Hyperthyroidism

Question 1

List 3 causes of hyperthyroidism

Answer 1

1. Grave’s
2. Plummer’s disease
3. Viral thyroiditis (De Quervain’s syndrome)

Question 2

Outline the pathophysiology of Grave’s disease

Answer 2

• Autoimmune disease - antibodies bind TSH receptors in the thyroid - this makes the thyroid overactive becuase there is loads of antibodies stimulating the TSH receptors

Question 3

List symptoms of Graves’ disease and group some symptoms with an explanation for the physiology behind this grouping

Answer 3

Due to increased NA / A sensitivity:

• Tremor
• Rapid pulse
• Palpitations
• Tachycardia
• Lid lag - adrenaline tries to keep eyelids open

Due to raised BMR:

• Feel hot
• Weight loss

Autoimmune attack:

• Exopthalmos
• Pretibial myxoedema
• Chemosis (red, angry looking eyes)

Question 4

5 investigations to diagnose Grave’s, including 1 visual presentation?

Answer 4

1. ↑ fT4 (free T4)
2. ↓ TSH (as -ve feedback from high T4)
3. Measure anti-TSHR antibodies
4. Scintigram - evenly hot
5. Smooth goitre (visual) - due to whole gland involvement

Question 5

1) Pathophysiology of Plummer’s disease?
2) How does this different pathophysiology of Plummer’s disease cause difference in some symptoms to Grave’s - i.e. how do symptoms vary than those in Grave’s and why?

Answer 5

1)

• Benign adenoma that is overactive at thyroid production
• Toxic nodular goitre
• Non-tumour bit is hypoplastic due to T4 from tumour bit inhibiting TSH so non-tumour bit slows T4 production

2)

• It is not an autoimmune disease like Grave’s so there are no autoimmune symptoms such as
• No pretibial myxoedema
• No exopthalmos

Question 6

4 investigations to diagnose Plummer’s disease, including visual presentations?

Answer 6

1. ↑ fT4 (free T4)
2. ↓ TSH (as -ve feedback from T4)
3. Scintigram - hot nodule where toxic nodular goitre is and rest of thyroid gland is not visible due to hypoplasia
4. Visible nodular or multinodular (NOT smoothly enlarged) goitres

Question 7

1) Effect of T4 on SNS and associated symptoms?
2) Why does lid lag occur?

Answer 7

1)

• Thyroxine increases sensitivity of adrenoreceptors to NA / A
• Palpitations, tremor, tachycardia, lid lag

2)

• Muscles supplying eye supplied by both SNS and oculomotor nerve that keeps the eye open (levator palpebrae superioris). So increasing SNS sensitivity, the eye will open so lid lag occurs

Question 8

1) What is a thyrotoxic crisis / thyroid storm?
2) Signs and symptoms?
3) Treatment?

Answer 8

1)

• MEDICAL EMERGENCY complication of hyperthyroidism

2)

• Hyperpyrexia
• Accelerated tachycardia / dysrhythmia
• Cardiac failure
• Delirium / psychosis
• Hepatocellular dysfunction, jaundice

3)

• Surgery (thyroidectomy)
• Radioiodine
• Drugs (thionamides, KI, Beta-blockers)

Question 9

1) Name 2 thionamides
2) When are these thionamides used to treat hyperthyroidism?

Answer 9

1)

1. Carbimazole (this is the prodrug → methimazole is active drug)
2. PTU (propylthiouracil)

2)

• Daily treatment of hyperthyroid conditions - grave’s, plummer’s
• To control hyperthyroidism before thyroidectomy because you don’t want to give general anaesthetic to someone who is tachycardic with labile heart rate
• Following slow-acting radioiodene treatment

Question 10

1) Mechanism of action of thionamides and action timeline?
2) Main unwanted action of thionamides?

