Hyperthyroidism

Question 1

Grave’s disease

Answer 1

• AI
• antibodies bind to and stimulate TSHRs in the thyroid
• causes goitre (smooth)
• hyperthyroidism
• hyperthyroidism causes lid lag

Question 2

What antibodies are there in Grave’s disease?

Answer 2

• antibodies that bind to and stimulate TSHRs in the thyroid
• Other antibodies bind to muscles behind the eye and cause exophthalmos (about a year later)
• Other antibodies cause pretibial myxoedema (hypertrophy)

Question 3

pretibial myxodema

Answer 3

• The swelling (non-pitting) that occurs on the shins of patients with Graves’ disease: growth of soft tissue.
• Not to be confused with myxoedema=hypothyroidism

Question 4

How to diagnose Graves’ disease?

Answer 4

• measuring AB
• scintigram
• examine neck
• examine eyes
• blood test (T4, TSH)

Question 5

Plummers disease

Answer 5

• nodular goitre
• not AI
• Benign adenoma that is overactive at making thyroxine.
• NO pretibial myxoedema
• NO exophthalmos
• scintigram shown hot nodule
• actual thyroid is getting smaller

Question 6

Effects of thyroxine on the SNS

Answer 6

• Sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline.
• Thus there is apparent sympathetic activation
• Tachycardia, palpitations, tremor in hands, lid lag

Question 7

Signs and symptoms of hyperthyroidism

Answer 7

• Weight loss despite increased appetite
• Breathlessness,
• palpitations
• tachycardia
• Sweating
• Heat intolerance
• Diarrhoea
• Lid lag and other sympathetic features

Question 8

Thyroid storm

Answer 8

• life threatening emergency - 50% mortality of untreated

- blood results confirm hyperthyroidism

Question 9

What are the signs and symptoms of thyroid storm?

Answer 9

• Hyperpyrexia > 41C
• accelerated tachycardia / arrhythmia
• cardiac failure
• delirium / frank psychosis
• hepatocellular dysfunction; jaundice

=> needs aggressive treatment

Question 10

What are the treatment options for hyperthyroidism?

Answer 10

• surgery
• radioiodine
• drugs

Question 11

What are the symptoms of viral (de Quervain’s) thyroiditis?

Answer 11

• Painful dysphagia
• Hyperthyroidism
• Pyrexia
• Raised ESR (erythrocyte sedimentation rate)

Question 12

Natural history of viral thyroiditis

Answer 12

• Virus attacks thyroid gland causing pain and tenderness
• Thyroid stops making thyroxine and makes viruses instead
• Thus no iodine uptake (ZERO)

Question 13

Time development of viral thyroiditis?

Answer 13

• Radioiodine uptake zero
• Stored thyroxine released
• Thus toxic with zero uptake
• Four weeks later, stored thyroxine exhausted, so hypothyroid
• After a further month, resolution occurs (like in all viral diseases).
• Patient then becomes euthyroid again.

Question 14

What are the classes of drugs used in treatment of hyperthyroidism?

Answer 14

1. The thionamides (thiourylenes; anti-thyroid drugs)
2. Potassium Iodide
3. Radioiodine
4. β-blockers

-> First 3 reduce production of thyroid hormones, beta-blockers help with the symptoms.

Question 15

What are 2 commonly used thionamides?

Answer 15

= anti thyroid drugs

    - propylthiouracil (PTU)
    - carbimazole (CBZ)

Question 16

What is the clinical use of thionamides?

Answer 16

a) Daily treatment of hyperthyroid conditions
- Graves’
- Toxic Thyroid nodule/toxic multi nodular goitre
b) Treatment prior to surgery
c) reduction of symptoms while waiting for radio iodine to start working.

Question 17

What is the mechanism of action of thionamides?

Answer 17

a) inhibits TPO - hence T3 and T4 synthesis and secretion is inhibited.
b) may suppress antibody production in Graves’ disease
c) reduces conversion of T4 to T3 in peripheral tissues (PTU)

Treatment regimen may include propranolol – rapidly reduces tremor, tachycardia

Question 18

What is the timeframe of the biochemical effect of thionamides?

