Thyroid disease

Question 1

1) What happens in hyperthyroidism?

2) What is the difference between hyperthyroidism and thyrotoxicosis?

Answer 1

1) Metabolic activity is increased to such an extent that it becomes pathological.
2) Hyperthyroidism = increased synthesis of T3 and T4. Thyrotoxicosis = increased levels of T3 and T4 in circulation.

Question 2

Describe the impact of hyperthyroidism on the thyroid negative feedback mechanism.

Answer 2

Elevated levels of T3 and T4 negatively feedback to the hypothalamus and anterior pituitary, reducing the levels of TRH and TSH which are produced and released.

Question 3

Describe the 2 groups that causes of hyperthyroidism can be categorised into.

Answer 3

1) Increased thyroid hormone synthesis (there is normal or increased radio iodine uptake).
2) No increased thyroid hormone synthesis (there is near absent radio iodine uptake).

Question 4

Name 8 causes of hyperthyroidism and state which is the most common.

Answer 4

Grave's disease (most common)
Toxic multinodular goitre/ toxic adenoma
Gestational hyperthyroidism
Pituitary adenoma
Iodine excess
De Quervain's thyroiditis
Thyroid hormone ingestion
Ectopic hormone production

Question 5

1) What is Grave’s disease?
2) In whom is Grave’s disease more common?
3) Which autoantibodies are present in and diagnostic of Grave’s disease?

Answer 5

1) An autoimmune disorder caused by the presence of autoantibodies to TSH receptors.
2) Women, usually onset is between 20 and 40.
3) TSI antibodies (can also be circulating IgG autoantibodies present which are produced by B cells).

Question 6

Describe the basic pathophysiology behind Grave’s disease.

Answer 6

Autoantibodies stimulate and activate the TSH receptor.
This increases thyroglobulin and iodine in the colloid, causing increased T3 and T4.
This means that there is more T3 and T4 bound to thyroid binding globulin in circulation.

Question 7

1) How can Grave’s disease be distinguished clinically from other causes of hyperthyroidism?
2) What other autoimmune conditions can Grave’s disease be associated with?
3) What type of thyroid enlargement occurs in patients with Grave’s disease?
4) Give 3 triggers for the onset of Grave’s disease.

Answer 7

1) By ocular changes such as exophthalmos and other signs such as pretibial myxoedema.
2) Pernicious anaemia, T1DM, Addison’s disease and Vitiligo.
3) Smooth thyroid enlargement.
4) Stress, infection and childbirth.

Question 8

Describe the basic pathophysiology behind toxic multinodular goitre/ toxic adenoma.

Answer 8

Genetic mutations can cause development of an abnormal TSH receptor.
The mutated receptor becomes autonomous and can activate by itself in the presence or absence of TSH.
This means that more T3 and T4 are produced to enter circulation, causing hyperthyroidism.

Question 9

1) How common is toxic multinodular goitre (toxic adenoma) as a cause of hyperthyroidism?
2) Who is this most common in?
3) If there is a single enlarged thyroid nodule, what is this more suggestive of?

Answer 9

1) 2nd most common cause of hyperthyroidism.
2) The elderly (increased risk with increasing age), more common in females and in iodine deficient areas.
3) cysts, adenomas, a discrete nodule in MNG or a malignancy.

**10% of solitary thyroid nodules are neoplastic in origin.

Question 10

Describe what happens in gestational hyperthyroidism.

Answer 10

In pregnancy, high levels of hCG can cross react with TSH receptors, causing a physiological increase in thyroid hormone synthesis.

Question 11

How can a pituitary adenoma cause hyperthyroidism?

Answer 11

Rarely, pituitary tumours can autonomously secrete TSH. Tumours can be malignant or benign but both can cause increases in TSH production which leads to increased activation of the TSH receptor, resulting in more T3 and T4 being produced and therefore more in circulation.

Question 12

How can hyperthyroidism occur through ectopic hormone production?

Answer 12

If thyroid cancer metastasises to elsewhere, then metastases can begin to produce and release the thyroid hormones T3 and T4.

Question 13

How can hyperthyroidism be caused through thyroid hormone ingestion?

Answer 13

Factitious ingestion of thyroid hormones or overdose on levothyroxine. This is because thyroid hormones are absorbed easily in the gut and can enter circulation easily.

Question 14

What happens to cause hyperthyroidism in cases of iodine excess?

Answer 14

This is a rare endogenous cause where increased iodine levels shift production to produce more thyroid hormone.

Question 15

1) What can hyperthyroidism as a result of iodine excess be caused by?
2) What can be seen biochemically if hyperthyroidism is caused by levothyroxine excess?

Answer 15

1) Food contamination or contrast media (these can cause a thyroid storm if a patient is already hyperthyroid).
2) Increased T4, decreased T3 and decreased thyroglobulin.

Question 16

1) What is De Quervain’s thyroiditis?

