Hypothyroidism Flashcards
Describe what happens in the colloid
- Iodide ions in the presence of TPO and H2O2, are converted to a reactive iodine form
- I* then iodinates one (MIT) or two (DIT) positions on TG to create mono-iodotyrosines (MIT) or di-iodotyrosines (DIT) –
- TPO and H2O2 then catalyse a coupling reaction to create tri-iodothyronines (T3) or tetra-iodothyronines (T4)
- Lysosomes then uptake clumps of colloid which is broken down to liberate T3 and T4
- T3/4 move to the blood (liberated by lysozymes)
What is primary hypothyroidism?
myxoedema - usually caused by autoimmune damage to the thyroid. Can be iatrogenic - post-thyroidectomy, post-radioactive iodine
What are TSH and thyroxine levels like in primary hypothyroidism?
TSH - high
T4 - low
What are the symptoms of hypothydroisim?
- bradycardia
- cold intolerance
- deepening voice
- weight gain, reduced appetite
- constipation
- depression and tiredness
- eventually coma
Which enzyme converts T4 into T3 and why?
T3 is bioactive form and done by deiodinase
What is circulating T3 made from?
- 80% from T4
- 20% from thyroid directly
How does T3 perform its function?
T3 travels to the nucleus and binds to a heterodimer of TR and RXR. This then bonds onto the DNA part called the TRE. This then causes effects
What is thyroid hormone replacement therapy?
Patients given T4 commonly (which they then convert themselves to T3)
- The thyroxine given is called levothyroxine sodium.
Which 3 scenarios would thyroxine (T4) be given?
- Autoimmune primary hypothyroidism
- Iatrogenic primary hypothyroidism – e.g. post-thyroidectomy. Oral form and the dosage is based off the high TSH levels
- 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
When may T3 be given and what is it called?
Liothyronine sodium
Used when you want a rapid effect – e.g. in a myxoedema coma. This is given intravenously.
What is combined thyroid hormone therapy and what are the risks of it?
A combination of T4 and T3.
However, T3 is so potent that you often get effects of excess hormones and a “toxicity” effect – palpitations, tremors, anxiety etc. (caused by v low TSH)
What are the adverse effects of over replacing thyroid hormones?
Low/supressed TSH
- 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
Which of the two drugs are active orally?
both
What are the half lives of the two thyroid drugs?
Levothyroxine (T4) – 6 days
Liothyronine (T3) – 2.5 days
How much of T4 and T3 are bound to plasma proteins?
Approx. 99.97% (T4) and 99.7% (T3) are bound to plasma proteins (PPB) (mainly TBG – Thyroxine Binding Globulin).
