thyroid drugs in practice Flashcards
what does the thyroid gland produce?
T3 and T4
T3= tri0iodothyronine
T4= thyroxine- converted to the more biologically active T3 in peripheral tissues
what is the production of T3 and T4 essential for?
essential for normal growth, development and metabolism
how are the thyroid hormones controlled?
negative feedback:
the hypothalamus signals to the anterior pituitary via THS
Anterior pituitary signals to thyroid for production via THS
what are the types of thyroid disorders?
hypothyroidism- overt or subclinical
hyperthyroidism- overt of subclinical
goitre
thyroid cancer
why does thyroid disfunction in pregnancy need to be well controlled?
as there is trimester-specific reference ranges and differing clinical priorities needed careful management
what is usually done if a person who is pregnant is already taking levothyroxine?
a dose increase is usually needed
give an example of a drug induced thyroid disorder?
amiodarone- class 3 arrhythmic used to treat superventricular and ventricular tachyarrhythmias
how does amiodarone work to cause thyroid disorders?
hypothyroidism- block conversion of T4 to T3- compensatory increase in thyroid stimulating hormone
hyperthyroidism- due to iodine content of the drug
durg may mask clinical features of hyperthyroidism
what monitoring should be done with amiodarone?
TFT monitoring before- TSH, T3,T4, thyroid antibodies
and during treatment- TSH, T3, T4
and for a year after stopping- due to a long t 1/2
what happens if hypothyroidism occurs when taking amiodarone?
usually cautiously add in levothyroxine and continue amiodarone
how can lithium cause a thyroid disorder?
hypothyroidism- inhibits iodine uptake and thyroid hormone release- treat with levothyroxine replacement
hyperthroidism- paradoxical effect, mechanism unknown
what monitoring should be done with lithium?
TFT monitoring before and during treatment
what should TFTs be requested?
- clinical suspicion of thyroid disorder dur to presenting signs/ symptoms
- to rule out as part of a screening process e.g. osteoporosis, AF, subfertility, lithium, diabetes, autoimmune diseases
what happens in a TFT?
usually test TSH - and free T4
further testing - T3 and thyroid antibodies
other- biopsy, scans etc
how do you interperte TFT readings?
high TSH and low T4- hypothyroidism
low TSH and high T4= hyperthyroidism
high TSH and same T4= subclinical hypothyroidism
low TSH and same T4= subclinical hyperthyroidism
what is primary hypothyroidism?
primary- 95% failure of the thyroid gland to produce thyroid hormones -iodine def autoimune thyroiditis destruction of thyroid gland drugs congenital hypothyroidism
what is secondary hypothyroidism?
aprox 5%
under production of TSH by pituitary gland
-pituitary or hypothalamic dysfunction
tumors, surgery, trauma, radiotherapy
what is overt hypothyroidism?
may of may not be symptomatic
it is a decrease in T4 and an increase in TSH
what is subclinical hypothyrodism?
usually asymptomatic
many people do not need treatment- interval screenings of TFTS
if symptoms- trial of levothyroxine
same T4 and inc TSH
what are the clinical features of hypothyrodism?
fatigue cold intolerance weight gain non-specific weakeness arthrahia myalgia constipation menstrual irregularities depression impaired concentration and memory dry skin and reduced body and scalp hair thyroid pain
what are the signs of hypothyroidism?
changes to appearance- coarse dry hair and skin and hair loss
oedema
vocal changes- hoarsness or deepening of the voice
goitre
bradycardia
diastolic hpt
delayed releaction of deep tendon reflexes
paraesthesia
what are the complications of hypothyroidism?
CV complications- dyslipidaemia, CHD, HF
reproductive- fertility, complications in pregnancy
neurological- deafness, concentration, memory, language perception
myxoedema coma- medical emergency
how do you manage overt hypothyrodism?
often managed in primary care
1st line- levothyroxine - aim to resolve signs/ symptoms, normalise TSH
liothyronine- rarely used- endocrinologist
what dose of levothroxine should be given?
dose is adjusted based on clinical signs and symptoms of a biochemical response
1.6 mcg/kg/day- rounded to nearest 25 mcg for adults< 65
-higher starting dose- more rapid improvememys than lower followed by titration
inc 25-50 mcg increments every 3-4 weeks
usual maintenance 100-200 mcg increments every 3-4 weeks
when would you give a lower starting dose of levothyroxine?
if ischaemic heart disease or >60-65 years
25-50mcg adjusted in 25 mcg increments
what should you monitor for levothyroxine?
TSH and patients symptoms; adjust/ titrate dose
TFTs at least 3 montly until stable TSH reached then annually
what are the s/e of levothyroxine- usually associated with excess dosing?
