Transcript presentation source

Drugs and the thyroid
Dr Emma Baker
Senior Lecturer in Clinical
Pharmacology
Case 1. 60 year old woman
• Tired, loss of energy, feels the cold
• Constipated
• On examination
– croaky voice, slow relaxing reflexes
– Pulse 48bpm
• Question
– What is your differential diagnosis?
Investigations
• TSH
10mU/L
• Free T4 5pmol/L
• Cholesterol 8.5mmol/l
(0.5 - 4)
(12-25pmol/L)
(desirable <5.2)
• Question
– How do you explain these results?
Thyroid hormones
Hypothalamus
TRH
Pituitary
TSH
Negative feedback
Tyrosine
IODINE
Stored as
thyroglobulin
in thyroid
gland
Monoiodotyrosine
IODINE
Thyroid
gland
Diiodotyrosine
Thyroxine (T4)
Hypothyroid
T4
Thyroid binding globulin
3,3,5 triiodothyronine
rT3
3,3,5 triiodothyronine
T3
Questions
• How would you treat this condition?
• How quickly would you expect the
treatment to work?
• What precautions would you take when
starting treatment?
Thyroid replacement
• Thyroxine (T4) or rarely Liothyronine (T3)
• Pharmacokinetics
– well absorbed when given by mouth
– T4 takes 10 days to reach max. effect and wears
off after 2-3 weeks
– T3 has max. effect 1 hour, wears off in 1 week
• Pharmacodynamics
– Increases metabolic rate, oxygen consumption,
sensitivity to catecholamines
Thyroid replacement - 2
• Thyroxine can precipitate:
– angina
– atrial fibrillation
– heart failure
• Start at low dose and increase slowly
• Monitor treatment with TSH - WHY?
Thyroid hormones
Hypothalamus
TRH
Pituitary
TSH
Negative feedback
Tyrosine
IODINE
Monoiodotyrosine
IODINE
Thyroid
gland
Diiodotyrosine
Thyroxine
replacement
Thyroxine (T4)
T4
Thyroid binding globulin
3,3,5 triiodothyronine
rT3
3,3,5 triiodothyronine
T3
Case 2. 30 year old man
• Weight loss, diarrhoea, palpitations
• On examination
– Hot and sweaty
– Pulse 130bpm, BP 180/80mmHg
• Question
– What is your differential diagnosis?
Investigations
• TSH
<0.1mU/L
• Free T4 40pmol/L
(0.5 - 4)
(12 - 25)
• Do the investigations confirm your
diagnosis?
Thyroid hormones
Hypothalamus
TRH
Pituitary
TSH
Negative feedback
Tyrosine
IODINE
Monoiodotyrosine
IODINE
Thyroid
gland
Diiodotyrosine
Thyroxine (T4)
Hyperthyroid
T4
Thyroid binding globulin
3,3,5 triiodothyronine
rT3
3,3,5 triiodothyronine
T3
Case 2 - continued
• How does your diagnosis explain his
symptoms?
– Weight loss, diarrhoea, tremor, palpitations
• How could you treat this patient?
• What is the quickest way to relieve his
symptoms?
Treatment of hyperthyroidism
• Inhibit production of thyroid hormone by gland
– Thionamines e.g. Carbimazole, propylthiouracil
• Removal of thyroid tissue
– Surgery
– Radioactive iodine
• Treat symptoms
(thyroxine increases sensitivity to catecholamines)
– Beta blockers
Drugs to treat hyperthyroidism
Hypothalamus
TRH
carbimazole
Pituitary
propylthiouracil
TSH
Negative feedback
Tyrosine
IODINE
Monoiodotyrosine
IODINE
Thyroid
gland
Diiodotyrosine
Thyroxine (T4)
Potassium iodide
T4
propylthiouracil
Thyroid binding globulin
3,3,5 triiodothyronine
rT3
3,3,5 triiodothyronine
T3
Carbimazole and propylthiouracil
• Taken orally in once daily dose
• Inhibit production of T3/T4, therefore effect
delayed until existing hormone stores
depleted
• Clinical improvement:
– starts in 1 week
– euthyroid in 6 weeks, stop drug when euthyroid
4-6 months
– 50-70% relapse on stopping drug
Case 3. 48 year old woman
• Known thyrotoxicosis, on carbimazole
• Sore throat 24 hours
• On examination
– Temp. 39oC, pulse 120bpm, inflamed ulcerated
throat, skin rash
• Investigations
– Hb 12g/dl (12-16), wcc 1 x 109/L (4-11),
platelets 180 x 109/L (150 - 400)
• What is the diagnosis?
