Hypothyroidism Flashcards
Draw the hypothalamo-pituitary-thyroid axis for regulation of T3/T4 production. (4)
Diagram on page 14. Marks:
- Hypothalamus produces TRH acts on thryotrophs in pituitary gland
- Release of TSH acts on thyroid gland
- Release of T3/T4 to act on peripheral tissues
- Negative feedback on hypothalamus and pituitary
What is the role of thyroxine binding globulin? (2)
- 99% of T3 and 99% of T4 bound to TBG in plasma
- Only free T3/T4 is available for action
- In pregnancy amount of TBG can go up
- In malnourished people/liver failure get reduced plasma TBG
Describe how TSH stimulates T3/TR production. (5)
- T3/T4 is made in follicles of thyroid gland
- TSH acts on basal membrane (TSHR)
- Ref to colloid/follicular cells
- Ref to Na/I symporter and thyroglobulin release into colloid
- Thyroid peroxidase catalyses oxidation of iodine and iodination of thyroglobulin (ref to MIT/DIT)
- TPO also catalyses coupling reaction to produce T3/T4
- Endocytosis at apical membrane + release of hormones consequently
What effect do T3/T4 have? (2)
- Alter gene expression
- Increase protein synthesis
- Increase BMR
What is the mechanism of action of T3/T4? (3)
- T3 is the predominant active form (T4 is deiodinated to T3 in cytoplasm of target tissues)
- T4 has longer half-life
- T3 binds to thyroid receptor (a nuclear receptor)
- Heterodimerisation with RXR (retinoid X receptor)
- Bind to HRE (thyroid response elements) on DNA to alter gene expression
State some of the clinical manifestations of hypothyroidism (primary myxoedema). (4)
- Reduced basal metabolic rate – everything slows down
- Cold intolerance
- Deep voice
- Weight gain
- Loss of appetite
- Depression
- Lethargy
- Speech slows down
- Bradycardia
- Constipation
What is primary myxoedema (aka primary hypothyroidism)? (2)
- It is a failure to produce T3/T4 due to failure of the thyroid gland
- Commonly due to autoimmune destruction of thyroid gland
- Characterised by low T3/T4 and high TSH
What is pituitary myxoedema (aka secondary hypothyroidism)? (2)
- This is actually a failure to produce sufficient TSH therefore leading to a deficit in T3/T4
- Commonly due to a pituitary tumour/post-pituitary surgery
How can primary myxoedema be distinguished from pituitary myxoedema? (2)
2 marks for a contrasting statement between the two:
- In primary myxoedema sometimes can get hypertension because get high amounts of vasoconstriction (compensatory for bradycardia). In pituitary myxoedema observe hypotension.
- In primary get heart enlargement. In pituitary myxoedema have a smaller heart
- In pituitary myxoedema do not observe the scaly skin and skin is less dry
- Could mention the difference in treatment: in primary myxoedema can use TSH to monitor dose. In pituitary myxoedema need to monitor plasma free T4 because TSH levels are low
How can hypothyroidism be treated? (2)
- Leveothyroxine (synthetic T4) = preferred choice
- Liothyronine sodium (T3) = less commonly used
- T4 is preferred because longer half-life therefore missing a dose is less problematic
Describe the levels of thyroxine and TSH in someone with primary thyroid failure. (1)
Need to get both:
Thyroxine = LOW
TSH = HIGH
What is the clinical use of liothyronine sodium? (2)
- Treatment of myxoedema coma (very rare complication of hypothyroidism)
- You give IV liothyronine sodium because the onset of action is faster than levothyroxine sodium
What is the problem with giving T3 replacement? (2)
- T3 is very potent so it is difficult to get the dose right
- Overdose can lead to adverse effects (thyrotoxicosis type symptoms): palpitations, tremor, anxiety
Describe some adverse effects of thyroid hormone over-replacement. (3)
Skeletal
Increased bone turnover
Reduced bone mineral density
Risk of osteoporosis
Metabolic
Increased energy expenditure
Weight loss
Cardiac
Tachycardia
Risk of dysrhythmia
Beta-adrenergic activity
Tremor
Nervousness
What factors can affect production of thryoxine binding globulins? (2)
1 from each section:
Increased by:
- Pregnancy
- Prolonged treatment with oestrogen and phenothiazines
Decreased by:
- Malnutrition
- Liver failure
