hypothyroid disorders Flashcards
what does a healthy adult thyroid gland secrete?
both T4 and T3
what is T4?
Tetraiodothyronine (Thyroxine, T4)
= a prohormone
converted by deiodinase enzyme into the more active metabolite tri-iodothyronine (T3)
where does the circulating T3 come from?
Circulating T3
80% from deiodination of T4
20% from direct thyroidal secretion.
Is T4 or T3 more active?
T3 provides almost all the thyroid hormone activity in target cells.
what does T3 bind to?
it binds to the TRE (thyroid response element in the DNA) along with the RXR (retinoid x receptor) and TR (thyroid hormone receptor)
this leads to altered gene expression
what is used in thyroid hormone replacement therapy?
Levothyroxine sodium
thyroxine sodium; thyroxine;
Tetraiodothyronine; T4
usually the drug of choice
Liothyronine sodium
triiodothyronine; T3
- Less commonly used
what is primary hypothyroidism
what would you administer and check for?
Primary hypothyroidism eg autoimmune, iatrogenic - post-thyroidectomy, post-radioactive iodine – autoimmune damage to the thyroid. o Thyroxine (T4) levels low, TSH levels hig
LEVOTHYROXINE (synthetic thyroxine)
Oral administration
TSH used as guidance for thyroxine dose - aim to suppress TSH into the reference range
draw the system for how TRH, TSH and thyroxine works
see slide
what is secondary hypothyroidism?
what would you administer and check for?
Secondary hypothyroidism – eg pituitary tumour, post-pituitary surgery or radiotherapy
Oral administration of T4 TSH low due to anterior pituitary failure, so can’t use TSH as a guide to dose. Aim for fT4 middle of reference range
what is myxoedema coma?
Myxoedema coma - a VERY RARE complication of hypothyroidism
how should the LIOTHYRONINE (synthetic trio-iodothyronine) be administered?
iv initially – as onset of action faster than T4
then oral when possible
what are the pros of T4 intake than T3?
active orally
Half-life long
Levothyroxine (T4) plasma half life of 6 days
Liothyronine (T3) plasma half life 2.5 days
what type of thyroid hormone can the body use?
Approximately 99.97% of circulating T4 and 99.7% of circulating T3 are bound to plasma proteins, mainly thyroxine binding globulin (TBG) (NB do NOT confuse with thyroglobulin)
Only the free (unbound) fraction of thyroid hormone is available to the tissues
- plasma binding proteins increase in pregnancy and on prolonged treatment with oestrogens and phenothiazines - TBG falls with malnutrition, liver disease - certain co-administered drugs (e.g. phenytoin, salicylates) compete for protein binding sites.
what happens inside the colloid?
Inside the colloid – [1] 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 à moves to the blood.
symptoms of primary hypothyroidism
o Deepening voice. o Depression and tiredness. o Cold intolerance. o Weight gain, reduced appetite. o Constipation. o Bradycardia. o Eventual myxoedema coma.
When would you use levothyroxine?
We use this in 3 scenarios:
§ Autoimmune primary hypothyroidism.
§ Iatrogenic primary hypothyroidism – e.g. post-thyroidectomy.
· Oral form and the dosage is based off the high TSH levels (aim to supress the TSH into reference ranges.
§ Secondary hypothyroidism – e.g. pituitary tumour.
· Oral form BUT TSH is low due to adenohypophysial failure so you can’t use it as a guide so you aim to move the fT4 to the middle of reference range.
what happens in Thyroid Hormone Over-replacement ?
Adverse effects of thyroid hormone over-replacement are:
§ Skeletal – increased bone turnover, reduction in bone density (osteoporosis).
§ Cardiac – tachycardia, risk of dysrhythmia and atrial fibrillation.
§ Metabolism – increased energy expenditure, weight loss.
§ Increased beta-adrenergic sensitivity – tremor, nervousnes
thyroid hormone mechanism of action
thyroxine enters the target cell and is converted to T3 by deiodinase
T3 then moves to the nucleus and binds to the thyroid hormone receptor.
It then heterodimerises with a retinoid X receptor
this complex then binds to the thyroid response element that causes a change in gene expression
hypothyroidism symptoms
cold intolerance fatigue weight gain bradycardia depression constipation deepening of voice
production of thyroid hormone
Inside the colloid –
[1] Iodide ions in the presence of TPO (thyroperoxidase) and H2O2 (hydrogen peroxidase), are converted to a reactive iodine form.
[2] I* then iodinates one (MIT) or two (DIT) positions on TG (thyroglobulin) 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 à moves to the blood.
define primary hypothyroidism
Primary hypothyroidism (myxoedema) – autoimmune damage to the thyroid.
Adverse effects of thyroid hormone over-replacement are:
§ Skeletal – increased bone turnover, reduction in bone density (osteoporosis).
§ Cardiac – tachycardia, risk of dysrhythmia and atrial fibrillation.
§ Metabolism – increased energy expenditure, weight loss.
§ Increased beta-adrenergic sensitivity – tremor, nervousness
