Hypothyroidism Flashcards
Where and how does TSH act specifically?
It switches on follicular cells of the thyroid gland and release thyroxine into the bloodstream
What does thyroxine do?
Keeps basal metabolic rate high and body temperature constant
What is the most common cause of thyroid gland failure (primary hypothyroidism)?
Autoimmune disease of the thyroid
What percentage of the population will be affected by thyroid gland failure?
5%
Explain the biochemistry of primary hypothyroidism?
There is a fall in the level of the thyroxine- feel cold and tired
Pituitary detects fall and produces loads of TSH to compensate
What are some common signs and symptoms of primary hypothyroidism?
Tongue gets thick Speech slows down Deepening of voice BMR falls Bradycardia General weakness Depression Cold intolerance Weight gain and reduced appetite Constipation
What are the two hormones that a healthy thyroid secretes?
T3 and T4
Explain the relationship between T3 and T4?
T4 (thyroxine) is a pro-hormone that is converted to active T3 by deiodinase
How is the majority of T3 in the circulation formed?
80% from the conversion of T4
20% from direct thyroidal secretion
Describe the relationship between T3 and T4 in terms of thyroid hormone activity at target cells?
T3 provides almost all of the thyroid hormone activity
Where is thyroxine converted to T3 by deiodinase?
In the target cell
Where does T3 go once inside the target cell?
To the nucleus where it binds to the thyroid hormone receptor
What happens after T3 has bound to thyroid hormone receptor?
The THR then heterodimerises with the retinoid x receptor. This complex then binds to the thyroid response element that causes a change in gene expression
What is usually used as thyroxine replacement?
Levothyroxine sodium
What is used as the guideline for thyroxine dose in primary?
TSH levels as it suppresses TSH by negative feedback
Where is the problem in secondary hypothyroidism?
Pituitary gland
What is used to treat secondary hypothyroidism?
Levothyroxine sodium
What is used as the guideline for thyroxine dose in secondary?
They don’t produce TSH so this can’t be used, free T4 levels are used instead
What is liothyronine sodium (T3) used for?
Myxoedema coma - very rare complication of hypothyroidism
I.V liothyronine is given as its onset is faster than T4
What are the complications of T3 treatment?
Switch off TSH and patients may complain of symptoms of thyrotoxicosis:
palpitations, tremor and anxiety
What are some adverse effects of thyroid hormone over-replacement?
Usually associated with low TSH Skeletal- Increased bone turnover Reduction in bone mineral density Risk of osteoporosis Cardiac- Tachycardia Risk of dysrrythmia Metabolism- Increased energy expenditure Weight loss Increased beta-adrenergic sensitivity- Tremor Nervousness
How do T4 and T3 normally exist in circulation?
Highly bound- 99.97% of circulating T4 and 99.7% of T3 are plasma protein bound
Which plasma protein is T3 and T4 mainly bound to?
Thyroxine binding globulin
When do plasma proteins increase?
Pregnancy and on prolonged treatment with oestrogen and phenothiazides
When do plasma proteins decrease?
If you have liver disease or are severely malnourished
In terms of quantity in the plasma, how do T3 an T4 compare?
10 times more T4 in plasma than T3
How is T3 and T4 cleared?
Free and conjugated hormone is secreted into bile and urine:
T3 is cleared in hours
T4 is cleared in about 6 days