2) What is the basic pathophysiology in De Quervain’s thyroiditis?

Answer 16

1) Inflammation of the thyroid gland.
2) Inflammation can cause follicular cells to be destroyed, releasing T3 and T4 into the blood stream, resulting in hyperthyroidism.

Question 17

Describe the main causes of De Quervain’s thyroiditis.

Answer 17

Usually develops after an infection, and normally causes a painful goitre.

Can also be caused by radiation and certain types of medication.

Question 18

1) How is De Quervain’s thyroiditis usually treated?

2) Describe 3 potential diagnostic features of De Quervain’s thyroiditis.

Answer 18

1) The condition is usually self-limiting and management is with NSAIDs.
2) Increased temperature, increased ESR, low isotope uptake on a scan.

Question 19

1) In cells, what happens to T4?
2) What are the actions of T3 within body cells?
3) What do all causes of hyperthyroidism result in?
4) What clinical manifestations occur as a result of an increased cellular metabolic rate in hyperthyroidism?

Answer 19

1) It is converted to T3.
2) Speeds up the cell’s basal metabolic rate, causing the cell to produce more proteins and burn more energy.
3) Excessive thyroid hormones and a hyper metabolic state.
4) Increased cardiac output, stimulation of bone resorption and activation of the SNS.

Question 20

1) Why do patients with hyperthyroidism experience weight loss with increased appetite?
2) Why do patients with hyperthyroidism experience heat intolerance?
3) Name 5 presenting features that can be associated with hyperthyroidism as a result of the activation of the sympathetic nervous system.

Answer 20

1) Due to an increased basal metabolic rate (**there is paradoxical weight gain in 10%)
2) Due to an increased basal metabolic rate causing increased heat production.
3) Rapid heart rate (fast/ irregular - AF/AVT), sweating, hyperactivity, anxiety, insomnia.

Question 21

Aside from weight loss, heat intolerance and effects of the sympathetic nervous system, name 5 other signs or symptoms of hyperthyroidism.

Answer 21

Oligomenorrhoea ± infertility
Labile emotions
Brisk reflexes 
Fine tremor
Palmar erythema
Thin hair
Lid lag
Lid retraction
Goitre ± bruit/ thyroid nodules

Question 22

State 3 signs or symptoms of hyperthyroidism which are more indicative of Grave’s disease.

Answer 22

1) Exopthalmos/ ophthalmoplegia
2) Pretibial Myxoedema
3) Thyroid acropachy (digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation).

Question 23

1) What is lid lag?
2) What is lid retraction?
3) What two long term conditions is a patient with long term ongoing hyperthyroidism?

Answer 23

1) when the eyelid lags behind the eye’s descent as a patient watches a finger descend.
2) exposure of the sclera above the iris, causing a ‘stare’.
3) CHF and osteoporosis.

Question 24

1) What percentage of patients with Grave’s disease are affected by thyroid eye disease?
2) What does thyroid eye disease cause?
3) What conditions are involved in thyroid eye disease?

Answer 24

1) 20-50%
2) Eye discomfort, grittiness, increased tear production, photophobia and diplopia.
3) Exopthalmos/ proptosis, conjunctival oedema, corneal ulceration, corneal ulceration, ophthalmoplegia, papilloedema and loss of colour revision.

Question 25

1) What is a thyroid storm?
2) When might a thyroid storm occur?
3) What happens in a thyroid storm?

Answer 25

1) A life threatening complication of hyperthyroidism where there is a state of severe hyper metabolism.
2) When a patient stops their medication, develops an infection or has surgery.
3) All normal symptoms of hyperthyroidism are exaggerated (heat intolerance becomes a high fever, tachycardia becomes an arrhythmia).

Question 26

How is a diagnosis of hyperthyroidism initially investigated and then confirmed?

Answer 26

TFTs. Overt hyperthyroidism = low TSH, high T3 and T4. Subclinical hyperthyroidism = low TSH, normal T3 and T4.

If abnormal results are found, repeat again 3 months after to confirm diagnosis.

Question 27

Which additional blood tests might you consider in a patient with suspected hyperthyroidism?

Answer 27

FBC: may be normocytic anaemia and mild neutropenia in a patient with Grave’s disease/
ESR/ CRP: may be elevated in thyroiditis.
Thyroid autoantibodies:

**FBC and LFTs need to be checked if antithyroid drugs are to be started.

Question 28

What radiological investigations might you consider in a patient with suspected hyperthyroidism?

Answer 28

USS: of thyroid/ nodules if malignancy suspected.
Isotope scan: to assess for hot/ cold nodules and to determine the cause of the disorder.

**Fine needle aspiration may be required if malignancy suspected.

Question 29

1) How might symptom control of hyperthyroidism be managed medically?
2) What antithyroid drugs are available?

Answer 29

1) Beta blockers, eye drops (aim to taper and stop beta blocker once patient is euthyroid).
2) Carbimazole (1st line) and Prophylthiouracil.

