Hypothyroid disorders Flashcards
What is primary hypothyroidism?
a.k.a myxoedema
Occurs as a result of autoimmune damage to the thyroid, causing thyroxine levels to decline and TSH levels to increase.
What are the symptoms of primary hypothyroidism (myxoedema)?
Deepening voice
Depression
Tiredness
Cold intolerance
Weight gain with reduced appetite
Constipation
Bradycardia
Eventual myxoedema coma
Everything slows down.
What is tetraiodothyronine?
a.k.a thyroxine, T4
A prohormone converted into the more active metabolite, triiodothryonine (T3) by deiodinase enzyme.
What is T3 derived from?
80% of circulating T3 is from deiodination of T4.
20% of circulating T3 is from direct thyroidal secretion.
T3 provides almost all the thyroid hormone activity in target cells.
What is the mechanism of action of thyroid hormones?
Thyroxine (T4) enters the target cell and is converted to T3 by deiodinase.
T3 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.
What drugs are used for thyroid hormone replacement therapy?
Levothyroxine sodium is usually the drug of choice (a.k.a thyroxine sodium, thyroxine, tetraiodothyronine, T4).
Liothyronine sodium (triiodothyronine, T3) is less commonly used.
What are the clinical uses of levothyroxine sodium (synthetic thyroxine)?
Primary hypothyroidism, e.g. autoimmune, iatrogenic (post-thyroidectomy, post-radioactive iodine). It is orally administered. TSH is used as a guidance for thyroxine dose- aim to suppress TSH into the reference range.
Secondary hypothyroidism, e.g. pituitary tumour, post-pituitary surgery or radiotherapy. It is orally administered. TSH is 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 the clinical use of liothyronine (synthetic T3)?
Myxoedema coma- a very rare complication of hypothyroidism. IV initially, as onset of action faster than T4, then oral when possible.
When would combined thyroid hormone replacement be used?
Some patients do not feel better with T4 even if their TSH is normal. Some of these patients feel better when they are given a combination of T3 and T4.
T3 is very potent so it is difficult to get the dose right.
It will switch off TSH and may lead to symptoms of toxicity: palpitations, tremor, anxiety.
What are the adverse effects of thyroid hormone over-replacement?
Usually associated with low/suppressed TSH.
Skeletal effects: increased bone turnover, reduction in bone mineral density, risk of osteoporosis.
Cardiac effects: tachycardia, risk of dysrrhythmia (particularly atrial fibrillation).
Metabolic effects: increased energy expenditure, weight loss.
Increased beta adrenergic sensitivity causing tremor and nervousness.
These are all symptoms of thyrotoxicosis.
What is the plasma half-life of levothyroxine (T4)?
6 days
What is the plasma half-life of liothyronine (T3)?
2.5 days
What percentage of circulating T3 and T4 is bound to plasma proteins?
- 97% of circulating T4.
- 7% of circulating T3.
Mostly bound to thyroxine binding globulin, TBG.
In what situations do plasma binding proteins increase?
Pregnancy.
On prolonged treatment with oestrogens and phenothiazines.
In what situations does TBG fall?
Malnutrition
Liver disease
Certain drug treatments
Certain co-administered drugs (e.g. phenytoin, salicylates) compete for protein binding sites.
