Hypothyroidism Flashcards
Where and how does TSH act specifically?
It switches on follicular cells of the thyroid gland and release thyroxine into the bloodstream
Controls uptake of i- which makes thyroxine stores
Controls enzyme that causes release of Thyroxine
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+Tiredness Cold intolerance Weight gain and reduced appetite Constipation Eventual myxoedema coma
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, located in nucleus, that causes a change in gene expression
What is usually used for primary hypothyroidism
-rimary hypothyroidism due to
Levothyroxine sodium–oral admin
-Autoimmune, iatrogenic-post thyroidectomy, post-radioactive iodine
What is used as the guideline for thyroxine dose in primary?
TSH levels as it suppresses TSH by negative feedback back into its reference range
Where is the problem in secondary hypothyroidism?
Pituitary gland– tumour, surgery, radiotherapy
What is used to treat secondary hypothyroidism?
Levothyroxine–oral admin
NOT LEVOTHYROXINE SODIUM – PRIMARY
What is used as the guideline for thyroxine dose in secondary?
They don’t produce TSH so this can’t be used, free T4 – active, not hormone bound levels are used instead
What is liothyronine sodium used for?
liothyronine sodium (T3)
Myxoedema coma - very rare complication of hypothyroidism
I.V liothyronine is given as its onset is faster than T4
What are the complications of combined T4T3 treatment?
Some reported improvement in well being
Switch off TSH and patients may complain of symptoms of thyrotoxicosis:
palpitations, tremor and anxiety
Pharmocokinetics how is T4 and T3 horm usually adminstered drug name
Comparison of half life
T4–Levothryoxine Sodium for primary hypothyroidism
Levothyroxine for secondary
both administered orally
T3 Liothyronine sodium administered as IV
T4- Plasma half life of 6 days
T3 plasma half life of 2.5 days
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
Thyroglobulin -glycoprotein in colloid in thyrofollicular cells that contain I2 and T3/T4
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
-Certain co-administered drugs e.g phenytoin, salicylates, compete for protein binding sites
