LECTURE 15 - thyroid pharmacology Flashcards
How can you diagnose from tests of thyroid function?
Test serum TSH, serum free T3 and T4 HYPERthyroidism: ↓ serum TSH ↑ free T4 ↑ free T3
HYPOthyroidism:
↑ serum TSH
↓ free T4
↓ free T3
How prevalent is hyperthyroidism?
F: 20/1000
M: 2/1000
What is the aetiology (causes) of hyperthyroidism?
- 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
What are the signs and symptoms of hyperthyroidism?
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)
What is Graves’ disease?
- 60-80% of cases of hyperthyroidism
- pathogenic antibodies to TSH receptors on thyroid follicular cells continuously stimulate thyroid gland (Long acting thyroid stimulation)
What are the extra-thyroidal manifestations of Graves’ disease?
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)
How does neonatal hyperthyroidism arise?
- TSH-R antibodies cross the placenta
- control hyperthyroidism in mother during pregnancy
How can you diagnose hyperthyroidism?
- clinical features of Graves’
- consider iodine uptake scan: GD vs thyroiditis
- consider isotope imaging: GD vs TN hyperthyroidism
- optic scans
How can you treat hyperthyroidism?
- antithyroid drugs to block hormone synthesis
- surgical removal of thyroid
- radioiodine (131I) therapy
How do antithyroid drugs work?
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)
What are the side effects of thionmaide therapy?
- 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)
How can you treat hyperthyroidism with surgery?
- used frequently
- pre-treatment with antithyroid drugs
Indications: - large goitre (especially if suspicion of co-existing thyroid cancer)
- pregnancy
- pronounced ophthalmology
- patient preference
How is iodine-131 used to treat hyperthyroidism?
- 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)
How prevalent is hypothyroidism?
F: 40/1000
5% of over 60s
What is the aetiology of hypothyroidism?
- 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)
What are the signs and symptoms of hypothyroidism?
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
How can hypothyroidism be treated?
- 3rd most prescribed medication in UK
- 23 million tablets of levothyroxine prescribed
How prevalent is goitre?
- Palpable goitre: 8.6% (F: 12.1%, M: 4.5%)
- Visible goitre: 6.9%
What are thyroid nodules?
- 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
How prevalent are nodules?
- high resolution ultrasound = 50-67%
- autopsy = 50% of population
- lifetime risk for developing nodule = 10%
What clinical features are associated with increased risk of malignancy?
- 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
How do you investigate thyroid nodules/ goitre?
- Assessment of thyroid function
- serum TSH
- serum free T4, serum free T3
- thyroid antibodies - Assessment of thyroid size
- symptoms
- X-ray thoracic inlet
- CT or MRI of neck
- respiratory flow loop - Assessment of thyroid pathology
- radionuclide scanning
- ultrasound scanning
- fine needles aspiration cytology
What is the role of ultrasound scanning?
- 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
What are the different types of thyroid cancer?
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)
How can you manage differentiated thyroid cancer?
- surgery is first attempt
- radioactive iodine - higher dose given to suppress TSH
- in rare cases radio/chemo therapy given