GI disturbances CV arrhythmias, tachycardia flushing, fever, heat intolerence weight loss hypersensitivity rxn- rash, oedema muscle cramps, weakness anxiety, tremor, restlessness, insomnia mania menstrual irregularities headache
what does levothyroxine interact with?
calcium/ antacids/ iron salts
therefore take 4 hours apart
when should levothyroxine be taken?
ideally should be taken at least 30 min before brekfast, caffine containing liquids or other drugs
what is hyperthyroidsim?
excess of circulating thyroid hormones :dec TSH and inc T4
what is primary hyperthyroidism?
most commonly is graves disease- autoimmune
-antibodies stimulate and increase secretion of thyroid hormones
confirmed by testing for TSH receptor antibodies- secondary care
other causes- toxic multinodular goitre, toxic thyroid nodule, drugs eg- amiodarone/ lithium
what causes secondary HYperthyroidism?
TSH secreting pituitary tumour
what are some of the complications of hyperthyroidism?
cardiovascular- including arterial fibrillation and associated increased stroke risk
osteoproosis
eye disease- vision loss
thyroid storm- release of large am of thyroid hormone- worsening of symptoms
what are some of the clinical symptoms of hyperthyroidism?
Breathlessness, dysphagia, neck pressure (may be caused by a toxic multinodular goitre).Hyperactivity Emotional lability Insomnia, irritability, anxiety Palpitations Exercise intolerance Fatigue, muscle weakness Heat intolerance Increased appetite with weight loss Diarrhoea Infertility, oligomenorrhoea, amenorrhoea. Polyuria Generalized itch Reduced libido, gynaecomastia in men. Deterioration in blood glucose control and hyperglycaemia in people with diabetes mellitus
what are some of the signs of hyperthyroidism?
Agitation, fine tremor, warm moist skin, palmar erythema. Sinus tachycardia, atrial fibrillation, heart failure, dependent oedema. Eye signs. Goitre Gynaecomastia in men Splenomegaly Muscle wasting
how do you manage hyperthyroidism?
- Refer to specialist and consider following options:
- Surgery
- Radioiodine treatment
- Antithyroid drugs – carbimazole, propylthiouracil–Short-term while waiting for specialist review–Short-term in prep for radioiodine treatment or surgery–Medium-term in inducing remission of Grave’s disease–Long-term where radioiodine treatment or surgery is contraindicated or declined
- Consider prescribing a beta-blocker and titrating the dose depending on clinical response, to provide relief of adrenergic symptoms
what is radioiodine treatment?
- Induces damage of DNA leading to death of thyroid cells.
* Radioprotection measures after treatmen
who is radioiodine treatment not recommended for?
Not recommended for people with active thyroid eye disease as it may worsen this
•Contraindicated in pregnancy and in women who are breastfeeding.–Women should be advised to avoid becoming pregnant for at least six months after radioiodine treatment.–Men should be advised not to father children for at least four months after radioiodine treatment.
what happens to people with graves disease?
they become euthyroid and then hypothyrodi within 6 weeks to 6 months after completing radioiodine treatment
what are some anti-thyroid drugs? how do they work?
carbimazole and propylthyiouracil
•Decrease thyroid hormone synthesis, by acting as a preferred substrate for iodination by thyroid peroxidase, the key enzyme in thyroid hormone synthesis.
•Check FBC and LFT first.
carbimazole perfered
what risk does propylthiouracil pose?
Propylthiouracil has a small risk of severe liver injury (about 1 in 10,000)
what happens to people with graves disease who who have been taking carbimazole?
they can become euthroid after 4-8 weeks of treatment
how is the length of treatment adjusted with people with severe hyperthroidism , a large goitre or recent exposure to iodide?
may need a longer duration of treatment
how are anti-thyroid drugs given?
high dose usually carbmizole is given initially, the following repeat TFT, if things are improving, adjustment of medication by either:
-titration block regime- 40% -dose adj every 4-6 week/ if T4 falls too low or low-normal levels indicating hypothyroidism
block and replace regime-60%- the anti-thyroid drug is used to block the synthesis of thyroid hormone. T4 is monitored and levtthyroxine is added. adjustment to levothyroxine to maintain T4 levels in the range
remission rate about 50% if treatment is continued for 6-18 months and then stopped
what are the adverse effects of carbimazole?
nausea/ taste disturbances/ headache/ fever/ malaise/ arthralgia
itch and rahs- can usually be treated with antihistamines without the need to stop drug treatment
bone marrow suppression
hepatobiliary disorders
how should carbimazole be given?
15-40mg daily
reduced to maintenance dose of 5-15mg
usually for 12-18 months
or if using as part of a block and replace regime 40-60mg daily
what are the signs and symptoms of bone marrow suppression with carbimazole?
infection especially sore throat and fever
wbc count perferomed
and drug stopped
what are the s/e of propylthiouracil?
leucopenia
hepatic disorders
•Rarely, cutaneous vasculitis, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis, hypoprothrombinaemia, nephritis, lupus erythematous-like syndromes.
what dose of propylthiouracil should be given?
- 200 to 400mg daily in divided doses in adults
- Maintained until the patient becomes euthyroid; the dose may then be gradually reduced to a maintenance dose of 50 to 150mg daily in divided doses.
- Dose adjustments in renal impairment
