Treatment of thyroid disorders

Question 1

What are the abnormalities of Thyroid function ?

Answer 1

Hypothyroidism (‘underachieve’ thyroid)
- Inadequate production and secretion of thyroid hormones (T3 and T4)

Hyperthyroidism (‘overactive’ thyroid)
- Excessive production and secretion of thyroid hormones (T3 and T4)

Question 2

When do we do thyroid function tests (TFT’s)?

Answer 2

Consider performing TFT’s’
- If clinical suspicion of thyroid disease
- Type 1 diabetes or other autoimmune diseases
- New onset atrial fibrillation (cause of hyperthyroid)
- In depression or unexplained anxiety
- Weight changes

Question 3

How do we treat thyroid disorders in general (not medically) ?

Answer 3

Treatment of thyroid disorders;
- Thyroid conditions usually respond well to treatment
- The aim of treatment is to improve symptoms and return thyroid function to within or close to the reference range
- Patients may feel well even when their TFT’s are outside the reference range
- Treatment is usually still recommended for asymptomatic patients with abnormal TFT’s to reduce the risk of long-term complications
- Symptom improvement may lag behind treatment changes (this can take weeks to months)

Question 4

What are the features of Hypothyroidism?

Answer 4

Hypothyroidism;
- Decreased serum free Thyroxine (T4)
- Increased thyroid stimulating hormone (TSH)

• Found approximately in 2-5% of the UK population
• Females are 5 - 10 times more like to be affected than males

Long term complications of hypothyroidism include;
- Cardiovascular disease
- Goitre
- Myxodema coma (very rare but life threatening)

Question 5

What are the features of Subclinical Hypothyroidism?

Answer 5

Subclinical Hypothyroidism;
- Biochemical state where TSH is raised but T3 and T4 are within the reference ranges
- Often detected incidentally although some people may experience symptoms
- Prevalence 4-20%

Long term consequences;
- Increased risk of Cardiovascular mobility and mortality
- Increased risk of fractures and potential links to dementia

Question 6

What are the symptoms of Hypothyroidism?

Answer 6

Symptoms of Hypothyroidism;
- Tiredness
- Weight gain
- Feeling cold
- Constipation
- Dry or thinning hair
- Hoarse voice
- Pins and needles
- Low mood
- Memory problems

Question 7

What are the causes of Hypothyroidism?

Answer 7

Causes of Hypothyroidism;
- Autoimmune thyroiditis - Hashimoto’s
- Congenital
- Iatrogenic (e.g post thyroidectomy or radio-iodine treatment)
- Drug induced (e.g anti-thyroid medications, lithium, amidarone)
- Pituitary disease

Question 8

What are the features of Hasimoto’s?

Answer 8

Hashimoto’s;
- Most common cause of hypothyroidism
- Autoimmune lymphocytes thyroiditis
- An anti body against thyroglobulin is produced or one which has antagonist effects at follicular TSH receptors
- Females > Males

Question 9

How common is Congenital Hypothyroidism (CHT) and the causes?

Answer 9

Congenital Hypothyroidism (CHT);

1 in 2000-3000 babies are born with CHT in the UK (Part of heel prick test in babies)

Causes;
- Absent thyroid (agenesis)
- Under-developed thyroid (dysgenesis) - more common in girls
- Familial enzyme defects (dyshormonogenesis)
- Iodine deficiency
- Intake of goitrogens during pregnancy
- Pituitary defects
- Idiopathic

Question 10

What are the features of Newborns with Congenital Hypothyroidism ?

Answer 10

• May have few or no clinical manifestations of thyroid deficiency
• All babies screened at birth (heel prick test)
• Untreated CHT can result in impaired brain development and low IQ
• If treatment started before the baby is 2-3 weeks old the likelihood of significant longterm problems is low

Question 11

What are the features of Amiodarone?

Answer 11

Amiodarone;
- Amiodarone has a very close structural resemblance to thyroid hormones
- The free base contains 39% iodine by weight, and longterm treatment is associated with 40-fold increase in plasma and urinary iodide levels
- Patients can develop Amiodarone induced hypothyroidism or thyrotoxicosis therefore monitoring of TFT’s is important

Question 12

How do we treat Primary Hypothyroidism?

