L 45. Thyroid Disorder Flashcards
4x functions of the thyroid gland
- Hormone production
- Growth
- Development
- Regulation of energy metabolism
Epidemiology of thyroid function x3
- More common in women
- Hypo prevalence increases with pregnancy and age
- Most common dysfunctions = hypothyroidism and hyperthyroidism.
Patient assessment for thyroid dysfunction.
Is routine screening/asymptomatic testing recommended?
1. Patient history
2. Physical examination
3. TSH measures.
Routine screening/asymptomatic testing is not recommended.
High suspicion symptoms of hypothyroidism x2?
Goitre, delayed reflexes
Intermediate suspicion symptoms of hypothyroidism x7
Fatigue Weight gain Cold intolerance Dry/rough/pale skin Constipation Facial swelling Hoarseness.
Low suspicion/non-specific symptoms of hypothyroidism x7
Dry hair/hair loss Muscle cramps/aches Depression Irritability Memory loss Abnormal menstrual cycles Decreased libido
High suspicion symptoms of hyperthyroidism x4
Goitre
Thyroid bruit (sound)
Eyelid lag/droop (Ptosis)
Eye bulging (proptosis)
What does ptosis and proptosis mean?
Ptosis: eyelid droop
Proptosis: bulging eyes
Intermediate suspicion symptoms of hyperthyroidism x7
Fatigue Weight loss Heat intolerance/sweating Fine tremor Increased bowel movements Fast heart rate/palpitations Staring gaze
Low suspicion/non specific symptoms of hyperthyroidism x7
Nervousness Insomnia Breathlessness Light/absent menstrual periods Muscle weakness Warm/moist skin Hair loss
Symptoms of hypothyroidism (x3)
Fatigue/lethargy/sleepiness
Cold intolerance
Dry skin
Hypothyroidism treatment goals x3
Replace missing hormones
Relieve signs and symptoms
Achieve euthyroid state
What is a euthyroid state
Normal thyroid function/TSH within the reference range
… is the synthetic form of T4.
… is converted into the more active form, … in the peripheral tissue via peripheral……
Levothyroxine is the synthetic form of T4.
T4 is converted into the more active form, T3, in the peripheral tissue via peripheral deiodination.
Why is levothyroxine the drug of choice for hypothyroidism?
It is reliable, it relieves symptoms, it is safe, and it stabilises thyroid function tests.
Potential issues with elderly or IHD patients with levothyroxine.
Therefore how must we approach the dosing?
Increased metabolic activity = increased cardiac stimulation = arrythmias, angina, MI
TTherefore need to do initial low dose and then titrate.
Dosing of levothyroxine
Adult: 500-100mcg od before breakfast. Titrate 25-50mcg every 3-4 weeks according to response.
In cautioned patients, consider 25mcg of and adjust by +25mcg every 4 weeks.
What is maintenance dose for levothyroxine in adults in and patients with cautions?
100-200 mcg daily in adults
50-200mcg daily in cautioned patients
Dose adjustments occur for levothyroxine when…
Monitoring timeframes.
Dose is titrated according to blood test results
Monitor TSH 6-8 weeks after initiating treatment.
Adjust if necessary, recheck in 6-8 weeks and check symptoms.
If patient stable, monitor TSH every 6-12 months.
Why is the monitoring of levothyroxine only every 6-8 weeks?
Steady state takes 6-8 weeks to reach therefore show clinical benefit. Must wait until then to determine the effects of the medicine.
ADRs of levothyroxine (at excessive doses)
Hyperthyroidism symptoms:
Diarrhoea, headache, flushing, sweating, fever, heat intolerance
Increased appetite but weight loss
Tachycardia, arrhythmias, palpitations, hypertension
Tremor, restlessness, excitability
Insomnia, muscle cramp, muscular weakness
Menstrual irregularities, impaired fertility
Food/diet interactions of levothyroxine
Many foods/ions decrease the gut absorption of levothyroxine (e.g calcium, iron, antacids, cholestryamine). Therefore should take it on an empty stomach.
Drug-food interactions: soy, high fibre diet.
Drug interactions with Levothyroxine x4
The following CYP inducers increase the metabolism of levothyroxine, therefore an increased dose is required: Phenytoin Carbamazepine Oestrogen (HRT) Rifampicin
Levothyroxine brands x3
Synthroid
Eltroxin
Levothyroxine (mercury Pharma)
IMP POINT WHEN CONSIDERING LEVOTHYROXINE BRANDS
Brands are NOT interchangable.
They have the same active ingredient
Different excipients –> diff absorption –> diff bioavailability
What is a section 29 (unfunded) drug used for severe hypothyroidism?
Liothyronine (T3)
Is used to treat myxedema coma (severe hypothyroidism, life threatening).
PK of liothyronine (onset, t0.5 - not values but describing words)
Rapid onset, short t0.5 therefore reaches therapeutic concs.