Answer 18

hours

Question 19

What is the timeframe of the clinical effect of thionamides?

Answer 19

weeks

Question 20

What are some unwanted effects of thionamides?

Answer 20

• agranulocytosis (usually reduction in neutrophils) - rare and reversible on withdrawl of the drug.
• rashes (relatively common)

Question 21

Pharmacodynamics of thionamides

Answer 21

i) orally active
ii) carbimazole is a pro-drug which first has to be converted to methimazole
iii) cross placenta, secreted in breastmilk (PTU

Question 22

How do you follow up on patients taking anti-thyroid drugs?

Answer 22

• Usually aim to stop anti-thyroid drug treatment after 18 months
• Review patient periodically including thyroid function tests for remission/relapse

Question 23

What is the role of beta-blockers in thyrotoxicosis?

Answer 23

• Several weeks for ATDs to have clinical effects eg
  
  • reduced tremor
  • slower heart rate
  • less anxiety
• NON-selective (ie b1 & b2) b-blocker eg propranolol
  achieves these effects in the interim (less so with selective b1 blockers eg atenolol)

Question 24

When is Iodide used?

Answer 24

• usually KI
• doses at least 30x daily requirement
• preparation of hyperthyroid patients for surgery
• severe thyrotoxic crisis (thyroid storm)

Used in patients who are very poorly due to their hyperthyroidism. Only if you need really rapid onset

Question 25

What is the mechanism of action of KI?

Answer 25

- Inhibition of thyroid hormone synthesis & secretion WOLFF–CHAIKOFF effect - presumed autoregulatory effect - inhibits iodination of TG - inhibits H2O2 generation and TPO - hyperthyroid symptoms reduce within 1-2 days - vascularity and size of gland reduce within 10-14 days

Question 26

What are unwanted actions of KI?

Answer 26

Allergic reactions e.g. - rashes - angiooedema - fever

Question 27

Pharmacokinetics of KI

Answer 27

- given orally (Lugol’s solution; aqueous iodine) | - maximum effects after 10 days’ continuous administration

Question 28

How does Radioiodine work?

Answer 28

- accumulates in the colliod | - emits beta particles destroying follicular cells

Question 29

What iodine is used in radio iodine treatment?

Answer 29

I-131 -> high doses

Question 30

What does radioiodine treat?

Answer 30

- hyperthyroidism (Graves, toxic nodular disease) | - thyroid cancer

Question 31

Pharmacokinetics of radioiodine

Answer 31

- Discontinue anti-thyroid drugs 7-10 days prior to radioiodine treatment - Administer as a single oral dose - Graves’ disease: approx 500 MBq - Thyroid cancer: circa 3,000 MBq - Radioactive half life of 8 days - Radioactivity negligible after 2 months

Question 32

radioiodine cautions

Answer 32

- Avoid close contact with small children for several weeks after receiving radioiodine. - Contra-indicated in pregnancy and breast feeding - flush toilet 2x

Question 33

When are low doses of radio iodine used?

Answer 33

- RADIOIODINE 131I or technetium 99 pertechnetate – very low, tracer doses - Tests of thyroid gland pathology eg toxic nodule, thyroiditis vs. Graves’ - Administer i.v. - Negligible cytotoxicity

Question 34

What is propranolol?

Answer 34

non-selective beta blocker

Question 35

Why does KI treatment commit the patients to surgery?

Answer 35

- because the thyroid gland will ultimately become very busy again.

Question 36

What is a normal pulse?

Answer 36

60-100 bpm

Question 37

What kind of oedema occurs in pretibial myxoedema? pitting or non-pitting?

Answer 37

non-pitting oedema on the shins (growth of soft tissue)

Question 38

thionamides

Answer 38

- used to treat hyperthyroidism | - e.g. propylthiouracil, carbimazole

Question 39

phenothiazines

Answer 39

anti-psychotics (dopamine antagonists) -> from another lecture - can cause hyperprolactinaemia