Hypothyroidism Flashcards
thyroxine store in thyroid
there is enough thyroxine stored in the colloid for a month
what happens in the colloid?
Iodide ions in the presence of TPO and H2O2, are converted to a reactive iodine form.
[2] I* then iodinates one (MIT) or two (DIT) positions on TG to create mono-iodotyrosines (MIT) or di-iodotyrosines (DIT) – Both are forms of TG.
[3] TPO and H2O2 then catalyse a coupling reaction to create tri-iodothyronines (T3) or tetra-iodothyronines (T4) – Again, forms of TG.
[4] Lysosomes then uptake clumps of colloid which is broken down to liberate T3 and T4 moves to the blood.
what causes primary hypothyroidism/myxoedema?
autoimmune damage to the thyroid
what are the plasma levels of TSH and thyroxine in primary?
high level of TSH
low levels of T4
symptoms of hypothyroidism
- deepening of voice
- bradycardia
- weight gain
- decreased appetite
- cold intolerance
- low BMR
- constipation
- depression
- tiredness
- eventual myxoedema coma
T4
tetraiodothyronine - prohormone
converted into the bioactive T3 form within tissue by deiodinase activity
circulation of T3
80% made from the deionisation of T4
20% made from direct secretion from thyroid
T3
all activity is caused by T3 (BIOACTIVE)
- travels into nucleus
- binds to heterodimer of TR and RXR
- bonds to TRE (thyroid response element)
what thyroxine is given in hormone replace therapy
T4 (over T3) so the body can actively convert it to T3
what form is the thyroxine given in, in therapy?
Levothyroxine sodium
what cases is Levothyroxine given in ?
1) autoimmune primary
2) iatrogenic e.g. post thyroidectomy
3) secondary e.g. pit. tumour
administration of Levothyroxine
oral form
dosage based on TSH level
aim is the suppress TSH into normal parameters
problem of finding correct dosage in secondary hypothyroidism
TSH is low due to the failure of the pituitary
oral form is given but TSH is not used as the guide
aim to move fT4 into the middle of the reference range
combination therapy
reported improvement in well being when T3 and T4 are given together
problem with combined therapy
T3 is very potent and has a toxicity effect causing palpitations, tremors and anxiety
it feels like having excess thyroxine
what are the adverse effect of over replacement of thyroid hormones
skeletal- increased bone turnover, reduction in bone density (osteoporosis)
cardiac- tachycardia, risk of dysrhythmia, atrial fibrillation
metabolism- increased energy expenditure, weight loss
increased beta-adrenergic activity- tremor, nervousness
pharmokinetics of drugs levothyroxine and liothyronine
orally active
T3 drug
liothyronine sodium
less common, used for rapid effect in a myxoedema coma due to potency
IV administration
half life of levothyroxine
6 days
half life of liothryonine
2.5 days
binding of T4 and T3 to plasma proteins
T4 is 99.97% bound
T3 is 99.7% bound
mainly to thyroxine Binding Globulin
changes in TBG : increase
increase in pregnancy
during prolonged treatment with oestrogen and phenothiazines
changes in TBG: fall
with malnutrition
liver disease
certain drug treatments e.g. co-administered drugs phenytoin and salicylate compete for PPB binding sites
relative numbers of T4 and T3 in plasma
10x more T4 than T3
clearance of T4 and T3
T3 cleared in hours (active form needs quick remove)
T4 cleared in 6 days (inactive form to be used)
what would a blood test for hypothyroidism show?
low thyroxine
high TSH
give an example of secondary hypothyroidism
Sheehan’s syndrome
the pituitary is affected due to post-partum haemorrhage
