Week 9 Thyroid gland

Question 1

thyroid hormone examples:

Answer 1

T3 and T4
T4: Thyroxine
T3: tri-iodothyronine

Question 2

how are T3 and T4 made?

Answer 2

Tyrosine is iodinated to become T3 and T4.

Question 3

Thyroid hormone functions

Answer 3

1. thermogenesis in brown adipose tissue (BAT)
2. Basal metabolic rate
3. growth development
4. active mental processes

Question 4

HPT system: hypothalamus-pituitary-thyroid system

Answer 4

Hypothalamus: Thyrotrophin releasing hormone (TRH)
Pituitary: Thyroid stimulating hormone (TSH)
Thyroid: releases T3 and T4

T3 and T4 has -ve feedback loop to Hypothalamus and pituitary.

Question 5

T3 and T4 production ratio

Answer 5

Thyroid produces much more T4 than T3, T4:T3 is 14:1

Question 6

The compartments of Thyroid Follicle and C cell

Answer 6

Thyroid follicle:
- Inner compartment: colloid (glue-like)
- outer layers: thyroid epithelial cells and basement membrane
C cell: parafollicular

Question 7

What is the function of the colloid

Answer 7

The colloid makes T3 and T4!!

Question 8

What is the function of the C cell? (hint: c)

Answer 8

C cell produces calcitonin. (Very close to parathyroid!!!)
Calcitonin is made to reduce osteoclast activity and bone resorption.

Question 9

Thyroid hormone synthesis steps

Answer 9

1. Iodine is pumped from plasma into the colloid.
2. middle layer thyroid epithelial cells produces many thyroglobulin
3. The enzyme TPO with H2O2 can iodinate the tyrosine residues bound on thyroglobulin.
4. The colloid is reabsorbed into the epithelial cells.
5. Colloid undergoes proteolysis and degraded.
6. T3 and T4 are released from the colloid.

Question 10

What stimulates the release of T3 and T4 from the thyroid follicles?

Answer 10

TSH, TSH can stimulate Ca2+ influx which leads to secretion of T3/T4.

Question 11

What facilitates the process of iodinating tyrosine residues

Answer 11

the enzyme TPO and H2O2

Question 12

In what forms do Thyroid Hormones exist in circulation?

Answer 12

They are 99.5% bound to proteins like thyroxine binding globulins and albumin…
They ARE INACTIVE.

Question 13

What happens to T3/T4 when they get into cells?

Answer 13

• T4 gets converted to T3 through deiodinase 1/3
• T4 also gets converted to reverseT3 (rT3 - which is inactive) through deiodinase 1/2.
• T3 will bind to nuclear T3 receptors
  -»» changes

Question 14

Where does the majority of T3 production happen?

Answer 14

In liver, kidney cells, from the conversion of T4 to T3.

Question 15

Common causes of hyperthyroidism:

Answer 15

1. Graves Disease
2. Multi-nodular goitre
3. single toxic nodule

Question 16

Graves Disease cause

Answer 16

Stimulated by antibodies to the TSH receptor

Question 17

Graves Disease will lead to what symptoms?

Answer 17

Antibodies will stimulate T3 and T4 production.
Large smooth goitre
ophthalmopathy

Question 18

What’s a common imaging technique used in observing the thyroid gland

Answer 18

Radio-isotope uptake, technitium

Question 19

ophthalmopathy

Answer 19

TSH will stimulate the retro-orbital tissue which also has TSH receptor.
1. stimulation of fibroblasts
stimulate adipogeneis
stimulate ECM production
2. swelling of tissue behind the eye (lipid and water retention)

Question 20

Treatments of Graves Disease

Answer 20

1. Carbimazole
2. Radioiodine
3. Subtotal/total thyroidectomy
4. Beta blockers

Question 21

Carbimazole effect

Answer 21

• It is used to treat Graves disease
• It can inhibit TPO activity, which involved in T3/T4 synthesis.
• Decrease TSH receptor antibodies.

Question 22

Radioiodine effect

Answer 22

Used to treat Graves Disease:
Functions as negative feedback loop to hypothalamus and pituitary.

