LECTURE 15 - thyroid pharmacology

Question 1

How can you diagnose from tests of thyroid function?

Answer 1

Test serum TSH, serum free T3 and T4 
HYPERthyroidism:
↓ serum TSH
↑ free T4
↑ free T3

HYPOthyroidism:
↑ serum TSH
↓ free T4
↓ free T3

Question 2

How prevalent is hyperthyroidism?

Answer 2

F: 20/1000
M: 2/1000

Question 3

What is the aetiology (causes) of hyperthyroidism?

Answer 3

• Graves’ hyperthyroidism (most common - autoimmune)
• Toxic nodular goitre (single of multinodular)
• Thyroiditis (silent, subacute); inflammation

also caused by

• exogenous iodine
• factitious (taking XS thyroid hormone)
• TSH secreting pituitary adenoma
• neonatal hyperthyroidism

Question 4

What are the signs and symptoms of hyperthyroidism?

Answer 4

Cardiovascular:

• tachycardia
• atrial fibrillation
• shortness of breath
• ankle swelling

Neurological:

• tremor
• myopathy (muscle weakness)
• anxiety

Gastrointestinal:

• weight loss
• diarrhoea
• increased appetite

Eyes/skin:

• sore, gritty eyes
• double vision
• staring eyes
• pruritus (itching)

Question 5

What is Graves’ disease?

Answer 5

• 60-80% of cases of hyperthyroidism
• pathogenic antibodies to TSH receptors on thyroid follicular cells continuously stimulate thyroid gland (Long acting thyroid stimulation)

Question 6

What are the extra-thyroidal manifestations of Graves’ disease?

Answer 6

Eyes

• lid lag/ retraction
• conjunctival oedema (swelling)
• periorbital puffiness (around eye)
• proptosis (bulging)
• ophthalmoplegia (weakness of eye muscles)

Skin

• pretibial myxoedema
• acropachy (swelling of hands and clubbing of fingers)

Question 7

How does neonatal hyperthyroidism arise?

Answer 7

• TSH-R antibodies cross the placenta

- control hyperthyroidism in mother during pregnancy

Question 8

How can you diagnose hyperthyroidism?

Answer 8

• clinical features of Graves’
• consider iodine uptake scan: GD vs thyroiditis
• consider isotope imaging: GD vs TN hyperthyroidism
• optic scans

Question 9

How can you treat hyperthyroidism?

Answer 9

• antithyroid drugs to block hormone synthesis
• surgical removal of thyroid
• radioiodine (131I) therapy

Question 10

How do antithyroid drugs work?

Answer 10

Thionamides

• carbimazole (methimazole)
• propythiouracil: blocks iodine incorporation and organification through inhibition of TPO
• short term preparation of patients for definitive treatment
• induction of remission in Graves’ disease (12-18 months)

Question 11

What are the side effects of thionmaide therapy?

Answer 11

• rapid control, well tolerated
• rash = 5%
• joint pains = 5%
• sickness = 5%
• agranulocytosis: no white blood cells, infection risk, rare = 1:1000 or less
• liver disease with propylthiouracil
  Low cure rate: 30-40% (lower in men)

Question 12

How can you treat hyperthyroidism with surgery?

Answer 12

• used frequently
• pre-treatment with antithyroid drugs
  Indications:
• large goitre (especially if suspicion of co-existing thyroid cancer)
• pregnancy
• pronounced ophthalmology
• patient preference

Question 13

How is iodine-131 used to treat hyperthyroidism?

Answer 13

• capsule (fixed dose)
• highly effective (85% cure)
• usually pre-treatment with drugs
• may worsen eye disease (steroids)

Risks

• hypothyroidism (~60%)
• cancer and infertility (however no proof of this)
• teratogenesis (contra-indicated in pregnant and breastfeeding)

Question 14

How prevalent is hypothyroidism?

Answer 14

F: 40/1000

5% of over 60s

Question 15

What is the aetiology of hypothyroidism?

Answer 15

• autoimmune = Hashimoto’s thyroiditis (TPO and Tg antibodies - genetic predisposition)
• after treatment of hyperthyroidism
• subacute/ silent thyroiditis
• iodine deficiency (main source from milk and dairy, major cause)
• congenital (thyroid agenesis/ enzyme defects)

Question 16

What are the signs and symptoms of hypothyroidism?

Answer 16

Cardiovascular:

• bradycardia
• heart failure
• pericardial effusion (fluid around the heart)

Neurological:

• depression
• psychosis
• carpal tunnel syndrome

Gastrointestinal

• weight gain
• constipation

Skin:

• myxoedema
• rash on legs
• vitiligo

Question 17

How can hypothyroidism be treated?

Answer 17

• 3rd most prescribed medication in UK

- 23 million tablets of levothyroxine prescribed

Question 18

How prevalent is goitre?

Answer 18

• Palpable goitre: 8.6% (F: 12.1%, M: 4.5%)

- Visible goitre: 6.9%

Question 19

What are thyroid nodules?

Answer 19

• most common in women (4:1) and older populations
• increased on areas of low iodine intake
• may cause thyroid dysfunction or compression
• prevalence of malignancy = 4-6.5%
• malignancy risk in incidentalomas remain controversial

Question 20

How prevalent are nodules?

Answer 20

• high resolution ultrasound = 50-67%
• autopsy = 50% of population
• lifetime risk for developing nodule = 10%

Question 21

What clinical features are associated with increased risk of malignancy?

Answer 21

• age <20 or >60
• firmness of noodle
• rapid growth
• fixation to adjacent structures
• vocal cord paralysis
• regional lymphadenopathy
• history of neck irradiation
• family history of thyroid cancer
  BUT thyroid cancer is very rare

Question 22

How do you investigate thyroid nodules/ goitre?

Answer 22

1. Assessment of thyroid function
   - serum TSH
   - serum free T4, serum free T3
   - thyroid antibodies
2. Assessment of thyroid size
   - symptoms
   - X-ray thoracic inlet
   - CT or MRI of neck
   - respiratory flow loop
3. Assessment of thyroid pathology
   - radionuclide scanning
   - ultrasound scanning
   - fine needles aspiration cytology

Question 23

What is the role of ultrasound scanning?

Answer 23

• differentiation from cystic nodules
• differentiation of single from multiple nodules (superior to palpation)
• criteria suggestive of malignancy (irregular margin, calcifications, solid, increased blood flow)
• guidance of fine needle aspiration

Question 24

What are the different types of thyroid cancer?

Answer 24

Differentiated cancers (from follicular cells)

• papillary carcinoma (72-85%)
• follicular carcinoma (10-20%
• anaplastic carcinoma (<1%)

From C-cells
- medulla carcinoma (1.7-3%)

Aetiology

• external irradiation
• iodine deficiency
• oncogene expression
• genetic factors (medullary Ca - MEN)

Question 25

How can you manage differentiated thyroid cancer?

Answer 25

• surgery is first attempt
• radioactive iodine - higher dose given to suppress TSH
• in rare cases radio/chemo therapy given