Therapeutics of Thyroid Disease Flashcards
Where is the thyroid gland located?
In the neck region, on the anterior surface of the trachea, just below the larynx
What hormone does the Hypothalamus produce?
TRH - thyroid releasing hormone
What hormone does the pituitary produce?
TSH - thyroid stimulating hormone
What hormones do the thyroid gland produce?
T3 (liothyronine - MOST ACTIVE) and T4 (levothyroxine - given to people as treatment)
What does T4 go on to produce?
rT3 and T3
What is primary thyroid disease?
(most common), when there is an issue with the thyroid itself, so T3 and T4 are not produced
What is secondary thyroid disease?
Issue in the pituitary and TSH is not produced (usually due to a series of other endocrine diseases)
What is tertiary thyroid disease?
A hypothalamic disorder with no hormones being produced (at the top of the chain)
What is hypothyroidism?
Decreased production of thyroid hormones at the level of the thyroid gland (more common in women)
What are the causes of Hypothyroidism?
- Autoimmune disease (hashimotos’s thyroiditis)
- result of previous treatment (ie surgery) - removal of thyroid
- Iodine imbalance (uncommon in UK) - we have iodine in flour
- Congenital hypothyroidism - child born without thyroid
What are the symptoms of hypothyroidism?
- Lethargy, weakness
- Dry scaly skin
- Sensitive to cold weather
- Depression
- Hair loss
- Memory loss
- Weight gain
- Constipation
- Puffy face and gruff voice with untreated disease
What do Thyroid Function Tests (TFTs) look at?
- Thyroid Stimulating Hormone (TSH)
- Free (unbound) T4
- Thyroid peroxidase antibody (rarely measured outside secondary care) – as it is an autoimmune disease
What levels of TSH and T4 are there in patients with primary hypothyroidism?
Increased TSH and decreased unbound T4 in the blood (pituitary still producing TSH as they want to try to stimulate T4)
How are raised TSH levels treated?
Treated with lifelong T4
What antibody is tested for in primary hypothyroidism?
TPO
What is the initial treatment for adults under 50 yrs?
initially 50-100 mcg thyroxine daily, adjusted 25–50 mcg every 3–4 weeks according to response
What is the initial treatment for adults over 50 and in heart disease?
initially 25 mcg once daily, adjusted 25 mcg every 4 weeks
If you rush in and give too higher a dose of T4 then you can cause heart disease or make their heart disease worse, this is why we gradually increase
What is the initial treatment for congenital hypothyroidism?
initially 10-15 mcg/kg for neonates (max 50 mcg), adjusted 5 mcg/kg every 2 weeks. Start this from 6-7 days old, they are then taking it for the rest of their life. As they are part of the physical and mental development they are often on higher doses to ensure development
When should TSH be measured during congenital hypothyroidism?
after 8-12 weeks (T½ of T4 = 7days) and three monthly until stabilised – as a child they may measure the levels more frequently to start with
What is the usual maintenance dose for adults and children with hypothyroidism?
- 100-200 mcg adults
* 50-200 mcg children, depending on age
How often is TSH monitored in hypothyroidism?
- Monitor TSH yearly for adults and every 4-6 months until puberty for children; aim for
* Lower half of reference range – upper limit is 4 so you want 0.5-2 as an aim
* Symptom free
What combination treatments for hypothyroidism are available?
Liothyronine and levothyroxine (although evidence shows no benefit over monotherapy)
What patient counselling is needed for hypothyroidism treatment?
- Life-long treatment
- Single daily dose
- Do not take at same time as calcium or iron preparations or caffeine containing beverages – as it affects the absorptions
- Three strengths of tablet – common cause of confusion, they all look exactly the same usually generic
- Need for monitoring
- Entitled to medical exemption certificate for prescription charges – if you have autoimmune disease, congenital hypothyroidism.
What is hyperthyroidism?
- Autoimmune (Grave’s disease)
- Toxic Nodules
- Antibodies to TSH receptor stimulate the gland
- INCREASED production of thyroid hormones
- Prevalence of 2% in women & 0.2% in men
What symptoms are present with hyperthyroidism?
- Anxiety
- Palpitations
- Tremor
- Weight loss – relatively quickly without trying
- Tachycardia
- Goitre
- Heat intolerance
- Warm moist skin
- Difficulty sleeping
- Diarrhoea
(symptoms are similar to cancer)
What levels of TSH and T4 are observed in hyperthyroidism?
DECREASED TSH and INCREASED T4 as pituitary thinks there is lots of T4 and stops producing TSH
What is there a low risk of in the treatment for hyperthyroidism?
Long term HYPOthyroidism - affecting the production of T3 and T4 rather than affecting the gland
What groups are thionamides preferred for?
- Children
- Pregnancy, breast feeding (propylthiouracil only)
- Uncomplicated, mild disease
- Acute phase, prior to surgery or radioactive iodine
What is the first choice drug for hyperthyroidism?
Carbimazole: interferes with thyroid hormone synthesis by inhibiting thyroperoxidase activity in follicular lumen
What doses are used for carbimazole?