Answer 12

Treatment Primary Hypothyroidism;
- Levothyroxine (synthetic analogue of thyroxine - T4)

• Do not routinely offer liothyronine for primary hypothyroidism due to lack of evidence
• Natural thyroid extract does not have UK marketing authorisation so safety is unknown
• Staring dose Levothyroxine is 1.6 micrograms/kg of body weight per day (rounded to the nearest 25 micrograms) for adults < 65 years old with primary hypothyroidism and no history of cardiovascular disease (If start at higher dose can exacerbate cardio issues so start low in elderly)
• For patients > 65 years old and adults with history of cardiovascular disease consider starting Levothyroxine at 25 - 50 micrograms per day with titration as higher dose could exacerbate underlying cardiac disease
• Aim to maintain TSH levels within the reference range
• After start or dose check recheck TFT’s after 6 weeks

Question 13

What is the treatment for Subclinical Hypothyroidism ?

Answer 13

Treatment for Subclinical Hypothyroidism;
- Recommendation is to consider Levothyroxine in adults with TSH > 10mU/L on 2 separate occasions 3 months apart

Consider a 6 month trial or Levothyroxine for adults < 65 years old with subclinical hypothyroidism who have:
- A TSH level above the reference range but <10mU/L on 2 separate occasions 3 months apart who are experiencing symptoms of hypothyroidism

Question 14

How should we monitor Hypothyroid patients?

Answer 14

Consider measuring TSH every 3 months until the level has stabilised and then yearly

Question 15

What are the features of Hyperthyroidism ?

Answer 15

Hyperthyroidism;
- Raised T3 and T4 and low TSH
- About 10 times more common in females than males
- Typically affects people ages 20-40 years old

Question 16

What is important to do when considering diagnosing Hyperthyroidism ?

Answer 16

Need to differentiate between Thyrotoxicosis with hyperthyroidism (e.g graves or toxic nodular disease) and thyrotoxicosis without hyperthyroidism (e.g transient thyroiditis ) by;
- Measuring TSH receptor antibodies (TRAbs) to confirm Graves
- Consider technetium scanning of the thyroid gland if TRAbs are negative

Question 17

How would you treat Transient Thyrotoxicosis without Hyperthyroidism?

Answer 17

Treatment of Transient Thyrotoxicosis without Hyperthyroidism;
- Only needs support treatment (e.g beta blockers - Propranolol best options for symptoms of tremor, sweating, palpitations, etc)

Question 18

What are the causes of Hyperthyroidism ?

Answer 18

Causes of Hyperthyroidism;
- Autoimmune - Grave’s disease
- Toxic multi-nodular goitre
- De Quervain’s - (subacute) thyroiditis
- Medication (over-treatment of Levothyroxine)
- Pituitary adenoma (tumour producing excess TSH)
- Transient neonatal thyrotoxicosis (mother with Graves)
- Thyroid adenoma (rare)

Question 19

What are the features of Grave’s disease?

Answer 19

Grave’s Disease;
- Autoimmune disorder mediated by antibodies that stimulate TSH
- Accounts for 60-80% of cases of thyrotoxicosis caused by hyperthyroidism
- Guidelines recommend measuring TSH receptor antibodies (TRAbs) in patients with thyrotoxicosis to confirm Grave’s disease
- Most common in women aged 30-60 years old

Clinical features;
- Diffuse goitre
- Pretibial myxoedema
- Thyroid eyed ease (prominent eyes due to decomposition of myxoedema behind the orbit)
- Arcopachy (swelling of distal digits with overgrown nail plates - different to clubbing)

Question 20

What are the features of Toxic Multinodular Goitre ?

Answer 20

Toxic Multi-nodular Goitre;
- Small benign nodules within the thyroid gland. Cells within the nodules are unresponsive to secretary control mechanisms and secrete excess T3 and T4
- Worldwide, iodine deficiency is the most common cause

Question 21

What are the features of de Quervain’s syndrome?

Answer 21

Subacute thyroiditis;
- Painful swelling of thyroid gland
- Triggered by a viral infection
- Most commonly seen in women aged 20 - 50

Question 22

What are the symptoms of Hyperthyroidism ?

Answer 22

Symptoms of Hyperthyroidism;
- Anxiety
- Palpitations
- Weight loss
- Goitre
- Hair loss
- Fatigue
- Diarrhoea
- Sweating
- Muscle weakness
- Insomnia
- Periods lighter/infrequent

Question 23

How do we treat Hyperthyroidism ?

Answer 23

Treatments of Hyperthyroidism;
- Radioactive iodine
- Anti-thyroid medication
- Symptomatic medication
- Surgery

Important to discuss risk and benefits of all with patient

Question 24

What are the features of Radioactive iodine?

