Hyperthyroidism Flashcards
how is T4 made
1) Tsh binds to TSH receptors on follicular cells
2) production of TG and thyroperoxidase ( TPO)
3) iodine enters collide via Na+/I- transporters
4) TPO and hydrogen peroxide catalyse oxidation of Iodide –> iodine and TG + Iodine
5) Iodination of TG creates MIT or DIT ( mono and di iodothyronine)
6) Coupling reactions of MIT and DIT helped by TG + TPO/H2O2 form:
7) T3 ( 2 MIT) , T4 ( 2 DIT)
8) theses are cleaved from TG and transported in blood
Remember T4 is active thyroid hormone
What does thyroxine do
increase basal metabolic rate
What do you see in T4 /3 levels and TSH levels in primary hyperthyroidism
High T3/4 with low TSH ( remember T3 / T4 surprised TRH and pituitary due to -ve feedback)
For normal hydroid disease ( primary hyperthyroidism) what should be done to treat it
give levothyroxine dose until TSH becomes normal
Symptoms of hyperthyroidism
Weight loss despite increased appetite Breathlessness Palpitations , tachycardia Sweating ( feeling hot) Heat intolerance Diarrhoea Lig lag and other sympathetic features
What are the symptom of Grave’s disease
Heat intolerance
Raised metabolism → Increase in body temperature
Sweating
Weight loss
Higher basal metabolic rate
Despite increased appetite
Palpitations
Including atrial fibrillation or supraventricular tachycardias
breathlessness
Tremor
Exophthalmos (Proptosis)
Growth factor receptor immunoglobulins bind to muscles behind the eye
Smooth goitre
Oligomenorrhoea
Warm velvety skin
Occasional diarrhoea
Breast enlargement - gynecomastia in males
Muscle wasting
Breathlessness
Localised myxoedema
Pretibial myxoedema is the growth of soft tissue on the shin and associated (non-pitting swelling)
Lid lag and other SNS features.
Iodothyronines (thyroxine) sensitises GS linked beta-2-adrenoceptors (in sinoatrial node) to ambient levels of adrenaline and noradrenaline (NOT more adrenaline, just more sensitive receptors).
Leads to apparent SNS activation → tachycardia, lid lag, hand tremor etc.
Exophthalmos is autoimmune but lid lag is adrenaline driven
what is grave’s disease
When autoimmune antibodies (TSI) bind and stimulate TSH receptor in thyroid ( agonists)
this causes overactive thyroid g
describe the thyroid gland in grave’s disease
Smooth symmetrical goitre , can hear whooshing blood flowing through it ( bruit) as v active . Diffuse enlargement of thyroid ( even enlargement)
What are some symptoms only found in grave’s disease
smooth goitre
Exophthalmos
Pretibial myxoedema ( non pitting aka not fluid accommodation caused by heart disease swelling of shins)
Why does exophthalmos occur in grave’s disease
Antibodies attacking muscles of eye
How do you preform a scintigram
thyroid gland takes up iodine – only gland in the whole body to do so
if you give small doses of radioactive iodine123 to the patient, you can image the thyroid
in Graves’ disease, as there is even growth of the thyroid, the thyroid scan (scintigram)
Why can’t do do thyroid scans on pregnant women and what must you do instead
Radiation can harm children
better to do blood test for thyrotropin receptor antibody ( trab)
what does grave’s disease look live on a thyroid scan
Uniform radioiodine uptake , aka thyroid gland of even proportions but enlarged
What is plummer’s disease
and what is it’s other name
aka toxic nodular goitre - a bit of the thyroid gland has become tumorous and is misbehaving (autonomous thyroxine production - no TSH stimulation)
What will happen to TSH in toxic nodular goitre
TSH will be low
what is a solitary toxic nodule
A toxic adenoma, whereby a single nodule undergoes hypertrophy
and produces excess thyroid hormones.
How to you treat plummers
surgery / removal via radioiodine
What will you see on toxic nodular goitre on a thyroid scan
Uneven distribution of size
Because there is too much thyroxine coming from the tumour part of the thyroid, the pituitary will stop making TSH and the normal part of the thyroid will slowly shrink and stop making thyroxine (suppressed by tumour)
This means that in the thyroid scan you will just see a hot nodule and the rest of the thyroid scan will not be seen
( aka will feel only on one side of neck(
What is viral thyroiditis or de quavrain’s
when a virus causes hyperthyroidism
Describe the mechanism of viral thyroiditis
acute inflammation of thyroid gland induced by viral infection
reduced thyroxine output, viral replication proceeds instead ( aka no thyroxine being made)
Stored thyroxine is released instantaneously from damaged thyroid follicles: Hyperthyroidism (1 month)
around four weeks, stored thyroxine is depleted: hypothyroidism
After another month, the cells will have recovered and will start to produce thyroxine again so they will return to normal
Patient then becomes euthyroid (normal functioning thyroid) again
What is special about viral thyroiditis
pateint will become hyperthyroid and then get hyperthyroidism ( due to depletion of T4 stores)
What will you see in terms of T4/TSH in viral thyroiditis
Low TSH , high free T4
Symptoms of viral thyroiditis
Painful dysphagia
Hyperthyroidism
Pyrexia (fever)
Raised erythrocyte sedimentation rate: the rate at which red blood cells sediment in one hour
Pain radiating to ear
Tender pretracheal lymph nodes
Thyroid gland tender and visibly enlarged (on one side)
What will you see of a viral thyroiditis thyroid scan
) iodine uptake –> not detected on thyroid scan using radioiodine isotope
What is the difference between viral and post partum thyroiditis
Postpartum thyroiditis is similar but without pain symptoms and only occurs after pregnancy due to immune system tolerance in pregnancy - bounce back after birth where if you have a history of autoimmune disease you may present autoimmune symptoms (can happen to anyone but more likely if you have had autoimmune disease)
What is the effect of thyroxine on the sympathetic nervous system
Increases sensitivity of beta adrenoceptors to ambient ( normal) levels of adrenaline and noradrenaline
Thus there looks like there is apparent sympathetic activation
Patients present with tachycardia , palpitations , tremor in hands and lid lag ( slow at closing eyes)
What is a thyroid storm
Uncontrolled hyperthyroidism
Remember this is v dangers 50% of those untreated will die
Symptoms of a thyroid storm
Hyperpyrexia – high fever (>41). Accelerated tachycardia/arrhythmia. Cardiac failure. Delirium/frank psychosis. Hepatocellular dysfunction, jaundice. Hypertension
Treatment of thyroid storms
Surgery (thyroidectomy)
Singers should avoid due to risk of voice change also risk of ( losing parathyroid glands , scarring and anaesthtic)
Radioiodine
One dose : cure
Emanate radioactivity - patient who was a teacher had to take time off ( 2 weeks)
Not given to kids
Drugs (
Why should singers avoid thyroidectomies as treatment for hyperthyroidism
Singers should avoid due to risk of voice change also risk of ( losing parathyroid glands , scarring and anaesthtic)
What drugs can be used to treat hyperthyroidism
Thionamides (thiourylenes; anti-thyroid drugs):
Propylthiouracil (PTU).
