10-11-23 - Treatment of thyroid disorders

Question 1

Learning outcomes

Answer 1

• Understand the causes of hypothyroidism and hyperthyroidism
• Know how hypothyroidism is treated
• Know the treatment options for hyperthyroidism
• Understand the mechanism of action and side effects of directly acting anti-thyroid drugs
• Know the clinical uses of thyroid acting drugs

Question 2

What are the 2 abnormalities of thyroid function?

What is T3 and T4?

Answer 2

• 2 abnormalities of thyroid function:

1) Hypothyroidism (‘underactive’ thyroid)
* Inadequate production and secretion of thyroid hormones (T3 and T4)

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

• T3 Triiodothyronine
• T4 Thyroxine

Question 3

What are 5 Indications for performing thyroid function tests (TFT’s)?

Answer 3

• 5 Indications for performing thyroid function tests (TFT’s):

1) If there is a clinical suspicion of thyroid disease

2) Type 1 diabetes or other autoimmune diseases

3) New onset atrial fibrillation

4) In depression or unexplained anxiety

5) Weight changes

Question 4

How well do thyroid conditions respond to treatment?

What is the aim of treatment?

Can patients feel fine with abnormal TFTs?

Why is treatment usually still recommended for asymptomatic patients with abnormal TFT’s?

What can symptom improvement lag behind?

Answer 4

• 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 5

How are hormones affected in hypothyroidism?

How common is it in the UK?

Which groups are more likely to be affected?

What are 3 Long term complications of hypothyroidism?

Answer 5

• Hypothyroidism
• Decreased serum free thyroxine (T4)
• Increased thyroid stimulating hormone (TSH)
• Found in approximately 2-5% of the UK population
• Females are 5-10 times more likely to be affected than males
• 3 Long term complications of hypothyroidism:

1) Cardiovascular disease

2) Goitre

3) Myxoedema coma (very rare but life-threatening condition)
* multiple organ abnormalities associated with altered sensorium

Question 6

What is subclinical hypothyroidism?

How is it often detected?

What is its prevalence?

What are 3 Long term consequences of subclinical hypothyroidism?

Answer 6

• Subclinical hypothyroidism is a biochemical state where TSH is raised but T3 and T4 are within the reference range
• It is often detected incidentally although some people may experience symptoms
• Prevalence is 4-20% (proportion of a particular population found to be affected by a medical condition at a specific time)
• 3 Long term consequences of subclinical hypothyroidism:
  1) Increased cardiovascular morbidity and mortality
  2) Increased risk of fractures
  3) Potential links to dementia

Question 7

What are 9 symptoms of hypothyroidism?

Answer 7

• 9 symptoms of hypothyroidism:
  1) Tiredness
  2) Weight gain
  3) Feeling cold
  4) Constipation
  5) Dry or thinning hair
  6) Hoarse voice
  7) Pins and needles
  8) Low mood
  9) Memory problems

Question 8

What are 5 causes of hypothyroidism?

Answer 8

• 5 causes of hypothyroidism:

1) Autoimmune thyroiditis (Hashimoto’s)
* Most common cause

2) Congenital

3) Iatrogenic (e.g. post thyroidectomy or radio-iodine treatment)

4) Drug induced (e.g. anti-thyroid medications, lithium, amiodarone)

5) Pituitary disease

Question 9

What is Hashimoto’s thyroiditis the most common cause of?

What type of disorder is Hashimoto’s thyroiditis?

What groups is it most common in?

Answer 9

• Hashimoto’s thyroiditis is the most common cause of hypothyroidism
• Hashimoto’s thyroiditis is an autoimmune disorder which results in the destruction of thyroid cells
• It is more common in females between ages 30-50

Question 10

How common is Congenital hypothyroidism (CHT) in the UK?

What are 7 causes of CHT?

Answer 10

• 1 in 2000-3000 babies are born with CHT in the UK
• 7 causes of CHT:
  1) Absent thyroid (agenesis)
  2) Under-developed thyroid (dysgenesis) – more common in girls
  3) Familial enzyme defects (dyshormonogenesis)
  4) Iodine deficiency
  5) Intake of goitrogens during pregnancy
  6) Pituitary defects
  7) Idiopathic

Question 11

How can newborns with CHT present?

