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 (0.5 - 4)

• Free T4 5pmol/L (12-25pmol/L)

• Cholesterol 8.5mmol/l (desirable <5.2)

• Question– How do you explain these results?

Thyroid hormones

Tyrosine

Monoiodotyrosine

Diiodotyrosine

Thyroxine (T4)

3,3,5 triiodothyroninerT3

3,3,5 triiodothyronineT3

Thyroid gland

IODINE

IODINE

Thyroid binding globulin

T4

Negative feedbackHypothalamus

PituitaryTRH

TSH

Hypothyroid

Stored as thyroglobulin

in thyroid gland

• How would you treat this condition?

• How quickly would you expect the treatment to work?

• What precautions would you take when starting treatment?

Questions

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

Tyrosine

Monoiodotyrosine

Diiodotyrosine

Thyroxine (T4)

3,3,5 triiodothyroninerT3

3,3,5 triiodothyronineT3

Thyroid gland

IODINE

IODINE

Thyroid binding globulin

T4

Negative feedbackHypothalamus

PituitaryTRH

TSH

Thyroxine replacement

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 (0.5 - 4)

• Free T4 40pmol/L (12 - 25)

• Do the investigations confirm your diagnosis?

Thyroid hormones

Tyrosine

Monoiodotyrosine

Diiodotyrosine

Thyroxine (T4)

3,3,5 triiodothyroninerT3

3,3,5 triiodothyronineT3

Thyroid gland

IODINE

IODINE

Thyroid binding globulin

T4

Negative feedbackHypothalamus

PituitaryTRH

TSH

Hyperthyroid

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

Tyrosine

Monoiodotyrosine

Diiodotyrosine

Thyroxine (T4)

3,3,5 triiodothyroninerT3

3,3,5 triiodothyronineT3

Thyroid gland

IODINE

IODINE

Thyroid binding globulin

T4

Negative feedbackHypothalamus

PituitaryTRH

TSH

carbimazole propylthiouracil

propylthiouracilPotassium iodide

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 pregnancyMother Baby

TRH

TSH

T4

Thyroid

TRH

TSH

T4

Thyroid

Carbimazole

Placenta

Goitre

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 plasmaFree thyroxine

Thyroxine bound to

thyroxine-binding globulin

Some drugs increase thyroxine-binding globulin and interfere with TFTs

Free thyroxine unchanged

Increased bound thyroxine

(hence total T4 is increased)

Oestrogens Clofibrate Neuroleptics

Free thyroxine unchanged

Decreased bound thyroxine (hence total is

decreased)

Androgens Adrenocortical steroids

Some drugs decrease thyroxine-binding globulin and interfere with TFTs

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

• 131I, emits and some 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

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