Hyperthyroidism Flashcards
What are two types of hyperthyroidism?
Graves' disease Nodular Goitre (Plummer's disease)
Describe Graves’ disease
Autoimmune disease where the antibodies bind to TSH receptors in the thyroid and stimulate it. It produces more thyroxine and also causes the thyroid gland to grow.
Graves’ disease can be thought of as 3 things:
Goitre (smooth enlarged thyroid gland) caused by hyperthyroidism. Eyelid lag (the eye lid is closing is delayed)
Other antibodies bind to muscles behind the eyes causing exopthalmos.
Other antibodies causes pretibial myxoedema (hypertrophy of the shins)
What is pretibial myxoedema?
The swelling (non-pitting) that occurs on the shins of patients with graves disease: growth of soft tissue
What is Plummer’s disease?
This is not an autoimmune disease. Benign adenoma that is overactive at making thyroxine. Because it is not an autoimmune disease no antibodies are being produced = No exophthalmos, No pretibial myxoedema
See notes - normal side of the thyroid gland shrinks decrease in TSH from the high levels of T4 produced from the benign adenoma
How can diagnose graves disease?
See notes
Palpitation, radioactive iodine (or technetium cheaper)
How can you differentiate between graves and plummers?
See notes
Palpitations, scans
What are the effects of thyroxine on the sympathetic nervous system?
Sensitises beta adrenoreceptors to ambient levels of adrenaline. see notes
Tachycardia, palpitations, tremor in hands, lid lag
What are the symptoms of hyperthyroidism?
Weight loss despite = increased appetite Breathlessness Palpitations, tachycardia Sweating Heat intolerance Diarrhoea Lid lag and other sympathetic features
What is thyroid storm?
A medical emergency where you have extreme hyperthyroidism. 50% mortality if left untreated.
See notes for features of thyroid storm
Aggressive treatment
What are the treatment options for hyperthyroidism?
Surgery (thyroidectomy)
Radioiodine
Drugs
What are the classes of drugs used to treat hyperthyroidism?
1) Thionamides (thiourylenes; anti-thyroid drugs) - short term treatment
Propylthiouracil (PTU), carbimazole (CBZ)
2) Potassium iodide
3) Radioiodine
4) B-blockers
1,2 and 3 all reduce thyroid hormone synthesis. 4 helps with symptoms
How are thionamides used?
Daily treatment of Graves’ and Plummer’s disease
Treatment prior to surgery
Reduction of symptoms while waiting for radioactive iodine to act
See notes for reasons why
How is thyroxine synthesised?
See notes - its about the main steps which drugs can act on
Describe the mechanism of action of thionamides
Thionamides inhibit thyroperoxidase which is involved in the iodination of thyroglobulin and in the coupling reaction = reduction in the synthesis and secretion of thyroxine
Suppresses antibody production in graves’ disease
Reduces deiodination of T4 to T3 in peripheral tissue (PTU)
Usually aim to stop thionamides after 18 months, review patient. 50% chance of relapse
What is a problem with thionamides?
See notes - time of action vs clinical effects seen
non-selective b-blocker required to manage symptoms
Agranulocytosis - rare; urgent full blood count
Rashes
Describe the pharmacokinetics of thionamides
Carbimazole (prodrug) converted to methimazole
Plasma half life of 6-15 hours
PTU crosses the placenta less than CBZ. (And is secreted in the milk)
What is carbimazole converted to?
A prodrug converted to methimazole
Role of betablockers during thyrotoxicosis
It takes several weeks before clinical effects can be seen following the use of thionamides so you use b-blockers to manage the symptoms of tachycardia and tremors. You use non-selective betablockers (propanolol) so it can remove all the effects of excess stimulation to of beta adrenoreceptors.
What is the role of iodide treatment?
KI - dose that is 30 times the average daily requirement. This huge dose turns the thyroid gland off. You do this when you want the effect to take place quickly.
1) Preparation of hyperthyroid patients for surgery
2) Severe thyrotoxic crisis (thyroid storm)
Describe the pharmacokinetics of KI
Wolff-Chaikoff Effect = the temporary reduction in thyroid hormones following ingestion of large amounts of iodine. Autoregulatory phenomenon
The large amounts of KI causes the inhibition of iodination thyroglobulin and the generation of H2O2.
Works faster than anti-thyroid drugs (thionamides)
Given orally (lugol's solution; aqueous iodine) Maximum effect after 10 days' of continuous administration - short term because afterwards there is a sudden increase in thyroid hormones
What happens after the KI is administered?
Hyperthyroid symptoms are reduced within in 1-2 days
Vascularity and size of the gland also reduces within 10-14 days
What are unwanted action of KI?
Allergic reaction eg. Rashes, fever, angio-oedema
What does radioiodine treat and how?
It treats hyperthyroidism and thyroid cancers
Radioactive iodine accumulates in the colloid once it is taken in and emits beta particles of radiation which destroys the follicular cells.
Describe the pharmacokinetics and cautions of radioiodine
Discontinue anti thyroid drugs 7-10 days prior to radioiodine - ensures that the thyroid gland can become really active to suck up the radioiodine.
Single oral dose
Radioactive half life of 8 days
Radioactivity is negligible after 2 months
