Hyperthyroidism & Graves Disease

Question 1

What is the definition of hyperthyroidism?

Answer 1

an over-production of thyroid hormone by the thyroid gland

hyperthyroidism is also sometimes called thyrotoxicosis

Question 2

What is the definition of thyrotoxicosis?

Answer 2

an abnormal and excessive quantity of thyroid hormone in the body

Question 3

What is the difference between primary and secondary hyperthyroidism?

Answer 3

primary:
* this is due to thyroid pathology

• the thyroid gland is producing excessive levels of thyroid hormone

secondary:
* the thyroid is producing excessive thyroid hormone as a result of overstimulation by TSH

• the pathology is within the hypothalamus or pituitary gland

Question 4

What is Grave’s disease and how does it produce symptoms?

Answer 4

• an autoimmune condition in which TSH receptor antibodies cause a primary hyperthyroidism
• TSH receptor antibodies are produced by the immune system
• they mimic TSH and stimulate TSH receptors on the thyroid

this is the most common cause of hyperthyroidism

Question 5

What is toxic multinodular goitre (Plummer’s disease) and how does it cause symptoms?

Answer 5

• multiple nodules develop on the thyroid gland
• the nodules all act independently of each other and the normal feedback system
• they continuously produce excessive thyroid hormone

Question 6

What is meant by exopthalmos?

Why does it occur?

Answer 6

• the bulging of the eyeball out of the socket caused by Grave’s disease
• due to inflammation, swelling and hypertrophy of the tissue behind the eyeball

Question 7

What is meant by pretibial myxoedema and why does it occur?

Answer 7

• there are deposits of mucin under the skin on the anterior aspect of the leg
• this produces a discoloured, waxy, oedematous appearance
• it is specific to Grave’s disease and is a reaction to TSH receptor antibodies

Question 8

Who is typically affected by Grave’s disease?

Answer 8

women aged 30 - 50

Question 9

What are the 4 main causes of hyperthyroidism?

Answer 9

• Grave’s disease
• toxic multinodular goitre
• solitary toxic thyroid nodule
• thyroiditis (e.g. Hashimoto’s / De Quervain’s)

Question 10

What are the universal features of hyperthyroidism?

Answer 10

• sweating / heat intolerance
• tachycardia
• frequent loose stools
• sexual dysfunction
• fatigue
• weight loss
• anxiety / irritability
• oligomenorrhea

Question 11

What features of hyperthyroidism are specific to Grave’s disease?

Answer 11

• diffuse goitre (without nodules)
• bilateral exophthalmos
• pretibial myxoedema
• thyroid acropachy

Question 12

What is thyroid acropachy?

Answer 12

a triad of:

• digital clubbing
• soft tissue swelling of the hands and feet
• periosteal new bone formation

this occurs in < 1% patients with Grave’s disease

Question 13

What features are unique to toxic multinodular goitre?

Who tends to be affected?

Answer 13

• most patients are aged > 50
• goitre with many firm nodules

this is the second most common cause of hyperthyroidism

Question 14

What is a solitary toxic thyroid nodule?

Answer 14

• there is a single abnormal thyroid nodule that acts alone to release thyroid hormone
• usually a benign adenoma
• treated with surgical removal of the nodule

Question 15

What are the features of De Quervain’s thyroiditis?

Answer 15

there is a presentation of a viral infection with:

• fever
• neck pain + tenderness
• dysphagia
• features of hyperthyroidism

Question 16

What is the course of De Quervain’s thyroiditis typically like?

Answer 16

• initially there is a hyperthyroid phase
• TSH levels fall due to negative feedback
• this results in a subsequent hypothyroid phase

Question 17

What is the treatment for De Quervain’s thyroiditis?

Answer 17

• the condition is self-limiting
• supportive treatment with NSAIDs for pain / inflammation
• beta-blockers may be given for symptomatic relief of hyperthyroidism

Question 18

What is meant by “thyroid storm”?

Answer 18

• a rare and more severe presentation of hyperthyroidism
• it presents with pyrexia, tachycardia and delirium

this is life-threatening if not treated

Question 19

How is thyroid storm managed?

Answer 19

• patient needs admission for monitoring
• it is treated in the same way as any other presentation of thyrotoxicosis
• supportive care with IV fluids, beta-blockers and antiarrhythmic medications may be required

Question 20

Why does thyroid storm occur?

Answer 20

it occurs as a result of uncontrolled hyperthyroidism due to a major stress:

• infection
• trauma
• untreated / undertreated hyperthyroidism
• PE / CHF
• severe emotional distress
• DKA
• stroke

Question 21

What is the first line treatment for hyperthryoidism (including Grave’s disease)?

Answer 21

carbimazole 40mg

• euthyroidism is typically achieved after 4-8 weeks
• the patient is then given a maintenance dose of carbimazole

Question 22

When giving the maintenance dose of carbimazole, what 2 methods can be used for titration?

