4. Hypothyroidism Flashcards
where is negative feedback from the thyroid gland going to?
hypothalamus and pituitary gland
what does primary hypothyroidism result in?
less T4 in circulation - a lot of TRH and TSH is produced
how is primary hypothyroidism tested for?
test for high TSH in the blood because TRH is undetectable
what is the composition of the thyroid gland?
colloid full of stored thyroxine surrounded by follicular cells which make the thyroxine
what happens after the pituitary makes TSH?
iodide is pumped into the follicular cells, it is oxidised to iodine and is then made into monoiodotyrosine which is stored in the colloid
when needed, the pituitary sends signals to thyroid proteolytic enzymes to stimulate the release of thyroxine into the circulation which controls the basal metabolic rate
what is primary hypothyroidism (myxoedema) and what is it caused by?
autoimmune damage to the thyroid or thyroidectomy which results in a decline of thyroxine levels
TSH levels rise to try and stimulate thyroxine production but eventually TSH levels will fall as it becomes exhausted
what are the features of primary hypothyroidism?
EVERYTHING SLOWS DOWN
- deepening voice
- depression and tiredness
- cold intolerance
- weight gain and reduced appetite
- constipation
- bradycardia (pulse rate 50bpm)
- heart enlargement
- amenorrhoea
- eventual myxoedema coma
what is thyroxine (T4) converted to and by what?
deiodinase enyme converts it to the more active metabolite T3
what is the treatment of hypothyroidism?
thyroxine daily - one 100mg tablet
monitor TSH and adjust the dose until TSH is normal
how does T3 produce a cellular response and biological effect?
T3 travels to the nucleus and combines with a heterodimer made up of thyroid receptor and the retinoid x receptor
the 3 molecules bound together bind to a part of the DNA called the thyroid response element
what is the drug of choice in thyroid hormone replacement therapy?
T4 (thyroxine) is normally given as a salt of thyroxine - levothyroxine sodium
sometimes T3 is given because it is more biologically active, liothyronine sodium (salt of T3) is less commonly used
what are the clinical uses of levothyroxine sodium (synthetic tyroxine)?
- primary hypothyroidism - oral administration, TSH is used as a guidance for thyroxine dose as we aim to suppress TSH into the reference range
- secondary hypothyroidism - oral administration, TSH is low due to anterior pituitary failure so cant be used as guidance, free T4 is used as guidance instead
what is the clinical use of liothyronine (synthetic T3)?
myxoedema coma - T3 is faster acting
given intravenously initially and then oral when possible
what is combined thyroid hormone replacement?
combination of T3 and T4 is given because there is some reported improvement in well being
what are the risks of T3 in treatment?
T3 is very potent and combination therapy can be complicated by symptoms of toxicity: palpitations, tremor, anxiety