Question 23

Radioiodine complication

Answer 23

It could lead to hypothyroidism.
The negative feedback also doesn’t affect TSH receptor on ophthalmopathy, may worsen it.

Question 24

What can treat ophthalmopathy?

Answer 24

Steroids, immunosuppression, which can reduce inflammation.

Question 25

What does multi-nodular goitre do?

Answer 25

This is the patches of autonomous tissue that releases T3/T4 hormones. They also reduce growth of other parts of the thyroid gland.

Question 26

What is the usual treatment of multi-nodular goitre?

Answer 26

Radioiodine: iodine is taken up by thyroid cells, **radiation will kill thyroid tissues**. As it directly suppresses the thyroid tissue, it won't have a big issue with hypothyroidism

Question 27

Thyroiditis stages and need treatment?

Answer 27

**Hyperthyroidism** -> **hypothyroidism** due to follicule damage -> **euthyroid** (the thyroid has come back to normal)

Question 28

Weight in hypo/hyperthyroidism?

Answer 28

Weight loss in hyperthyroidism and gain in hypothyroidism. This occurs probably because thyroid hormones have control over metabolic rate and thermogenesis...

Question 29

Hypothyroidism causes

Answer 29

Most common cause: Hashimoto's thyroiditis Less common causes: Hypopituitarism (TSH dficiency), iodine deficiency, congenital...

Question 30

Mechanism of Hashimoto's thyroiditis

Answer 30

There are **autoimmune antibodies** that attack the thyroid gland that makes it underactive permanently. (Hereditary) **TSH levels may be high** due to underactive thyroid gland and low T3/4.

Question 31

Treatments of hypothyroidism

Answer 31

1. oral T4, to normalise TSH and T3 (increase T3 and reduce TSH) 2. some patients may require more direct T3 + T4 doses.

Question 32

What test measures thyroid hormone levels in thyroid disorders?

Answer 32

Immunoassays

Question 33

When is competitive immunoassay used?

Answer 33

Used for small molecules like thyroid/steroid hormones, drugs.

Question 34

How is competitive immunoassay done:

Answer 34

1. limited antibodies stuck on the wall 2. labelled analyte and sample that will **competitively bind to antibodies** 3. the more sample, the less labelled analyte. **Inversely proportional** to sample concentration.

Question 35

When is immunometric assay done?

Answer 35

For large molecules, peptide hormones (TSH, ACTH..) , proteins (BNP, troponin).

Question 36

What is tested in hyperthyroidism?

Answer 36

TSH receptor antibodies (they stimulate T3/4 production in the thyroid gland)

Question 36

How is immunometric immunoassay done:

Answer 36

1. excess antibodies (limitless) 2. The hormone will bind to the antibody 3. labelled antibodies will also bind to the hormone, but on **another epitope** 4. The stronger intensity, the more hormone concentration. **Directly proportional**

Question 37

What is tested in hypothyroidism

Answer 37

**Anti-TPO antibodies** (Autoimmune antibodies that attack the thyroid gland to make it underactive)

Question 38

Hypothyroidism biochemistry and cause

Answer 38

Low T3/T4 and high TSH: **primary** Low T3/T4 normal-low TSH: **hypopituitarism**

Question 39

Hyperthyroidism biochemistry and cause

Answer 39

**very low TSH**: primary Pituitary tumour (secondary): very rare, **high TSH**

Question 40

Sub-clinical hypothyroidism test

Answer 40

TSH **high sensitivity:** slight decrease in free T4: large increase in TSH

Question 41

Sub clinical hyperthyroidism test

Answer 41

slight increase in free T4, large decrease in TSH.

Question 42

How can thyroidal tests be affected?

Answer 42

Fluctuating TSH and T3/4 levels due to: - intercurrent illness.

Question 43

Stress, illness, malnutrition and thyroid hormones

Answer 43

- can all **negatively regulate the HPT axis** - **negatively regulate the nuclear T3 receptor**, and inhibit deiodinase 1/3 that's used for T4 conversion to T3.

Question 44

low TSH in a clinical setting

Answer 44

more likely to be non-thyroidal cause than hyperthyroidism

Question 45

raised TSH in a clinical setting

Answer 45

could be from recovery from illness.