Answer 24

Radioactive iodine;
- Radioactive iodine is given orally and selectively taken up by the thyroid
- Half life of 8 days
- Given as a dose and lasts approximately 2 months
- When administered it is accumulated by follicular cells and as it decays the beta particles emissions destroy surrounding tissue. Since the path length of particles if only 0.5-1mm the damage is restricted to follicular cells
- Usually not suitable before puberty
- Hypothyroidism eventually occurs which can be treated with replacement therapy
- Avoid contact with pregnant women and small children (small risk of radiation)

Question 25

Who would we prescribe Radioactive iodine to?

Answer 25

• Offer as 1st line treatment for Graves disease

Unless;
- Thyroid malignancy is suspected
- The patient is trying to become pregnant or father a child with the next 6 months
- Concerns about compression
- Patient has active thyroid eye disease

Question 26

What are some anti-thyroid drugs and their features?

Answer 26

• Propylthiouracil and Carbimazole (coveted to the active metabolite methimazole) directly inhibit thyroid hormone synthesis
• Reduce synthesis of thyroid hormones by inhibition of thyroperoxidase, thus reducing iodination of thyroglobulin
• Propylthiouracil may also inhibit the conversion of T4 to T3 which occurs in peripheral tissues. This reducing response to already formed T4.

Question 27

What are the features of Carbimazole?

Answer 27

Features of Carbimazole;
- First line choice of anti-thyroid drug in UK

• Effects take several weeks to develop since T4 already in the circulation has a long half life and the thyroid gland has a large store of already formed T3 and T4 which has to be used up
• Usual dose: 15-40mg daily until patient becomes euthyroid (normal function) then reduce to 5-15mg daily
• Therapy usually given for 12-18 months
• Options to use a ‘block and replace’ regimen (high dose carbimazole with levothyroxine (replace)) or titration regimen based on TFT’s

Question 28

What are the Main Side Effects of Carbimazole?

Answer 28

Main Side Effects of Carbimazole;

Neutopenia and agranulocytosis;
- Patients should be advised to report any symptoms or signs suggestive of infection, especially sore throat
- A WBC count should be taken if any clinical evidence of infection
- STOP Carbimazole if Neutopenic (Wouldn’t use antithyroid drugs after that, other treatments)

• Pancreatitis
• Skin rashes
• Increased risk of congenital malformations when used during pregnancy, especially in first trimester at high doses (>15mg daily)
• Women of childbearing age should use effective contraception during treatment with Carbimazole

Question 29

What are the features of Propylthiouracil?

Answer 29

Propylthiouracil;

Consider in patients;
- Who experience side effects with Carbimazole
- Are pregnant or trying to conceive within the following 6 months
- Have a history of pancreatitis

• Usual dose: 200-400mg daily in divided doses until patient becomes euthyroid then reduce to 50-150mg daily in divided doses
• Can be taken when breastfeeding as secreted less than carbimazole since its strongly bound to albumin
• When substituting, carbimazole 1mg is considered equivalent to propylthiouracil 10mg

Question 30

What are the Side Effects of Propylthiouracil?

Answer 30

Side effects:
- Agranulocytosis
- Bone marrow disorders
- Hepatic impairment
- Risk of enhanced effects of Propylthiouracil if given with other medications that compete with binding albumin (e.g other weak acids such as NSAIDs, sulphonamide antibiotics, oral hypoglycaemics, warfarin

Question 31

How should we monitor Antithyroid Medications?

Answer 31

Monitoring Antithyroid Medications;
- TSH, FT4 and FT3 every 6 weeks until TSH within reference range then TSH every 3 months until medications stopped
- STOP and do not restart any antithyroid drugs if person develops agranulocytosis (on blood test)

Question 32

What are some other medications we can use to treat Hyperthyroid patients?

Answer 32

Thyroid hormones increase the number of receptors, particularly B-receptors in various tissues;
- Heart - tachycardia, hypertension and increased risk of dysrhythmias
- Skeletal muscle - temor
- CNS - agitation

Beta Blockers e.g Propanolol often used as an adjunct to anti-thyroid therapy (Wont treat hyperthyroid but treats symptoms causing patient distress)

Question 33

When would we consider Thyroid Surgery?

Answer 33

Patients should be offered total thyroidectomy as first line definitive treatment for Grave’s if;
- There are concerns about compression or
- Thyroid malignancy is suspected or
- Radioactive iodine and anti-thyroid drugs are unsuitable

Question 34

What are the 3 different types of Thyroidectomy ?

Answer 34

3 different types of Thyroidectomy;
- Thyroid lobectomy
- Subtotal thyroidectomy
- Total thyroidectomy

Question 35

What are some potential complications of thyroid surgery ?

Answer 35

Potential complications of thyroid surgery;
- Haemorrhage
- Infection
- Damage to laryngeal nerve
- Hypothyroidism
- Hypocalcaemia
- Hypoparathyroidism