Thyroid function and dysfunction

Question 1

Which two hormones are released by the thyroid?

Answer 1

T3 and T4

Question 2

How does hypothalamus communicate with anterior pituitary?

Answer 2

TRH

Question 3

How does anterior pituitary communicate with thyroid?

Answer 3

TSH

Question 4

Which two compounds form basis of T3 and T4?

Answer 4

Tyrosine and iodine

Question 5

What does colloid do?

Answer 5

Production of T3/T4

Question 6

How are T3/T4 made?

Answer 6

Thyroglobulin made from follicular cells
I- and Na+ move into cell (co-transport)
I- trapped
TPO converts to iodine by H2O2
Binds to tyrosine 
Forms MIT and DIT
2x DIT makes T4
DIT and MIT makes T3

Question 7

What does pendrin do?

Answer 7

Pushes iodine into colloid

Question 8

What does thyroid hormone do?

Answer 8

Increases metabolic activity

Activates via DNA transcription

Question 9

Half life of T3

Answer 9

1 day

Question 10

Half life of T4

Answer 10

7 days

Question 11

Why is more T4 made than T3?

Answer 11

T4 converted to T3

Question 12

What does TSH do to make T3 and T4?

Answer 12

Stimulates symporter, thyroglobulin synthesis and exocytosis

Question 13

Thyroid impact on gene expression in nucleus

Answer 13

Stimulates nuclear receptors to activate DNA transcription, receptors are normally occupied by inhibitory repressors which are displaced by T3 to start activation

Question 14

Thyroid impact on gene expression in mitochondria

Answer 14

Direct action to increase oxidative phosphorylation, stimulates mitochondrial DNA transcription

Question 15

Thyroid impact on cell membrane in mitochondria

Answer 15

GPCR (Gq) = stimulates nuclear DNA transcription

Question 16

Action of thyroid hormones

Answer 16

Enhances basal metabolic rate 
Increases cardiac muscle activity 
Increases Sympathetic NS activity 
Protein synthesis
Activates GH

Question 17

Symptoms of hypothyroidism

Answer 17

• Weight gain
• Under-active thyroid:
• Slowed metabolic rate, reduced oxygen consumption, reduced protein synthesis
• Symptoms:
• Lethargy
• Weight gain
• Cold intolerance
• Bradycardia/hypotension
• Slow reflexes and speech
• Dry skin/thinning hair
• Mucopolysaccharide deposits (myxoedema)
• Adult screening not done routinely
• Outer third of eyebrow lost

Question 18

TSH, T3 and T4 for hypothyroidism

Answer 18

TSH increased, T3 and T4 decreased

Question 19

Causes of underachieve thyroid

Answer 19

Surgery
Anterior pituitary damage - tumour/surgery
Autoimmune - Hashimoto
Iodine deficiency

Question 20

What is Hashimoto’s disease?

Answer 20

Normal immune tolerance falls
CD4+ lymphocytes recruit B cells and CD8+ cells to thyroid
Anti-TPO ABs and anti-thyroid cytotoxic T cells result in follicular destruction

Question 21

Causes of congenital hypothyroidism

Answer 21

Iodine deficiency
Developmental failure
Genetic defects

Question 22

Symptoms of congenital hypothyroidism

Answer 22

Coarse appearance, floppy, mental retardation, short stature

Question 23

Symptoms of hyperthyroidism

Answer 23

Weight loss, heat intolerance, tremor, tachycardia, muscle weakness

Question 24

What is exophthalmos?

Answer 24

Inflammation behind eyes

Question 25

Causes of hyperthyroidism

Answer 25

TSH secreting tumour on ant. pituitary Autoimmune (Grave's or early Hashimoto) Adenomas

Question 26

What is Grave's disease?

Answer 26

Normal immune balance disrupted, anti-TSH receptor ABs generated that mimic TSH and stimulate receptor by binding to it

Question 27

Summary of Hashimoto

Answer 27

Anti TPO antibodies Impaired thyroid hormone synthesis Hypothyroidism Low T3/4 and high TSH

Question 28

Summary of Grave's disease

Answer 28

Anti TSH receptor Binds to receptor and mimics TSH Hyperthyroidism High T3/4, low TSH

Question 29

Papillary thyroid cancer

Answer 29

Affects papillary cells Slow growing Spread to lymph nodes Good outcome

Question 30

Follicular thyroid cancer

Answer 30

Affects follicle cells Spreads to lungs/bones Good outcome with surgery and iodine

Question 31

Medullary thyroid cancer

Answer 31

``` Affects c cells (calcitonin) Aggressive Distant spread Radical surgery needed Fair outcome ```

Question 32

Anaplastic thyroid cancer

Answer 32

``` Affects undifferentiated cells Very aggressive Invades airway Treatments are minimally effective Poor outcome ```