Answer 22

“titration-block”:
* the dose of carbimazole is titrated down from 40mg gradually to maintain euthyroidism

block-and-replace:
* a dose is given that is sufficient to block all thyroid hormone production

• the patient is given levothyroxine which is titrated to effect

Question 23

How long must a patient take carbimazole for?

Answer 23

complete remission and the ability to stop taking carbimazole is usually achieved within 18 months

block and replace treatments tend to last for 6-9 months

Question 24

What is the main side effect associated with carbimazole?

Answer 24

agranulocytosis

• a deficiency of granulocytes (i.e. neutrophils) in the blood
• this results in increased vulnerability to infection

Question 25

What is the second-line treatment for hyperthyroidism?

Answer 25

**propylthiouracil** * used in a similar way to carbimazole * small risk of **severe hepatic reactions**, including death ## Footnote carbimazole is preffered due to risk of severe hepatic reactions

Question 26

How can radioactive iodine be used to treat hyperthyroidism?

Answer 26

* a single dose of radioactive iodine is drunk * the radiation **destroys a portion of cells** within the thyroid * the reduction in functioning cells results in **decreased thyroid hormone production** ## Footnote this is usually used when patients relapse after ATD treatment or are resistant to it

Question 27

What are the drawbacks of using radioactive iodine?

Answer 27

* remission can take **up to 6 months** * patients can be left **hypothyroid** afterwards and require **levothyroxine replacement**

Question 28

What are the rules that are in place when radioactive iodine treatment is used?

Answer 28

* must **not be pregnant** or get pregnant within **6 months** * must be **> 16 years** * must avoid contact with **children / pregnant women** for **3 weeks** after * must avoid contact with anyone for several days after

Question 29

When are beta-blockers used for the management of hyperthyroidism?

Answer 29

* used for **symptomatic relief** of adrenaline-related symptoms * **propanolol** is preffered as it is **non-selective** * treat the symptoms whilst the underlying treatment takes time to work * particularly useful in **thyroid storm**

Question 30

What is the only definitive treatment option for hyperthyroidism?

Answer 30

* **surgery** to remove the whole thyroid or any toxic nodules * the patient will be left **hypothyroid** as **thyroid hormone production is stopped** * they require **life-long levothyroxine** replacement

Question 31

What drugs can cause hyperthyroidism?

Answer 31

amiodarone

Question 32

What would you expect to see on TFTs in hyperthyroidism?

Answer 32

* low TSH * high levels of T4 and T3 | this is in primary hyperthyroidism

Question 33

What are the 4 phases of De Quervain's thyroiditis?

Answer 33

**phase 1:** * hyperthyroidism, painful goitre, raised ESR * lasts 3-6 weeks **phase 2:** * euthyroid for 1-3 weekw **phase 3:** * hypothyroid for weeks - months **phase 4:** * thyroid structure / function returns to normal

Question 34

What investigation can be performed in De Quervain's thyroiditis?

Answer 34

**thyroid scintigraphy** * shows globally reduced uptake of iodine-131

Question 35

What can rarely cause thyrotoxicosis in patients with pre-existing thyroid disease?

Answer 35

**contrast** * patients with pre-existing thyrotoxicosis should **not receive iodinated contrast** * this results in a large iodine load to the thyroid and **hyperthyroidism developing over 2-12 weeks**

Question 36

What is meant by thyroid eye disease and why does it occur?

Answer 36

* there is an **autoimmune response** to an autoantigen (TSH receptor) * this results in **retro-orbital inflammation** * inflammation results in **glycosaminoglycan and collagen deposition** in the muscles ## Footnote this affects 25-50% of patients with Grave's disease

Question 37

What risk factors increase the likelihood of thyroid eye disease?

Answer 37

* **smoking** is the most important modifiable RF * **radioiodine treatment** may increase inflammatory symptoms (prednisolone reduces risk)

Question 38

What are the features of thyroid eye disease?

Answer 38

* exophthalmos * conjunctival oedema * optic disc swelling * ophthalmoplegia * inability to close the eyelids results in **sore, dry eyes** if this is untreated, there is a risk of **exposure keratopathy** ## Footnote patients may be hypo-, eu- or hyperthyroid at time of presentation

Question 39

What is exposure keratopathy?

Answer 39

**damage to the cornea** that occurs from **prolonged exposure** of the ocular surface to the **outside environment** * can lead to ***ulceration***, ***keratitis*** and ***permanent vision loss*** from scarring

Question 40

What is involved in the management of thyroid eye disease?

Answer 40

* **topical lubricants** prevent corneal inflammation caused by exposure * **steroids (prednisolone)** * radiotherapy * surgery

Question 41

For patients with established thyroid eye disease, what red flag symptoms prompt urgent review by an opthalmologist?

Answer 41

* unexplained **deterioration in vision** * obvious **corneal opacity** * **cornea still visible** when eyes are closed * disc swelling * history of **globe subluxation** (eye suddenly popping out) * awareness of change in intensity or quality of **colour vision**