How are babies screened at birth for CHT?

What can untreated CHT lead to?

What can early treatment prevent?

Answer 11

• Newborns with CHT may have few or no clinical manifestations of thyroid deficiency
• All babies are screened at birth for CHT (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 long-term problems is low

Question 12

What does amiodarone have a close structural resemblance to?

What can patients develop when taking amiodarone?

Answer 12

• Amiodarone has a very close structural resemblance to thyroid hormones
• Patients can develop amiodarone induced hypothyroidism or thyrotoxicosis therefore monitoring of TFT’s is important

Question 13

What is the first line Treatment of primary hypothyroidism?

What is not offered?

Answer 13

• Levothyroxine (synthetic analogue of thyroxine) is first line treatment for primary hypothyroidism
• We do not routinely offer liothyronine for primary hypothyroidism due to lack of evidence

Question 14

What is the starting dose of levothyroxine for <65 years old with primary hypothyroidism and no history of cardiovascular disease?

What is the starting dose of levothyroxine for >65 years old and adults with a history of cardiovascular disease?

What is the aim of this treatment?

How often should TSH be measured?

Answer 14

• Starting dose of levothyroxine for primary hypothyroidism is 1.6 micrograms/kg of body weight per day (rounded to the nearest 25 micrograms)
• For adults >65 years old and adults with a 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 when treating primary hypothyroidism with levothyroxine
• Consider measuring TSH every 3 months until the level has stabilised ( 2 similar measurements within the reference range 3 months apart) and then once a year.

Question 15

What is the treatment for subclinical hypothyroidism?

What is an exception to this?

Answer 15

• Subclinical hypothyroidism treatment:
• Recommendation is to consider levothyroxine in adults with TSH >10mU/L on 2 separate occasions 3 months apart
• Consider a six-month trial of levothyroxine for adults <65 years old with subclinical hypothyroidism who have:
• A TSH level above the reference range but <10 mU/L on two separate
  occasions 3 months apart and who are experiencing symptoms of
  hypothyroidism

Question 16

How are hormones affected in hyperthyroidism?

What groups is it more common in?

Answer 16

• In hyperthyroidism, there is Raised T3 and T4 and low TSH
• It is more common in females that are 20-40 years olds (About 10 times more common in females than males)

Question 17

What is the difference between thyrotoxicosis and hyperthyroidism?

How can we Differentiate between thyrotoxicosis with hyperthyroidism (eg Graves’ or toxic nodular disease) and thyrotoxicosis without hyperthyroidism (eg transient thyroiditis)?

Answer 17

• Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source.
• We differentiate between thyrotoxicosis with hyperthyroidism (eg Graves’ or toxic nodular disease) and thyrotoxicosis without hyperthyroidism (eg transient thyroiditis) by:

1) Measuring TSH receptor antiboides (TRAbs) to confirm Graves’ disease

2) Consider technetium scanning of the thyroid gland if TRAbs negative

Question 18

How is transient thyrotoxicosis without hyperthyroidism treated?

What should be given to hyperthyroidism patients who are waiting for specialist assessment and further treatment?

Answer 18

• Transient (temporary) thyrotoxicosis without hyperthyroidism (e.g from being unwell) usually only needs supportive treatment eg b-blockers, such as propanolol for tachycardia
• Consider antithyroid drugs along with supportive treatment for adults with hyperthyroidism who are waiting for specialist assessment and further treatment

Question 19

What are 11 symptoms of hyperthyroidism?

Answer 19

• 11 symptoms of hyperthyroidism:
  1) Anxiety
  2) Palpitations
  3) Weight loss
  4) Goitre
  5) Hair loss
  6) Fatigue
  7) Diarrhoea
  8) Sweating
  9) Muscle weakness
  10) Insomnia
  11) Periods lighter/infrequent

Question 20

What are 7 causes of hyperthyroidism?

Answer 20

• 7 causes of hyperthyroidism:

1) Autoimmune – Graves’ disease (most common)

2) Toxic multinodular goitre – causes thyroid to work too much

3) de Quervain’s – (subacute) thyroiditis

4) Medication (overtreatment with levothyroxine)

5) Pituitary adenoma (tumour producing excess TSH)

6) Transient neonatal thyrotoxicosis (mother with Graves’)

7) Thyroid adenoma (rare)

Question 21

What type of disorder is Graves’ disease?