Carbimazole (CBZ).
Beta-blockers. This combats the symptoms of hyperthyroidism but doesn’t treat it
What are thioamides used for ?
Daily treatment of hyperthyroid conditions – e.g. Graves’, Toxic thyroid nodule.
Treatment prior to surgery.
Reduction of symptoms while waiting for radioactive iodine to act.
When should you stop anti thyroid drugs
18 months after first use ( review pateint periodically including thyroid function tests fore relapses)
What is the mechanism of action for thioamides
Thioamides inhibit thyroid peroxidase (and peroxidase transaminase) action within follicular cells, therefore reducing the activation of iodide into iodine and inhibiting T3/T4 synthesis (Limits iodination of tyrosine residues of thyroglobulin).
Thionamides cannot do anything about thyroxine already in the colloid – so takes some time to take effect
While waiting for thioamides to take effect what should be used?
Beta blockers are non-selective (propranolol and atenolol)
why is PTU a better drug o use to treat hyperthyroidism in breastfeeding mothers?
Both drgus crosses the placenta and is secreted in the milk
Both drugs cross into breast milk but propylthiouracil does this LESS than carbimazole (PTU < CBZ)
So a breast feeding women will be put on PTU over CBZ
What type of a drug are carbimazoles
Carbimazole is a pro-drug which first has to be converted to methimazole to be active
Plasma half life of 6-15 hours
Why do you want low doses of thioamides in pregnant women
High doses of thionamides in a pregnant women could cause foetal hypothyroidism
What must you always consider when thinking about thyroid disease
Thyroid disease is common in women around reproductive age so you have to consider pregnancy
Side effects of thionamides
Agranulocytosis/granulocytopenia (reduction or absence of granular leukocytes ie neutrophils)
This is rare and reversible on withdrawal of the drug
Patients may present with a sore throat and a cold and they should go to the GP and have a full blood count
Sore throats and colds are very common but you don’t want to miss the cold that is caused by the patient being neutropenic
Rashes (relatively common)
Headaches
Nausea
Jaundice
Joint Pain
When do you use beta blokers
Sever weeks for thioamides to have clinical effect
Use non selective ( ie B1 / B2 blocker ) eg propranolol to reduce symptoms in interim
what are the 2 types of iodide treatement
KI
radioiodine
When is KI treatment used
Preparation of hyperthyroid patients for surgery. ( to reduce size of thyroid gland)
In severe thyroid storm/ thyrotoxic crisis patients.
What is the mechanism of action for KI
Inhibits iodination of TG. Inhibits hydrogen peroxide generation. WOLFF-CHAIKOFF EFFECT: Inhibition of thyroid hormone synthesis and secretion (TPO inhibition) Symptoms reduce in 1-2 days. Size of gland reduce in 10-14 days.
What is the wolff - chaikoff effect
Wolff-Chaikoff effect is an autoregulatory phenomenon, whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells, irrespective of the serum level of thyroid-stimulating hormone (TSH)
What are some unwanted side effects of KI
Allergic reactions
When is KI most effective
After 10 days ( must complete surgery in this time frame)
what is the mechanism of action for radioiodine
Radioiodine will accumulate in the colloid and emit beta particles – this will destroy the follicular cells and switch off the thyroid gland
Thyroxine will then have to be taken as treatment to prevent hypothyroidism
What must be taken after radioiodine treatment to prevent hypothyroidism
Thyroxine
Why must pateints stop anti - thyroid drugs before radioiodine treatment
Patients taking anti-thyroid drugs will stop these a couple of days before taking radioiodine – This will allow the thyroid gland to be slightly overactive so that the radioiodine is taken up more quickly
How is radioiodine administered
Administered as a single oral dose: 370MBq (10mCI) of iodine 131 isotope.
What are the negative consequences of radioiodine treatment
must isolate at home for 10 days after treatment to ensure not spreading ionisation to children ( esp babies)
must take thyroxine to prevent hypothyroidism
What else is radioiodine used in ( not just treatment)
Thyroid scans
What other chemical can be used in thyroid scans
99-Tc pertechnetate is an option for low dose tracer
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