Therapeutics of Thyroid Disease

Question 1

Where is the thyroid gland located?

Answer 1

In the neck region, on the anterior surface of the trachea, just below the larynx

Question 2

What hormone does the Hypothalamus produce?

Answer 2

TRH - thyroid releasing hormone

Question 3

What hormone does the pituitary produce?

Answer 3

TSH - thyroid stimulating hormone

Question 4

What hormones do the thyroid gland produce?

Answer 4

T3 (liothyronine - MOST ACTIVE) and T4 (levothyroxine - given to people as treatment)

Question 5

What does T4 go on to produce?

Answer 5

rT3 and T3

Question 6

What is primary thyroid disease?

Answer 6

(most common), when there is an issue with the thyroid itself, so T3 and T4 are not produced

Question 7

What is secondary thyroid disease?

Answer 7

Issue in the pituitary and TSH is not produced (usually due to a series of other endocrine diseases)

Question 8

What is tertiary thyroid disease?

Answer 8

A hypothalamic disorder with no hormones being produced (at the top of the chain)

Question 9

What is hypothyroidism?

Answer 9

Decreased production of thyroid hormones at the level of the thyroid gland (more common in women)

Question 10

What are the causes of Hypothyroidism?

Answer 10

• Autoimmune disease (hashimotos’s thyroiditis)
• result of previous treatment (ie surgery) - removal of thyroid
• Iodine imbalance (uncommon in UK) - we have iodine in flour
• Congenital hypothyroidism - child born without thyroid

Question 11

What are the symptoms of hypothyroidism?

Answer 11

• Lethargy, weakness
• Dry scaly skin
• Sensitive to cold weather
• Depression
• Hair loss
• Memory loss
• Weight gain
• Constipation
• Puffy face and gruff voice with untreated disease

Question 12

What do Thyroid Function Tests (TFTs) look at?

Answer 12

• Thyroid Stimulating Hormone (TSH)
• Free (unbound) T4
• Thyroid peroxidase antibody (rarely measured outside secondary care) – as it is an autoimmune disease

Question 13

What levels of TSH and T4 are there in patients with primary hypothyroidism?

Answer 13

Increased TSH and decreased unbound T4 in the blood (pituitary still producing TSH as they want to try to stimulate T4)

Question 14

How are raised TSH levels treated?

Answer 14

Treated with lifelong T4

Question 15

What antibody is tested for in primary hypothyroidism?

Answer 15

TPO

Question 16

What is the initial treatment for adults under 50 yrs?

Answer 16

initially 50-100 mcg thyroxine daily, adjusted 25–50 mcg every 3–4 weeks according to response

Question 17

What is the initial treatment for adults over 50 and in heart disease?

Answer 17

initially 25 mcg once daily, adjusted 25 mcg every 4 weeks
If you rush in and give too higher a dose of T4 then you can cause heart disease or make their heart disease worse, this is why we gradually increase

Question 18

What is the initial treatment for congenital hypothyroidism?

Answer 18

initially 10-15 mcg/kg for neonates (max 50 mcg), adjusted 5 mcg/kg every 2 weeks. Start this from 6-7 days old, they are then taking it for the rest of their life. As they are part of the physical and mental development they are often on higher doses to ensure development

Question 19

When should TSH be measured during congenital hypothyroidism?

Answer 19

after 8-12 weeks (T½ of T4 = 7days) and three monthly until stabilised – as a child they may measure the levels more frequently to start with

Question 20

What is the usual maintenance dose for adults and children with hypothyroidism?

Answer 20

• 100-200 mcg adults

* 50-200 mcg children, depending on age

Question 21

How often is TSH monitored in hypothyroidism?

Answer 21

• Monitor TSH yearly for adults and every 4-6 months until puberty for children; aim for
  * Lower half of reference range – upper limit is 4 so you want 0.5-2 as an aim
  * Symptom free

Question 22

What combination treatments for hypothyroidism are available?

Answer 22

Liothyronine and levothyroxine (although evidence shows no benefit over monotherapy)

Question 23

What patient counselling is needed for hypothyroidism treatment?

Answer 23

• Life-long treatment
• Single daily dose
• Do not take at same time as calcium or iron preparations or caffeine containing beverages – as it affects the absorptions
• Three strengths of tablet – common cause of confusion, they all look exactly the same usually generic
• Need for monitoring
• Entitled to medical exemption certificate for prescription charges – if you have autoimmune disease, congenital hypothyroidism.

Question 24

What is hyperthyroidism?

Answer 24

• Autoimmune (Grave’s disease)
• Toxic Nodules
• Antibodies to TSH receptor stimulate the gland
• INCREASED production of thyroid hormones
• Prevalence of 2% in women & 0.2% in men

Question 25

What symptoms are present with hyperthyroidism?

Answer 25

* Anxiety * Palpitations * Tremor * Weight loss – relatively quickly without trying * Tachycardia * Goitre * Heat intolerance * Warm moist skin * Difficulty sleeping * Diarrhoea (symptoms are similar to cancer)

Question 26

What levels of TSH and T4 are observed in hyperthyroidism?

Answer 26

DECREASED TSH and INCREASED T4 as pituitary thinks there is lots of T4 and stops producing TSH

Question 27

What is there a low risk of in the treatment for hyperthyroidism?

Answer 27

Long term HYPOthyroidism - affecting the production of T3 and T4 rather than affecting the gland

Question 28

What groups are thionamides preferred for?

Answer 28

* Children * Pregnancy, breast feeding (propylthiouracil only) * Uncomplicated, mild disease * Acute phase, prior to surgery or radioactive iodine

Question 29

What is the first choice drug for hyperthyroidism?

