Hyperthyroidism Flashcards
State two common causes of hyperthyroidism.
Graves’ Disease
Plummer’s Disease (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 in the thyroid thus stimulating thyroid hormone production
What does a thyroid gland look like in Graves’ Disease?
The thyroid gland is smoothly enlarged and the whole gland is active
State some features of hyperthyroidism.
Weight loss despite increased appetite Breathlessness, palpitations, tachycardia Sweating Heat intolerance Diarrhoea Lid lag and other sympathetic features
Graves also has:
- Exophthalmos
- Pretibial myxoedema
What are two defining features of Graves’ and what is it caused by?
Exophthalmos - antibodies bind behind the eye
Localised pretibial myxoedema - different antibodies bind causing hypertrophy of shins and ankles (non-pitting)
Describe the appearance of a thyroid gland of a Graves’ patient in a thyroid scan using radioactive iodine.
The whole gland is smoothly enlarged and the whole gland is overactive
Should see a smooth lump (cold nodule=cancer)
What causes Plummer’s Disease?
It is caused by a benign adenoma in the thyroid gland that is overactive and making thyroxine
How does Plummer’s disease differ from Graves’?
NO pretibial myxoedema
NO exophthalmos
NOT autoimmune
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 e.g. lid lag, tachycardia, tremor, palpitations.
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 - 50% mortality if untreated. It is a rare but important complication of hyperthyroidism
Features: Hyperpyrexia >41oC Accelerated tachycardia/arrhythmia Cardiac failure Delirium/frank psychosis Hepatocellular dysfunction, jaundice
State four treatments for hyperthyroidism.
Thionamides
Potassium Iodide Radioiodine
Beta Blockers
bblockers help with symptoms; other 3 reduce thyroid hormone sythesis
State two thionamides.
Propylthiouracil PTU
Carbimazole CBZ
What are thionamides used to treat and when would you use it?
Graves’ Disease
Toxic thyroid goitre
- You can use it 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
Describe the synthesis of thyroxine by follicular cells.
- Thyroglobulin is a protein produced by the follicular cells
- Uptake of iodide (AT) - Iodine is taken up by the follicular cells by active transport
- Iodination: THYROID PEROXIDASE, in the presence of hydrogen peroxide, iodinates the tyrosyl residues on the thyroglobulin to produce monoiodotyrosine or diiodotyrosine
- Coupling reaction: PEROXIDASE TRANSAMINASE then couples MIT and DIT to form T3 and T4, which is stored in the colloid
- This is then endocytosed and secreted
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 thethionamides to have their clinical effect? Why?
Non-selective beta-blockers E.G PROPRANOLOL/ATENOLOL
This will reduce the effects of beta sensitisation by thyroxine
It takes several weeks for the ATDs to have clinical effects e.g. reduced tremor, slower HR, less anxiety. So bb’s can achieve these effects in the interim.
Other than its main function in inhibiting thyroperoxidase, what else do thionamides do?
- Suppress antibody production (in Graves’)
2. Reduces deiodination of T4 to T3 in peripheral tissues
State some unwanted effects of thionamides.
- agranulocytosis (usually reduction in neutrophils) - rare and reversible on withdrawal of drug.
- rashes (relatively common)
Carbimazole is a pro-drug. What is it converted to become active?
Methimazole
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
- It inhibits the IODINATION step of thyroglobulin
- Inhibits the production of hydrogen peroxide + thyoperoxidase
What is the Wolff-Chaikoff effect?
The temporary reduction in thyroid hormones following ingestion of a large amount of iodine - presumed AUTOREGULATORY effect
Why is potassium iodide useful before surgery? How early must it be given?
It reduces the size and vascularity of the thyroid gland
This happens in 10-14days
State some unwanted actions of potassium iodide.
Allergic reaction e.g. Rashes , Fever, Angioedema
In what form is potassium iodide given?
Lugol’s Solution or Aqueous iodine
What is radioiodine use to treat?
Iodine 131 is used to treat Graves’ Disease, toxic nodular disease (Plummer’s) and Thyroid Cancer
Describe the mechanism of action of radioiodine.
Radioiodine is taken up by the thyroid gland and it accumulates in the colloid
From the colloid it emits beta particles that destroy the follicular cells
Describe the pharmacokinetics of radioiodine.
It is given orally as a single dose
Discontinue anti-thyroid drugs 7-10 days before radioiodine treatment
Half-life = 8 days
Radioactivity is negligible after 2 months
What are some cautions of radioiodine?
Avoid close contact with small children for several weeks after receiving radioiodine
Contra-indicated in pregnancy and breast feeding
Name another molecule that is cheaper and can be used instead of radioiodine.
Technetium 99 Pertechnetate
State some symptoms of viral thyroiditis (de Quervain’s thyroiditis).
Painful dysphagia
Pyrexia
Hyperthyroidism
Raised ESR
Describe how viral thyroiditis causes hyperthyroid effects.
The virus takes over the function of the thyroid and makes the thyroid produce more virus particles rather than producing thyroid hormone
It damages the thyroid follicles so that all the thyroxine gets released
Though the virus is stopping the production of thyroid hormone, the patient actually presents with hyperthyroid symptoms because of the release of stored thyroid hormone
What is the appearance of a thyroid scan in a patient with viral thyroiditis?
It is not visible in the scan because the thyroid gland isn’t taking up any iodine because no thyroid hormone is being synthesised
Describe the progression of viral thyroiditis from the time of presentation with hyperthyroid symptoms.
As it is viral, you just wait for the virus to eventually leave
Eventually, all the stored thyroxine in the colloid will run out (after around 4 weeks) –> hypothyroid symptoms
After another 4 weeks the cells would have recovered and will start to produce thyroxine again so it will return to normal (euthyroid)
How long does it take to see the biochemical and clinical effects of thionamides?
Biochem effect - hours
Clinical effect - weeks
When is idodide (KI) treatment given to patients?
- In prep of hyperthyroid patients for surgery
2. Severe thyrotoxic crisis (thyroid storm)
How quickly do hyperthyroid symptoms reduce after KI teratment?
Hyperthyroid symptoms reduce within 1-2days
Why should anti-thyroid drugs be discontinued prior to radioiodine treatment?
to allow time for the thyroid to become really active again so that it takes up a lot of thyroid hormone