What % of cases of thyrotoxicosis caused by hyperthyroidism does Graves’ account for?

How can Graves’ disease be confirmed?

What groups is it most common in?

What are 4 clinical features of Graves’ disease?

Answer 21

• Autoimmune disorder mediated by antibodies that behave like 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 Graves’ disease
• Most common in women aged 30-60 years old
• 4 clinical features of Garves’ disease:

1) Diffuse goitre

2) Pretibial myxoedema
* Pretibial myxedema is a skin condition that causes plaques of thick, scaly skin and swelling of your lower legs

3) Thyroid eye disease (prominent eyes due to deposition of myxoedema behind the orbit)

4) Acropachy (swelling of distal digits with overgrown nail plates)

Question 22

What is a toxic multinodular goitre?

How do cells in nodules differ from regular cells?

What is the most common cause of toxic multinodular goitre worldwide?

Answer 22

• Toxic multinodular goitres are small benign nodules within the thyroid gland.
• Cells within the nodules are unresponsive to secretory control mechanisms and secrete excess T3 and T4
• Worldwide, iodine deficiency is the most common cause

Question 23

What is de Quervain’s (subacute thyroiditis)?

What is it triggered by?

What groups is it most common in?

Answer 23

• de Quervain’s (subacute thyroiditis) is painful swelling of the thyroid gland
• It is triggered by a viral infection
• Most commonly seen in women aged 20-50

Question 24

What are 4 treatment options for hyperthyroidism?

Answer 24

• 4 treatment options for hyperthyroidism:
  1) Radioactive iodine
  2) Anti-thyroid medication
  3) Symptomatic medication
  4) Surgery
• Important to discuss risks and benefits of all options with patients

Question 25

NICE Guideline ‘Thyroid disease: assessment and management’ (in picture)

Answer 25

Question 26

How is radioactive iodine administered?

What is its half-life?

How long does a dose last?

Describe where radioiodine accumulates.

How is damage restricted to follicular cells?

What can eventually occur from this treatment?

Who is radioiodine not suitable for?

Answer 26

• Radioiodine (133I) is given orally and selectively taken up by the thyroid
• Half-life of 8 days
• Given as a single dose and lasts approximately 2 months
• When administered it is accumulated by the follicular cells and as it decays the beta particles emissions destroy surrounding tissue.
• Since the path length of the particles if only 0.5-1mm the damage is restricted to the follicular cells
• Hypothyroidism eventually occurs which can be treated with replacement therapy
• Usually not suitable before puberty
• Avoid contact with pregnant women and small children

Question 28

What is radioiodine the first line of treatment for?

What are 5 contraindications for radioiodine use in Graves’?

Answer 28

• Radioiodine is offered as 1st line definitive treatment for Graves’ disease
• 5 contraindications for radioiodine use in Graves’:

1) Anti thyroid medications are likely to achieve remission

2) Thyroid malignancy is suspected

3) The patient is trying to become pregnant or father a child with the next 6 months

4) Concerns about compression

5) Patient has active thyroid eye disease

Question 29

What are 2 examples of thioureylenes used as anti-thyroid drugs?

What is there mechanism of action?

Answer 29

• 2 examples of thioureylenes used as anti-thyroid drugs:
  1) Propylthiouracil
  2) Carbimazole
• They are converted to the active metabolite methimazole, which directly inhibits thyroid hormone synthesis
• Reduce the 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, thus reducing response to already formed T4

Question 30

What should be done before commencing anti-thyroid drugs?

What should be offered when offering antithyroid drugs as first line definitive treatment to adults with Graves’ disease?

Answer 30

• Before commencing antithyroid drugs check full blood count (FBC) and liver function tests (LFT’s)
• When offering antithyroid drugs as first line definitive treatment to adults with Graves’ disease offer carbimazole for 12 to 18 months using either a block and replace or a titration regimen

Question 31

What is carbimazole the first line drug for?

How long do its effects take?

What is the usually dose given?