Dosing for liothyronine in myxedema coma
IV injection if in coma.
10-20mg/day increased to 20mcg tds.
Hyperthyroidism is considered to be a … disease
Hyperthyroidism is considered to be a subclinical disease
What are the differences between subclinical and overt hyperthyroidism?
Subclinical: mild form, TSH is below normal but free T4/T3 is within the normal range. Few or no symptoms.
Overt hyperthyroidism: TSH lower than normal, free T3 and or T4 are above normal, hyperthyroidism symptoms will always be present (e.g sweating, weight loss etc)
Treatment goals for hyperthyroidism x4
Relieve signs and symptoms
Decrease thyroid production
Achieve euthyroid state
Prevent complications
Complications of hyperthyroidism x3
Loss of bone density, CVD, graves (opthalmopathy and dermopathy)
Management of hyperthyroidism is dependent on: (x5)
Cause and severity of disease Age Goitre size Concurrent medications/co-morbidities Patient preference
MoA of thionamides
Competitively inhibit thyroid peroxidase –> decreased oxidation and binding of iodine (!!) –> decreased T4/T3 synthesis.
NOTE: PTU also inhibits the conversion of T4 to T3
What does MMI and PTU stand for?
MMI = metabolite methimazole PTU= propylthiouracil
Initial carbimazole/methimazole dosing.
How long is therapy normally continued for?
Adult: 15-40mg/day (divided) for 4-8 weeks then until euthyroid.
Reduce dose gradually and adjusted according to response.
Therapy normally continued for 12-18 months
PTU initial dosing
200mg-400mg daily (divided) until euthyroid, then gradually reduce dose to 50-150mg daily (divided)
Can PTU or methimazole be used in pregnancy?
Which has a shorter t0.5?
Which has 10 fold lower activity?
PTU can be used in pregnancy.
PTU has a shorter half life.
PTU has 10 fold lower activity than methimazole.
Advantages of both carbimazole (x2) vs PTU (x4)?
No clear advantage of one over the other.
Carbimazole is most common. Can be given OD, may have better overall safety profile (less hepatoxicity)
PTU additionally inhibits T4 –> T3 conversion, can be used in pregnancy, short t0.5, but can cause severe liver injury.
What does “block and replace” mean in terms of thyroid treatment?
High doses of carbimazole to block thyroid function
+ levothyroxine and titrate until euthyroid.
Given for 18 months, not suitable during pregnancy.
ADRs of thionamides (minor + serious)
Minor: rash, fever, GI upset (treat symptoms)
Serious: bone marrow suppression –> agranulocytosis (low WBC count) = DISCONTINUE DRUG!
Patient counselling of ADRs for thionamides?
Report symptoms of: fever, sore throat, or infection
What is the serious side effect of thionamides? What should occur in this case?
AGRANULOCYTOSIS.
Discontinue drug immediately.
Why are B blockers used for thyroid treatment?
They provide relief of adrenergic symptoms, and can inhibit the conversion of T4 to T3 (but don’t reduce synthesis).
When do you start a thyroid patient on B blockers and when do you stop?
What are the most common B blockers given to thyroid patients?
Start when diagnosed for hyperthyroidism for symptomatic relief.
Continue until euthyroid occurs.
Most common: propanolol and nadolol.
Radioactive iodine: What does it do? What % is euthyroid after a single dose? Whomst can it be used for? Is it better or worse when compliance is an issue? Why? What is the risk of it?
Removal of body tissue (thyroid) without surgery = thyroid ablation
90% euthyroid after a single dose
Can be used for all ages, those with cardiac disease or when having a relapse after partial thyroidectomy.
Good when compliance is an issue - one dose!
Risk: permanent hypothyroidism (lifelong monitoring required)
Non-pharm options for hyperthyroidism
What are the usual indications for this method?
Partial thyroidectomy
- if failure to respond to medical treatment, intolerance to anti-thyroid meds, pressure of goitre onto trachea/oesophagus, or cosmetic issues.
Summer of hyperthyroidism treatment
- 1st line for Grave’s disease
- Additional drugs to first line
- 2nd line
- Non-pharm option
1st line: Carbimazole
Additional drugs: B blockers for symptomatic relief (and propanolol inhibits T4 to T3)
2nd line: radioactive iodine (also for relapse after drug treatment)
NP option: thyroidectomy
Which drugs can induce thyroid dysfunction?
Amiodarone and lithium
What is the MoA of amiodarione inducing thyroid dysfunction?
Amiodarione has a high iodide content and a toxic effects on the thyroid. It also decreases peripheral conversion of T4 to T3.
What is the MoA of lithium inducing thyroid dysfunction?
What parameters need to be monitored?
Decreases synthesis and secretion of thyroid hormones.
Need to monitor: TSH, free T4 and free T3
