Hyperthyroidism Flashcards
State 2 common causes of hyperthyroidism.
Graves’ Disease Nodular goitre (Plummer's disease)
What type of disease is Graves’? Describe its mechanism.
Autoimmune
An autoimmune antibody is produced that binds to the TSH receptor thus stimulating thyroid hormone production
What does a thyroid gland look like in Graves’ Disease?
Smoothly enlarged (goitre) and the whole gland is active
State 8 features of Graves’ Disease.
Weight loss despite increased appetite Warm skin, excessive sweating Palpitations, tachycardia Tremor Pretibial myxoedema Exophthalmus Muscle wasting Oligomenorrhoea/ amenorrhoea
What are2 defining features of Graves’ and what is it caused by?
Pretibial myxoedema
Exophthalmos
Antibodies cause both of these
Describe the appearance of a thyroid gland of a Graves’ patient in a thyroid scan using radioactive iodine.
The whole gland is smoothly enlarged + the whole gland is overactive
What causes Plummer’s Disease?
A benign adenoma in the thyroid gland
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= hot nodule
The rest of the thyroid gland won’t be seen because the high thyroxine production will decrease TSH release, so the normal part of the thyroid gland won’t produce thyroxine + will not take up iodine
Describe the effects of thyroxine on the sympathetic nervous system.
Thyroxine sensitises beta adrenoceptors to ambient levels of A + NA
Thus causes symptoms of having excess adrenaline e.g. Tachycardia, Palpitations, Tremor in hands
What causes lid lag?
High adrenaline
What is thyroid storm (thyrotoxic crisis) and what are the features of thyroid storm?
A rare medical emergency. Features: Hyperpyrexia >41C Accelerated tachycardia/ arrhythmia Cardiac failure Delirium/ frank psychosis Hepatocellular dysfunction, jaundice
State 3 treatments for hyperthyroidism.
Thyroidectomy
Radioiodine
Drugs
What 4 classes of drugs are used in the treatment of hyperthyroidism?
Thionamides
Potassium iodide
Radioiodine
Beta-blockers (symptomatic relief)
What are thionamides used to treat and when would you use it?
Graves’ Disease + Plummer’s Disease
Could use before thyroidectomy to stabilise the patient (don’t want to give GA to tachycardic patient)
Could use to reduce symptoms while waiting for radio iodine to act
Describe the synthesis of thyroxine by follicular cells.
Thyroglobulin= a protein produced by follicular cells
Iodine is taken up by follicular cells
Thyroid peroxidase, in the presence of hydrogen peroxide, iodinates the tyrosyl residues on the thyroglobulin to produce monoiodotyrosine or diiodotyrosine
Peroxidase transaminase then couples MIT + DIT to form T3 + T4, which is stored in the colloid
What is the mechanism of action of thionamides?
Thionamides inhibit thyroperoxidase
This prevents iodination of thyroglobulin + coupling of MIT + 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 + stored in the colloid
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 e.g. Propranolol
This will reduce the effects of beta sensitisation by thyroxine
Other than its main function in inhibiting thyroperoxidase, what else do thionamides do?
Suppress antibody production (in Graves’)
Reduces deiodination of T4 to T3 in peripheral tissue
State 2 unwanted effects of thionamides.
Agranulocytosis (rare + reversible with withdrawal of the drug)
Rashes
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 + are present in breast milk so can cause foetal hypothyroidism
So give as low a dose as possible to a patient who is trying to conceive
Both drugs cross into breast milk but PTU does this less than CBZ
It is metabolised in the liver + excreted in the urine
What is the mechanism of action of potassium iodide treatment?
A massive dose of iodine can turn off the thyroid gland
It inhibits iodination of thyroglobulin + inhibits production of hydrogen peroxide
What is the Wolff-Chaikoff effect?
The temporary reduction in thyroid hormones following ingestion of a large amount of iodine
Why is potassium iodide useful before surgery?
It reduces the size + vascularity of the thyroid gland
State unwanted actions of potassium iodide.
Allergic reaction: Rashes, Fever, Angioedema
In what form is potassium iodide given? When are maximum effects seen?
Orally (Lugol’s Solution or Aqueous iodine)
Maximum effects after 10 days’ continuous administration
What is radioiodine use to treat?
Graves’ Disease
Plummer’s Disease
Thyroid Cancer
Describe the mechanism of action of radioiodine.
Radioiodine is taken up by the thyroid gland + accumulates in the colloid
It emits beta particles that destroy the follicular cells
Describe the pharmacokinetics of radioiodine.
Given orally as a single dose
Discontinue anti-thyroid drugs 7-10 days before
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 + breast feeding
Name another molecule that is cheaper and can be used instead of radioiodine.
Technetium 99 Pertechnetate
What is pretibial myxoedema?
Non-pitting swelling occurring on shins of patients with Graves’ disease
Growth of soft tissue
Name 2 thionamides
Propylthiouracil (PTU)
Carbimazole (CBZ)
What happens after prescription of thionamides + propranolol?
Aim to stop anti-thyroid drug after 18 months
No need for propranolol after a few weeks
Review patient periodically for remission/relapse
Why is propranolol used in treatment of hyperthyroidism?
It is a non-selective B blocker, so reduces tremor, slows HR + reduces anxiety
When is potassium iodide used?
In preparation of hyperthyroid patient surgery
In severe thyrotoxic crisis (thyroid storm)
