Hyperthyroidism Flashcards
Describe the synthesis of thyroxine by follicular cells.
Thyroglobulin is a protein produced by the follicular cells. I- is taken up by the follicular cells
Thyroid peroxidase, in the presence of H2O2, iodinates the tyrosyl residues on the thyroglobulin to produce monoiodotyrosine or diiodotyrosine. Peroxidase transaminase then couples MIT and DIT to form T3 and T4, which is stored in the colloid
State two common causes of hyperthyroidism.
Graves’ Disease
Plummer’s Disease (toxic nodular goitre)
What type of disease is Graves’? Describe its mechanism.
Autoimmune
An autoimmune antibody is produced that behaves like TSH and binds to the TSH receptor thus stimulating thyroid hormone production
What happens to the thyroid gland in Graves’ disease?
Smooth, symmetrical hypertrophy due to overstimulation. Entire gland overactive in radioactive iodine scan.
State some features of Graves’ Disease.
Thyroid Rapid pulse Warm Excitability/nervousness Loss of weight Muscle wasting Oligomenorrhoea/amenorrhoea
Other antibody effects (defining features)
Localised pretibial myxoedema
Exophthalmos
What causes Plummer’s Disease?
It is caused by a benign adenoma in the thyroid gland
How does Plummer’s disease differ from Graves’?
NO pretibial myxoedema
NO exophthalmos
NOT autoimmune
Only Thyroidtoxicosis symptoms
What will a technetium or iodine scan of the thyroid show in a patient with Plummer’s Disease?
All the iodine will be taken up by the overactive, tumorous part of the thyroid so you will see a hot nodule appear
The rest of the thyroid gland will not be seen because the high thyroxine production will decrease TSH release from the anterior pituitary and so the rest of the thyroid gland that is responding to TSH will not produce any thyroxine and will not take up iodine
Describe the effects of thyroxine on the sympathetic nervous system.
Thyroxine sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline
So you get symptoms of having high adrenaline
What causes lid lag?
High adrenaline
What is thyroid storm (thyrotoxic crisis) and what are the features of thyroid storm?
This is a medical emergency that is a rare but important complication of hyperthyroidism Features: Hyperpyrexia Accelerated tachycardia/arrhythmia Cardiac failure Delirium/frank psychosis Hepatocellular dysfunction, jaundice
State four treatments for hyperthyroidism.
Thionamides
Potassium Iodide Radioiodine
Beta Blockers
What are thionamides (with examples) used to treat and when would you use them?
Graves’ Disease
Plummer’s Disease
You can use thionamides (such as Propylthiouracil or Carbimazole) before thyroidectomy to stabilise the patient (you wouldn’t want to give general anaesthetic to someone who is tachycardic with a labile heart rate)
It can be used after radioiodine treatment while you’re waiting for the clinical effects of the treatment
What is the pro-drug Carbimazole converted to become active?
Methimazole
What is the mechanism of action of thionamides?
Thionamides inhibit thyroperoxidase
This prevents the iodination of thyroglobulin and coupling of MIT and DIT. It also inhibits peroxidase transaminase
Why do thionamides have a delayed effect on thyroid hormone levels?
Thionamides are quick in inhibiting synthesis of thyroid hormone but it does nothing to the thyroid hormone that has already been synthesised and is stored in the colloid ready for release
So there is a big delay between the biochemical effects and the clinical effects
What would you give the patient temporarily whilst waiting for the thionamides to have their clinical effect?
Non-selective beta-blockers
This will reduce the effects of beta sensitisation by thyroxine
Other than their main function in inhibiting thyroperoxidase, what else do thionamides do?
Suppress antibody production (in Graves’)
Reduces deiodination of T4 to T3
State some unwanted effects of thionamides.
Agranulocytosis/granulocytopenia (rare and reversible with withdrawal of the drug) Nausea Headaches Rashes Jaundice Joint pain
What are the implications of thionamides in pregnancy?
Thionamides can cross the placenta and is present in breast milk so it can cause foetal hypothyroidism
This means that you would want to give as low a dose as possible to a patient who is trying to conceive and is taking thionamides
Both drugs cross into breast milk but PTU does this less than CBZ
It is metabolised in the liver and excreted in the urine
What is the mechanism of action of potassium iodide treatment?
If you give a massive dose of iodine it can turn off the thyroid gland (the Wolff-Chaikoff effect)
It inhibits the iodination of thyroglobulin and inhibits the production of hydrogen peroxide
Why is potassium iodide useful before surgery?
It reduces the size and vascularity of the thyroid gland
State some unwanted actions of potassium iodide.
Rashes
Fever
Angioedema
In what form is potassium iodide given?
Lugol’s Solution or Aqueous iodine
