Hyperthyroidism & Thyroid disorders Flashcards
What is the process of thyroid hormone generation in the thyroid gland
TSH binds to TSH-R on follicular cell. Na+ and I- ions also co me and get into cell through sodium-iodide cotransporter
Iodide ions then move into the colloid where they’re oxidised to iodine (iodination)
The TSH binding causes production of thyroglobulin (prohormone) which is secreted into the colloid
TSH binding also causes activation of TPO (thyroid peroxidase) enzyme which, along with hydrogen peroxide, catalyses all iodination reactions
The iodine from before is added to thyroglobulin through iodination which produces 2 products (MIT and DIT)
A coupling reaction then results in production of T3 and T4 attached to TG
TG is then removed at lysosome and T3 and T4 are released into bloodstream
Hypothalamic control of thyroid activity
What does this mean when thyroid gland is destroyed due to autoimmunity
How is this useful in treatment
Hypothalamus releases TRH which stimulates TSH release from anterior pituitary which then acts on thyroid gland and stimulates release of thyroid hormone (T3 and T4)
Thyroid hormone exerts negative feedback on hypothalamus and anterior pituitary thus inhibiting release of TRH and TSH
Negative feedback is lost when thyroid gland is destroyed, resulting in increase in TSH.
Therefore when treating we give once daily levothyroxine till TSH levels fall to normal.
what is graves disease
autoimmune cause of hyperthyroidism
what are the symptoms of hyperthyroidism specific to graves disease?
smooth, diffuse goitre (diffuse enlargement and engorgement)
exophthalmos
pretibial myxoedema
what are the generalised symptoms of hyperthyroidism?
Mental changes
heat intolerance, sweating, facial flushing
Smooth diffuse goitre (may have thrill and bruit)
tachycardia, palpitations, rapid pulse
Breathlessness
Breast enlargement (gynaecomastia in males)
weight loss despite increased appetite
diarrhoea
Menstrual disturbances
lid lag
tremors
Muscle wasting, weakness and fatigability
Warm velvety skin
what is the mechanism of graves disease?
anti-TSH receptor antibodies bind to and stimulate TSH receptors on thyroid gland
stimulates release of thyroid hormone
how does exophthalmos occur in graves?
the antibodies bind to muscles behind the eye
What is pretibial myxoedema and how does it occur in graves?
The swelling (non-pitting) oedema that occurs in the shins of patients with graves
soft tissue growth occurs due to antibody binding
how does graves disease appear on a radioiodine uptake test?
defined black thryoid - pyramidal lobe may be visible
Enlargement
what is plummers disease? How does this differ symptomatically from graves?
Toxic nodular goitre
a benign adenoma of the thyroid, overactive at making thyroxine
NO pretibial myxoedema
NO exophthalmos
how does toxic nodular goitre appear on a radioactive iodine uptake test?
What happens to the rest of the gland and why
less uniform uptake - hot nodules
not fully black
atrophy of rest of gland (because high thyroid hormone levels have negative feedback on hypothalamus and anterior pituitary, so rest of gland doesn’t receive stimulus to produce thyroid hormone
how does excess thyroxine stimulating the sympathetic NS present?
tachycardia, palpitations, tremors, lid lag (eyelid has partial sympathetic nerve supply)
how does excess thyroxine affect the sympathetic NS?
sensitises b-adrenoreceptors to ambient levels of adrenaline and noradrenaline
what is thyroid storm?
Medical emergency (50% mortality if left untreated)
Blood results confirm hyperthyroidism
hyperpyrexia >41c
accelerated tachycardia/arrhythmia >170bpm
cardiac failure
delirium/frank psychosis
hepatocellular dysfunction/jaundice
Need aggressive treatment
what are the main treatment options for hyperthyroidism?
surgery - thyroidectomy
radioiodine
Drugs- thionamides (propylthiouracil or carbimazole), potassium iodide, radioiodide, non-specific beta blockers to manage symptoms
what should be done in preparation for thyroidectomy?
potassium iodide for 10 days maximum
beta blockers to relieve symptoms
what are the most concerning side effects of thionamides?
agranulocytosis (usually reduction in neutrophils)- rare but reversible upon withdrawal
what is the most common side effect of thionamides?
rashes
how do thionamides reduce thyroxine synthesis?
How long does the biochemical effect take vs clinical effect
inhibit thyroid peroxidase and hence T3/4 synthesis
Biochemical effect- hours
Clinical effect- weeks
is thyroid treatment lifelong?
no - usually stopped after 18 months
Review patient periodically including thyroid function tests for remission/ relapse
(reviewed annually)
what is the mechanism of potassium iodide?
What does of KI is given normally?
inhibits thryoperoxidase + H2O2 generation
also inhibits iodination of thyroglobulin
Inhibits thyroid hormone synthesis through short term Wolff-Chaikoff effect- presumed auto regulatory effect
Normal does is x30 the daily iodine requirement
how long does KI take to have effect on the thyroid?
Hyperthyroid symptoms reduce within 1-2 days
Size and vascularity of the gland reduce in 10-14 days
what are the risks of thyroidectomy?
risk of voice change (recurrent laryngeal nerve)
risk of losing parathyroid glands
scar
anaesthetic
In what form do we use radioiodine to treat hyperthyroidism?
When is this contraindicated
What is 99-Tc pertechnetate used for
capsule containing 370MBq (10mCi) of I131
Contraindicated in pregnancy
Need to avoid children and pregnant mums for a few days
For scans only (not treatment), 99-Tc pertechnetate is an option.
destroys the thyroid gland
how does viral thyroiditis present?
Hyperthyroidism
Thyroid inflammation
painful dysphagia
pyrexia
painful upon palpitation
what is the mechanism of disease for viral thyroiditis?
virus attacks thyroid gland causing pain and tenderness
thyroid stops producing thyroxine and makes virus instead (thus no iodine uptake)
Stored thyroxine is released leading to hyperthyroidism initially
free T4 increases, TSH drops
However stores are depleted (takes ~4wks) then patient becomes hypothyroidic in 2nd month then during 3rd month it slowly resolves like normal viral illness
what does viral thyroiditis present similarly to?
Why does this type of thyroiditis occur
post-partum thyroiditis but no pain, and only occurs after pregnancy
Occurs due to immune system modulation during pregnancy
what is the role of beta blockers in thyrotoxicosis
It takes several weeks for ATDs to have clinical effects eg reduced tremor, slower heart rate, less anxiety
NON-selective (ie b1 & b2) b blocker
eg propranolol
achieves these effects in the interim
what beta blocker is given to someone with hyperthyroidism
propanolol
In what situations would KI generally be prescribed?
preparation of hyperthyroid patients for surgery
severe thyrotoxic crisis (thyroid storm)