Answer 29

Carbimazole: interferes with thyroid hormone synthesis by inhibiting thyroperoxidase activity in follicular lumen

Question 30

What doses are used for carbimazole?

Answer 30

* Start with 15-40 mg daily (depends on severity of symptoms – can be higher) * Start treatment quickly as severe cardiac symptoms which you want to treat * Maintain until TFTs normal (4-8 weeks) * Maintenance for 12-18 months * decrease by 25-30% monthly, until 5-15mg. reduce dose to have balance whilst treating symptoms and having lowest dose possible * Longer-term treatment may be required if relapse – occurs in up to 50% of patients with non-mild disease

Question 31

What risk is carbimazole associated with?

Answer 31

An increased risk of congenital malformations when used during pregnancy. Women of a childbearing age should use effective contraception during treatment. Should only be considered during pregnancy at lowest effective dose with additional monitoring

Question 32

What is the blocking-replacement regimen?

Answer 32

* Carbimazole 40-60 mg for approx 4 weeks – until the body has got rid of all their T3 and T4 they have * THEN Carbimazole 40-60 mg PLUS thyroxine 50-100 mcg * Makes patient temporarily hypothyroid * Not eligible for free prescriptions * Treat for up to 18 months * Thyroid gland returns to normal function when stop treatment * Not in pregnancy as only carbimazole crosses the placental barrier so you completely stop the babies thyroid production and they will have nothing to replace this – causing developmental issues

Question 33

What drug can be used in hyperthyroidism if the patient is intolerant to carbimazole?

Answer 33

Propylthoiuracil: 200-400mg daily initially in divided doses - 50mg TDS maintenance - preferred in pregnancy

Question 34

What is drug induced agranulocytosis?

Answer 34

- linked to carbimazole - Can cause bone marrow suppression - decreased white cell count, leading to infection

Question 35

What patient counselling is needed for carbimazole and Propylthiouracil?

Answer 35

- single daily dose for carbimazole, divided doses for Propylthiouracil - Report signs of agranulocytosis: sore throat, mouth ulcer, bruising - Report signs of hepatic dysfunction with Propylthiouracil: pruritis, jaundice, dark urine - Advise on contraception if on carbimazole - Need for regular review, tests - Patients with hyperthyroidism ARE NOT entitled to medical exemption certificate for prescription charges

Question 36

What other treatment options are available for hyperthyroidism?

Answer 36

Radioactive Iodine and surgery

Question 37

What are the characteristics of radioactive iodine?

Answer 37

``` – Non-invasive – Excellent cure rate – Likelihood of long term hypothyroidism – Can worsen eye disease – Avoid pregnancy/fatherhood ```

Question 38

What is radioactive iodine preferred for?

Answer 38

``` – First-line treatment except for mild disease or if radioactivity means is unsuitable – Failure to respond to drug treatment – Relapse after drugs – Comorbid cardiac disease – Toxic nodular goitre ```

Question 39

What are the pros and cons of surgery for hyperthyroidism?

Answer 39

– Excellent and rapid cure rate – High likelihood of long term hypothyroidism – Invasive – Risk of damage to parathyroid gland – Scarring and possible swallowing difficulties

Question 40

What is surgery preferred for in hyperthyroidism?

Answer 40

– Oesophageal obstruction – Intolerance to drug treatment – Young adults

Question 41

What needs to be considered before using radioactive iodine or surgery for hyperthyroidism?

Answer 41

• Do not use either of these immediately after diagnosis • Make patient euthyroid first using drugs for several weeks • Prevent thyrotoxic crisis (thyroid storm) due to dangerously high levels of T4 released into system – Hyperpyrexia, dehydration. – Heart rate greater than 140 beats per minute, hypotension – Nausea, vomiting, diarrhoea, abdominal pain. – Confusion, agitation, delirium, psychosis, seizures or coma

Question 42

What is adjuvant (additional) therapy in hyperthyroidism?

Answer 42

Beta-blockade: • rapid relief of symptoms within 4 days: palpitations, anxiety, tremor • C/I in asthma • Propranolol, nadolol • May need to be given 3-4 times per day as metabolism increased in hyperthyroidism • Usually only needed for initial stages of treatment, when still symptomatic

Question 43

What drugs can induce Thyroid disease?

Answer 43

Iodine, Amiodarone, Lithium

Question 44

How can Iodine cause drug-induced thyroid disease?

Answer 44

* Overdose e.g. Radiographic contrast media * Acute - inhibits release of T3/T4 from thyroid * Prolonged – suppress T3/T4 production * Rarely, can cause thyrotoxicosis if there is an underlying defect in autoregulation * Iodine deficiency (very rare in UK) can cause hypothyroidism due to inability to produce T3/T4

Question 45

How can amiodarone create drug-induced thyroid disease?

Answer 45

* Contains organic iodine * Hypothyroidism * Can occur at anytime in treatment – 1-10% of patients * Inhibition of synthesis & release of T4 & T3 * usually continue amiodarone and start replacement T4 therapy if necessary * Mild Hyperthyroidism * Blocks conversion of T4 to T3, therefore increases TSH & T4 * Transient when start treatment – normalises in 3-4 months * Severe hyperthyroidism * Increased production of T4 because of iodine content * Direct thyroiditis – excessive release of T4 into circulation * Withdraw therapy, if possible or may use carbimazole

Question 46

How does lithium create drug-induced thyroid disease?

Answer 46

* Hypothyroidism * inhibits iodine uptake and prevents T3 & T4 release * can be transient & subclinical * monitor TSH * start replacement T4 therapy if clinical * Hyperthyroidism * Rare, paradoxical effect