question 25

Mx of hyperthyroidism?

Answer 25

Symptomatic:
B-blocker - tachycardia
ECG - ensure no fast AF
DEXA / bone mineral density scan - exclude osteoporosis / osteopaenia

Thionamides (Carbimazole, propylthiouracil) - can reduce T3 and T4 production

Radioiodine + surgical removal of gland - if persistently high despite thionamide use

Question 26

What is a major risk of radioiodine treatment for hyperthyroidism?

Answer 26

Can precipitate thyroid storm (release of thyroxine from gland)

Can result in hypothyroidism

Question 27

Features of Graves disease?

Why is there a need to be careful of radioiodine use?

Answer 27

Diffuse goitre
Thyroid-associated ophthalmopathy
Pretibial myxoedema
Thyroid acropachy - skeletal abnormality

NOTE: radioiodine can make Graves’ eye disease worse

Question 28

MoA of thionamides?

Examples?

Answer 28

Prevents the conversion of iodide to iodine by thyroid peroxidase

Carbimazole, propylthiouracil

Question 29

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

Mx re this?

Answer 29

Agranulocytosis

Patients should be advised to stop treatment if they develop a sore throat or fever

Question 30

What kind of dosing regimes can be used for thionamides?

Answer 30

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 31

Which drug can be given to hyperthyroid patients prior to surgery?

Why is this given?

Answer 31

Potassium perchlorate

To prevent uptake of iodine into thyroid cells

Question 32

What are the different types of thyroiditis?

Answer 32

Subacute / viral thyroiditis / De Quervains thyroiditis

Post-partum thyroiditis

Silent thyroiditis - immune and amiodarone caused

Question 33

Pathophysiology of Subacute/ viral thyroiditis/ De Quervain’s Thyroiditis?

Answer 33

This is where someone has a thyroid illness

Virus attacks the thyroid gland → patient first presents with hyperthyroidism as stored thyroid hormone is released

Thyroid hormone stores used up → patient becomes hypothyroid

Once virus clears → patient becomes euthyroid

Question 34

What is the long-term treatment of thyroiditis?

Answer 34

Thyroxine replacement

Question 35

What are the two most common forms of thyroid cancer?

Tumour marker + what is this used for

Answer 35

Differentiated thyroid carcinoma:

• Papillary thyroid cancer
• Follicular thyroid cancer

Thyroglobulin - monitoring relapse following mx

Question 36

What is a rare but devastating thyroid cancer?

Which cells do they arise form? What condition can this be part of?

Answer 36

Medullary Thyroid Carcinoma

Calcitoning-producing C cells of the thyroid gland

Can be part of MEN2

Question 37

Mx of Differentiated thyroid carcinoma?

What can be given as adjuncts?

Answer 37

Total thyroidectomy

radioiodine treatment may also be given

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

Question 38

Name two tumour markers used for medullary thyroid cancer?

Answer 38

Calcitonin

CEA

Question 39

Try cases on the notion

Answer 39

OKAY!