3. Hypothyroidism Flashcards
What is T4?
Tetraiodothyronine
Prohormone of T3, converted by deiodinase enzyme
What is T3?
Tri-iodothyronine
Source of all circulating T3?
80% - Deiodination of T4
20% - Directly secreted from thyroid
Mechanism of action of T3 in a cell?
T3 goes into nucleus, binds to thyroid hormone receptor, which is linked to a retinoid x receptor.
Both on Thyroid Response Element on chromosome.
Leads to altered gene expression
Treatment for primary/secondary hypothyroidism?
Levothyroxine (synthetic T4)
Half-life = 6 days
Treatment for myxoedema coma?
IV injection of Liothyronine (synthetic T3)
Half-life = 2.5 days
Pharmacokinetics of T3/T4?
99.7% plasma protein bound, mainly to Thyroxine-binding globulin (TBG)
When do PBPs increase?
During pregnancy
After prolonged treatment with oestrogens/phenothiazines
When do PBPs decrease?
Malnutrition
Liver disease
Drug interactions of levothyroxine/liothyronine?
Drugs that are heavily PBP bound can displace T3/T4, so can increase levels of free T3/T4 in blood.
e.g. Phenytoin, salicylates
How do you monitor levothyroxine treatment in primary hypothyroidism?
TSH will be HIGH in primary hypothyroidism.
T4 should have negative feedback on thyroid and LOWER the levels of TSH.
So if TSH levels go back to normal you are giving right dose.
How do you monitor levothyroxine treatment in secondary hypothyroidism?
TSH will be LOW in secondary hypothyroidism so cant use TSH levels to monitor
Therefore measure plasma FREE T4, aim for it to be in middle of reference T4 range.
Symptoms of hypothyroidism?
Deep voice Depression/tiredness Cold intolerance Weight gain + low appetite Constipation Bradycardia Eventual myxoedema coma
Limitations of using T3 as treatment?
Very expensive
No evidence to show it’s better than T4 treatment