Adverse effects of thionamines
• Agranulocytosis
– 1 in 1000 treated patients
– may be fatal - infection risk
– reversible on stopping drug
•
•
•
•
Rash
GI upset
Jaundice
Alopecia
Recognition and treatment of
agranulocytosis
• Recognition
– can’t be predicted by monitoring
– warn patient (verbal, leaflet)
• Treatment
– stop drug
– supportive therapy
– treat hyperthyroidism by other means
Case 4. 28 year old woman
• Antenatal clinic appointment, 14 weeks
pregnant. Anxious, palpitations
• On examination
– thin
– pulse 124bpm, BP 170/60mmHg
• Investigations
– TSH < 0.1mU/L, Free T4 36pmol/l (12 - 25)
• What is the diagnosis
• What treatment would you recommend?
Case 4 - continued
• Started on carbimazole
• Asks you
– “what is the risk to my baby if I take this
treatment?”
– “will I be able to breast feed”
• What would you tell her?
Hyperthyroidism in pregnancy
Mother
Baby
Placenta
TRH
TRH
TSH
TSH
Goitre
Thyroid
Thyroid
Carbimazole
T4
T4
Case 5 - 29 year old woman
• Tired all the time
• On the pill, not pregnant
• On examination
– pulse 96, hands cold and sweaty, slight tremor
– small smooth palpable thyroid
• Total T4 180nmol/L (70 - 150)
• TSH 2.7mU/L (0.5 - 4)
• Is she thyrotoxic?
Thyroxine in the plasma
Free thyroxine
Thyroxine
bound to
thyroxinebinding globulin
Some drugs increase thyroxine-binding
globulin and interfere with TFTs
Oestrogens
Clofibrate
Neuroleptics
Free thyroxine
unchanged
Increased bound
thyroxine
(hence total T4
is increased)
Some drugs decrease thyroxine-binding
globulin and interfere with TFTs
Androgens
Adrenocortical
steroids
Free thyroxine
unchanged
Decreased
bound thyroxine
(hence total is
decreased)
Case 5 - continued
• On the pill
• On examination
– pulse 96, hands cold and sweaty, slight tremor
– small smooth palpable thyroid
• Total T4 180nmol/L (70 - 150)
• TSH 2.7mU/L (0.5 - 4)
• If she is not thyrotoxic, how do you explain
her findings?
Case 6. 58 year old man
• Chest pain, short of breath
• Thyrotoxic - treated with carbimazole for 8
months
• No treatment for 6 months
• On examination
– pulse 112bpm, irregularly irregular
– bibasal crepitations
• TSH <0.1mU/L (0.5-4), Free T4 36pmol/L (12-25)
• What has happened?
Radioactive iodine
emits b and some g radiation which
ablates gland
• Concentrated in thyroid gland - hence no ill
effects on rest of body
• Taken orally, physical t1/2 8 days
• Beneficial effect in 1 month, action
maximal after 3 months
•
131I,
Radioactive iodine continued
• Uses
– hyperthyroidism (all ages)
– Thyroid carcinoma or metastases if take up iodine
selectively
• Adverse effects
– Thyroid storm
– Hypothyroidism (6-15% first year, 2-3%pa thereafter)
– No evidence that it causes cancer - but avoid pregnancy
for 6 months after dose
Finally....
• Drugs causing unwanted hyperthyroidism
– amiodarone
– iodine-containing drugs if adenoma/hyperthyroid
• Drugs causing unwanted hypothyroidism
–
–
–
–
amiodarone
sulphonylureas
lithium
iodide - in large doses