How long does carbimazole therapy last?

What options for treatment are available based on TFTs?

Answer 31

• Carbimazole is the 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 carbimazole dose is 15-40mg daily until patient becomes euthyroid then reduced to 5-15mg daily
• Carbimazole therapy usually given for 12-18 months
• Options to use a ‘block and replace’ regimen (high dose carbimazole with levothyroxine) or a titration regimen based on TFT’s

Question 32

What are the 3 main side-effects of carbimazole?

When should carbimazole be stopped?

What is the MHRA advice (Drug Safety Update, February 2019) for carbimazole in pregnant women?

Answer 32

• 3 main side-effects of carbimazole:

1) Neutropenia (low neutrophils) and agranulocytosis (low granulocytes)
* Patients should be advised to report any symptoms or signs suggestive of infection, especially sore throat (need to see a doctor in this case)
* A white blood cell count (full blood count - FBC) should be taken if any clinical evidence of infection
* STOP carbimazole if neutropenic

2) Pancreatitis

3) Skin rashes

• MHRA advice (Drug Safety Update, February 2019):
• Increased risk of congenital malformations when used during pregnancy especially in first trimester and at high doses (>15mg daily).
• Women of childbearing age should use effective contraception during treatment with carbimazole

Question 33

In what 3 types of patients should Propylthiouracil be used as an antithyroid drug?

What is the usual dose for Propylthiouracil?

What are 3 side-effects of Propylthiouracil?

Answer 33

• 3 types of patients should Propylthiouracil be used as an antithyroid drug:

1) Patients who experience adverse reactions to carbimazole

2) Patients that are pregnant or trying to conceive within the following 6 months

3) Patient that have a history of pancreatitis

• Usual dose (don’t memorise, as we will have BNF in practise):
• 200-400mg daily in divided doses until patient becomes euthyroid then reduce to 50-150mg daily in divided doses
• 3 side-effects of Propylthiouracil:
  1) Agranulocytosis
  2) Bone marrow disorders
  3) Hepatic impairment

Question 34

Why can Propylthiouracil be used when breastfeeding?

When is there a risk of enhanced effects of propylthiouracil?

What are the equivalent doses for carbimazole and Propylthiouracil?

Answer 34

• Propylthiouracil can be taken when breastfeeding as secreted less than carbimazole since it is strongly bound to albumin
• Risk of enhanced effects of propylthiouracil if given with other medications that compete with binding to albumin e.g. other weak acids such as NSAID’s, sulphonamide antibiotics, oral hypoglycaemics, warfarin
• When substituting, carbimazole 1mg is considered equivalent to propylthiouracil 10mg

Question 35

Describe the monitoring of antithyroid medications.

When should antithyroid medications be stopped?

Answer 35

• Monitoring of 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 a person develops agranulocytosis

Question 36

What do thyroid hormones increase the number of?

What 3 tissues do thyroid hormones increase the number of B-receptors in?

What can this lead to in each tissue?

What medications can be used as an adjunct to antithyroid therapy?

Answer 36

• Thyroid hormones increase the number of receptors, particularly β-receptors in various tissues
• 3 tissues thyroid hormones increase the number of B-receptors in:

1) Heart
* Can lead to tachycardia, hypertension and increased risk dysrhythmias

2) Skeletal muscle
* Tremor

3) CNS
* Agitation

• β-blockers e.g. propranolol often used as an adjunct to anti-thyroid therapy

Question 37

What are 3 times Patients should be offered a total thyroidectomy as first line definitive treatment for Graves’?

Answer 37

• 3 times Patients should be offered a total thyroidectomy as first line definitive treatment for Graves’:

1) There are concerns about compression or

2) Thyroid malignancy is suspected or

3) Radioactive iodine and anti-thyroid drugs are unsuitable

Question 38

Thyroid lobectomy, subtotal thyroidectomy, total thyroidectomy (in picture)

Answer 38

Question 39

What are 6 Potential complications of thyroid surgery?

Answer 39

• 6 Potential complications of thyroid surgery:
  1) Haemorrhage
  2) Infection
  3) Damage to laryngeal nerve
  4) Hypothyroidism
  5) Hypocalcaemia
  6) Hypoparathyroidism