- Start with 15-40 mg daily (depends on severity of symptoms – can be higher)
- Start treatment quickly as severe cardiac symptoms which you want to treat
- Maintain until TFTs normal (4-8 weeks)
- Maintenance for 12-18 months
- decrease by 25-30% monthly, until 5-15mg. reduce dose to have balance whilst treating symptoms and having lowest dose possible
- Longer-term treatment may be required if relapse – occurs in up to 50% of patients with non-mild disease
What risk is carbimazole associated with?
An increased risk of congenital malformations when used during pregnancy. Women of a childbearing age should use effective contraception during treatment.
Should only be considered during pregnancy at lowest effective dose with additional monitoring
What is the blocking-replacement regimen?
- Carbimazole 40-60 mg for approx 4 weeks – until the body has got rid of all their T3 and T4 they have
- THEN Carbimazole 40-60 mg PLUS thyroxine 50-100 mcg
- Makes patient temporarily hypothyroid
- Not eligible for free prescriptions
- Treat for up to 18 months
- Thyroid gland returns to normal function when stop treatment
- Not in pregnancy as only carbimazole crosses the placental barrier so you completely stop the babies thyroid production and they will have nothing to replace this – causing developmental issues
What drug can be used in hyperthyroidism if the patient is intolerant to carbimazole?
Propylthoiuracil: 200-400mg daily initially in divided doses
- 50mg TDS maintenance - preferred in pregnancy
What is drug induced agranulocytosis?
- linked to carbimazole
- Can cause bone marrow suppression
- decreased white cell count, leading to infection
What patient counselling is needed for carbimazole and Propylthiouracil?
- single daily dose for carbimazole, divided doses for Propylthiouracil
- Report signs of agranulocytosis: sore throat, mouth ulcer, bruising
- Report signs of hepatic dysfunction with Propylthiouracil: pruritis, jaundice, dark urine
- Advise on contraception if on carbimazole
- Need for regular review, tests
- Patients with hyperthyroidism ARE NOT entitled to medical exemption certificate for prescription charges
What other treatment options are available for hyperthyroidism?
Radioactive Iodine and surgery
What are the characteristics of radioactive iodine?
– Non-invasive – Excellent cure rate – Likelihood of long term hypothyroidism – Can worsen eye disease – Avoid pregnancy/fatherhood
What is radioactive iodine preferred for?
– First-line treatment except for mild disease or if radioactivity means is unsuitable – Failure to respond to drug treatment – Relapse after drugs – Comorbid cardiac disease – Toxic nodular goitre
What are the pros and cons of surgery for hyperthyroidism?
– Excellent and rapid cure rate
– High likelihood of long term hypothyroidism
– Invasive
– Risk of damage to parathyroid gland
– Scarring and possible swallowing difficulties
What is surgery preferred for in hyperthyroidism?
– Oesophageal obstruction
– Intolerance to drug treatment
– Young adults
What needs to be considered before using radioactive iodine or surgery for hyperthyroidism?
• Do not use either of these immediately after diagnosis
• Make patient euthyroid first using drugs for several weeks
• Prevent thyrotoxic crisis (thyroid storm) due to dangerously high levels of T4 released into system
– Hyperpyrexia, dehydration.
– Heart rate greater than 140 beats per minute, hypotension
– Nausea, vomiting, diarrhoea, abdominal pain.
– Confusion, agitation, delirium, psychosis, seizures or coma
What is adjuvant (additional) therapy in hyperthyroidism?
Beta-blockade:
• rapid relief of symptoms within 4 days: palpitations, anxiety, tremor
• C/I in asthma
• Propranolol, nadolol
• May need to be given 3-4 times per day as metabolism increased in hyperthyroidism
• Usually only needed for initial stages of treatment, when still symptomatic
What drugs can induce Thyroid disease?
Iodine, Amiodarone, Lithium
How can Iodine cause drug-induced thyroid disease?
- Overdose e.g. Radiographic contrast media
- Acute - inhibits release of T3/T4 from thyroid
- Prolonged – suppress T3/T4 production
- Rarely, can cause thyrotoxicosis if there is an underlying defect in autoregulation
- Iodine deficiency (very rare in UK) can cause hypothyroidism due to inability to produce T3/T4
How can amiodarone create drug-induced thyroid disease?
- Contains organic iodine
- Hypothyroidism
- Can occur at anytime in treatment – 1-10% of patients
- Inhibition of synthesis & release of T4 & T3
- usually continue amiodarone and start replacement T4 therapy if necessary
- Mild Hyperthyroidism
- Blocks conversion of T4 to T3, therefore increases TSH & T4
- Transient when start treatment – normalises in 3-4 months
- Severe hyperthyroidism
- Increased production of T4 because of iodine content
- Direct thyroiditis – excessive release of T4 into circulation
- Withdraw therapy, if possible or may use carbimazole
How does lithium create drug-induced thyroid disease?
- Hypothyroidism
- inhibits iodine uptake and prevents T3 & T4 release
- can be transient & subclinical
- monitor TSH
- start replacement T4 therapy if clinical
- Hyperthyroidism
- Rare, paradoxical effect
