Therapeutics of thyroid disease Flashcards
Where is the thyroid gland located?
- Located in the neck region on the anterior surface of the trachea (just below the larynx)
Hormonal control pathway:
Hypothalamus –> pituitary –> thyroid gland –> T3 (most active) or T4 (given most in treatment, given in HYPOthyroidism)
What is the drug for T3?
liothyrinine
What is the drug for T4?
levothyroxine
What type of thyroid disease is the hypothalamus associated with?
tertiary thyroid disease
What type of thyroid disease is the pituitary gland associated with?
secondary thyroid disease (as a result of disease in the pituitary and is accompanied by a cohort of other diseases aswell)
What type of thyroid disease is associated with the thyroid?
Primary thyroid disease (T3 and T4 not produced)
Primary Hypothyroidism prevalence?
- At the level of the thyroid gland
- increased production of thyroid hormones
- Prevalence 2%, 10-20x more common in women (3.5% in women and 0.6% in men
Causes of hypothyroidism?
- Autoimmune disease (Hashimoto’s thyroiditis)
- Result of previous treatment (e.g. surgery) for hyperthyroidism
- Iodine imbalance (uncommon in UK as it is put in bread)
- Congenital hypothyroidism – where a child is born without a thyroid gland or a very small one (1 in 4000 children affected) If untreated, major development problems.
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 is a Thyroid Function Tests (TFTs)?
- Thyroid Stimulating Hormone (TSH)
- Free (unbound) T4
- Thyroid peroxidase antibody (rarely measured outside secondary care because T4 levels and TSH are very good at measuring)
- Primary Hypothyroidism:
• TSH, free (unbound) T4
Initial treatment of hypothyroidism?
- Adults ≤50 years – initially 50-100 mcg thyroxine daily, adjusted 25–50 mcg every 3–4 weeks according to response
- Adults >50 years & in heart disease - initially 25 mcg once daily, adjusted 25 mcg every 4 weeks (Start at lower dose if CVD risk)
- Congenital hypothyroidism – initially 10-15 mcg/kg for neonates (max 50 mcg), adjusted 5 mcg/kg every 2 weeks
- Measure TSH after 8-12 weeks (T½ of T4 = 7days) and three monthly until stabilised
hypothyroidism treatment – maintenance
- Usual maintenance dose
- 100-200 mcg adults
- 50-200 mcg children, depending on age
- Monitor TSH yearly for adults and every 4-6 months until puberty for children; aim for
- Lower half of reference range
- Symptom free
- Monitor for angina
Combination treatments for hypothyroidism?
- Liothyronine (t3) and levothyroxine (t4)
- Evidence shows no evidence of benefit over monotherapy
- Rarely used, usually only by endocrinologist when patient not responding to monotherapy
- Natural thyroid extract
- Desiccated animal thyroid gland
- Not recommended as no evidence of benefit
- Long term adverse effects uncertain
- Source of much debate on patient forums as available in US
Patient Counselling for hypothyroidism?
- Life-long treatment
- Single daily dose
- Do not take at same time as calcium or iron preparations or caffeine containing beverages – can effect absorption
- Three strengths of tablet – common cause of confusion as they look the same(25, 50, 100)
- Need for monitoring
- Entitled to medical exemption certificate for prescription charges (if primary or congenital)
Prevalence of 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 does a hyperthyroid patient look like?
- Anxious
- Palpitations
- Tremor
- Weight loss
- Tachycardia
- Goitre
- Heat intolerance
- Warm moist skin
- Difficulty sleeping
- Diarrhoea
Thyroid Function Tests (TFTs) for hyperthyroidism?
Thyroid Stimulating Hormone (TSH)
Free (unbound) T4
• Primary Hyperthyroidism
• TSH, free T4
Treatment Options – Drug Therapy for hyperthyroidism?
- Non-invasive
- Low risk of long term hypothyroidism
- Low long-term cure rate (<50%) for non-mild disease
- Rare but serious side effects requiring monitoring
- Drug treatment can be used either for suppression or to block and replace
- Carbimazole is the most common drug therapy used and is a pro-drug, with methimazole as the active drug
Drug therapy (thionamides) preferred for _____?
- Children
- Pregnancy, breast feeding (propylthiouracil only)
- Uncomplicated, mild disease
- Acute phase, prior to surgery or 131I
Carbimazole (active metabolite: methimazole) or propylthiouracil mode of action ?
• Interfere with thyroid hormone synthesis by inhibiting thyroperoxidase activity in follicular lumen
Carbimazole for hyperthyroidism?
- First choice drug
- Start with 15-40 mg daily (depends on severity of symptoms – can be higher)
- Maintain high doses until TFTs normal (4-8 weeks)
- Maintenance for 12-18 months
- by 25-30% monthly, until 5-15mg
- Longer-term treatment may be required if relapse – occurs in up to 50% of patients with non-mild disease
Blocking-replacement regimen (make the person completely hypothyroid)
- Carbimazole 40-60 mg for approx 4 weeks
- 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
Pregnancy and carbimazole?
- “Carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, especially in the first trimester and at high doses (daily dose of 15 mg or more).
- Women of childbearing potential should use effective contraception during treatment with carbimazole. It should only be considered in pregnancy after a thorough benefit-risk assessment, and at the lowest effective dose without additional administration of thyroid hormones—close maternal, fetal, and neonatal monitoring is recommended.” BNF
Propylthoiuracil regimen?
- 200-400 mg daily initially, in divided doses
- 50 mg three times a day maintenance
- Preferred in pregnancy, particularly in first trimester
- Intolerant of carbimazole (rash, agranulocytosis)
Carbimazole is associated with an increased risk of foetal nail abnormalities
CSM warning from BNF for Propylthoiuracil and Carbimazole:
- Both can cause bone marrow suppression
- decreased white cell count and increased infection
- 0.3-0.5% – abrupt onset & not dose related
- CSM warning BNF
- “Doctors are reminded of the importance of recognising bone marrow suppression induced by carbimazole and the need to stop treatment promptly.
- Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat.
- A white blood cell count should be performed if there is any clinical evidence of infection.
- Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.”
Patient Counselling (carbimazole)?
- Carbimazole as a single daily dose and Propylthiouracil in divided doses
- Duration of treatment & tapering to maintenance dose
- 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
- Patients on carbimazole who come into community pharmacies with a sore throat or mouth ulcers should be referred immediately to their GP, rather than sold over-the-counter treatments
- If on blocking-replacement regimen, then need counselling for both treatments
Radioactive iodine as treatment?
Radioactive iodine (131I) – Non-invasive – Excellent cure rate – Likelihood of long term hypothyroidism – Can worsen eye disease – Avoid pregnancy/fatherhood
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
Surgery for hyperthyroidism? (preferred for)
– Excellent and rapid cure rate – High likelihood of long term hypothyroidism – Invasive – Risk of damage to parathyroid gland – Scarring and possible swallowing difficulties • Surgery preferred for – Oesophageal obstruction – Intolerance to drug treatment – Young adults
131I or surgery??
• 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
Hyperthyroidism – adjuvant therapy?
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
Drug-induced Thyroid Disease. Iodine:
- 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
Drug-induced Thyroid Disease. Amiodraone? How?
• 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
Drug-induced Thyroid Disease. Lithium? How?
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