Answer 10

1)

1. INHIBITS TPO

• Thereby inhibiting the iodination of tyrosine residues in TG and inhibiting coupling of MIT / DITs
• So reduction of T3 / T4 synthesis BUT still stored thyroxine in colloid so delayed action - takes weeks

2. SUPPRESSES ANTI-TSHR ANTIBODIES IN GRAVE’S
3. IMPAIRS PERIPHERAL T4 → T3 deiodination (PTU in particular does this)

2)

• Agranulocytosis

Question 11

1) How are thionamides administered?
2) What is the half-life of thionamides?

Answer 11

1)

Orally

2)

6-15 hrs

Question 12

What consideration must you make when prescribing thionamides to pregnant women?

Answer 12

• They crosss the placenta and are also secreted in breast milk
• Therefore you must lower the dose to prevent hypothyroidism in the foetus
• PTU secreted less in breast milk so give PTU preferentially rather than carbimazole

Question 13

When is iodine treatment (KI) administered?

Answer 13

• In combination with other drugs
• Preparation of hyperthyroid patients for surgery as it reduces size and vascularity of the thyroid
• In cases of severe thyrotoxic crisis

Question 14

What is the mechanism of action of KI treatment?

Answer 14

• WOLF-CHAIKOFF EFFECT = ‘the temporary reduction in thyroid hormones following ingestion of large amounts of iodine

1. Inhibits H₂O₂ generation
2. Inhibits iodination of TG

Question 15

What unwanted actions can KI treatment have?

Answer 15

• Rashes
• Fever
• Angioedema

Question 16

In what form is KI treatment administered and what is it called?

Answer 16

• Orally
• Lugol’s solution or aqueous iodine

Question 17

1) Mechanism of action of radioiodene?
2) Considerations before administering radioiodene in terms of other drugs?
3) Cautions of radioiodene?

Answer 17

1)

• Radioiodene is taken up and eventually into the colloid, from here it emits beta-particles, destroying follicular cells

2)

• Discontinue anti-thyroid drugs such as thionamides and KI 7-10 days prior to radioiodene treatment so the thyroid is still active so takes up loads of iodene (loads of radioiodene) which can then maximally destroy follicular cells of the thyroid gland

3)

• Avoid close contact with small children for weeks
• Ensure you tell patient they’ll still be radioactive for a few months - airport security

Question 18

1)

Pathophysiology of viral thyroiditis (De Quervain’s syndrome)?

2)

Signs and symptoms of viral thyroiditis?

Answer 18

1)

• Virus attacks the thyroid gland, damaging the thyroid follicles → all stored thyroxine is released → so initial hyperthyroidism, then hypothyroidism
• Thyroid is also inactive so no further production of thyroxine

2)

• Painful dsyphagia
• Pyrexia
• Malaise
• Tender, palpable, unilaterally enlarged thyroid
• Pain radiating to ear
• ↑ Raised ESR

Question 19

How does viral thyroiditis appear on a scintigram and why?

Answer 19

• Invisible
• Because the thyroid is inactive due to viral attack
• There is therefore no iodine uptake so thyroid is invisible on the scintigram

Question 20

How is viral thyroiditis (De Quervain’s syndrome) treated?

Answer 20

• No specific treatment necesssary
• After a while (roughly a month), the stored thyroxine is exhausted and inactive thyroid follicular cells recover so patient becomes euthyroid

Question 21

1) What type of beta-blockers are used in managing hyperthyroidism?
2) Give a named example
3) Why are these types of beta-blockers useful?

Answer 21

1)

• Non-selective beta-blocker

2)

• Propanolol

3)

• Non-selective so widespread effect to combat actions all over the body

Question 22

Summarise what findings you would see and explain why they are like this in a scintigram with …

1) Grave’s disease
2) Plummer’s disease
3) Viral thyroiditis (De Quervain’s syndrome)

Answer 22

1)

• Evenly hot scintigram across whole thyroid gland
• Due to autoimmune attack across whole of thyroid

2)

• Hot nodules on scintigram - not even
• Due to benign ademona soaking up all the iodine as it is hyperactive
• Whereas the hypoplastic sections do not soak up any or much iodine so it doesn’t appear on the scintigram, so the appearance is of hot nodule(s)

3)

• Invisible
• Due to completely inactive thyroid follicular cells after being damaged by virus