Question 30

When are antithyroid drugs used and what are the aims of treatment with them?

Answer 30

1) Short-term to restore euthyroidism in preparation for definitive treatment.
2) Medium-term with the aim of inducing remission of Graves’ disease.
3) Long-term if radioactive iodine treatment or surgery is contraindicated or declined.

Question 31

1) What is often first line definitive treatment for patients with hyperthyroidism?
2) In whom is radio iodine treatment contraindicated?

Answer 31

1) Radioactive iodine treatment which induces damage of DNA leading to death of thyroid cells.
2) People with Graves’ disease with active or severe orbitopathy (as it can cause exacerbation) AND pregnancy or women planning to become pregnant in the next 4–6 months as it crosses the placenta and can cause severe hypothyroidism in the foetus AND breastfeeding mothers.

**close and prolonged contact with children and pregnant women should be avoided for about three weeks after standard-dose radioiodine treatment.

Question 32

1) What are surgical options for patients with hyperthyroidism?
2) What pre-operative treatment will be required before total or partial thyroidectomy and why?
3) What can post operative complications include?

Answer 32

1) Total thyroidectomy, or hemithyroidectomy for a single thyroid nodule.
2) Antithyroid drugs aiming for euthyroidism as this reduces the risk of thyrotoxic crisis which may be precipitated by surgery.
3) Hypothyroidism, hypocalcaemia due to hypoparathyroidism (often transient), and vocal cord paresis due to damage to the recurrent laryngeal nerve.

Question 33

1) What is hypothyroidism and when does it occur?
2) What two chronic conditions can hypothyroidism cause if it is not treated?
3) Describe the onset of hypothyroidism.

Answer 33

1) Inadequate output of thyroid hormones by the thyroid gland and occurs when there is too little thyroid hormone circulating in the body.
2) Heart disease and dementia.
3) Insidious, usually occurring in women >40.

**Hypothyroidism is relatively common: 4/1000/yr.

Question 34

Name 4 causes of primary hypothyroidism.

Answer 34

1) Hashimoto’s thyroiditis.
2) Iodine deficiency
3) Treatment for hyperthyroidism
4) Medications (i.e. Lithium, Amiodarone)

Question 35

Name 4 causes of secondary hypothyroidism.

Answer 35

1) Pituitary tumours
2) Sheehan’s syndrome (pituitary necrosis; often happens after childbirth)
3) Radiation therapy to pituitary gland
4) Infections

Question 36

1) What is secondary hypothyroidism?
2) What is the most common cause of hypothyroidism in the developed world?
3) What is the most common cause of hypothyroidism in the developing world?

Answer 36

1) Where the pituitary gland fails to produce sufficient TSH. Often associated with hypopituitarism and lack of other pituitary hormones such as ACTH.
2) Hashimoto’s thyroiditis.
3) Iodine deficiency

**Iodine deficiency is the most common cause in the developing world and worldwide.

Question 37

1) Describe Hashimoto’s thyroiditis.
2) What are the effects of Hashimoto’s thyroiditis on the thyroid gland?
3) Who is Hashimoto’s thyroiditis more common in?

Answer 37

1) Autoimmune inflammation of the thyroid gland. Associated with antithyroid peroxidase (anti-TPO) antibodies and with anti-thyroglobulin antibodies. Patients can be hypothyroid or euthyroid on presentation.
2) Initially causes a goitre due to lymphocytic and plasma cell infiltration, but later there is atrophy of the thyroid gland.
3) More common in women aged 60-70.

Question 38

1) Why does iodine deficiency cause hypothyroidism?
2) Which treatments for hyperthyroidism can lead to resultant hypothyroidism?
3) How can Lithium cause hypothyroidism?

Answer 38

1) Because Iodine is essential for the production of thyroid hormones.
2) Carbimazole, Prophylthiouracil, radioactive iodine and thyroid surgery.
3) Lithium inhibits production of thyroid hormones in the thyroid gland.

Question 39

What are the effects of Amiodarone on the thyroid gland?

Answer 39

Amiodarone is an iodine rich drug, structurally like T4 which interferes with thyroid hormone production and metabolism. It usually can cause hypothyroidism through inhibition of T4 release, but has been known to cause thyrotoxicosis as well.

**2% patients taking Amiodarone will get significant thyroid disease.

Question 40

Give 10 features which can be associated with the clinical presentation of hypothyroidism.

Answer 40

Weight gain
Fatigue/ tiredness/ sleepiness
Dry skin
Coarse hair/ hair loss
Fluid retention (oedema/ pleural effusion/ ascites)
Amenorrhoea
Constipation
Cold skin/ cold intolerance
Depression/ low mood
Hoarse voice
Poor memory
Myalgia/ myopathy
Neuropathy
Goitre

Question 41

Name the 11 signs of hypothyroidism.

Answer 41

Bradycardia
Reflexes relax slowly
Ataxia
Dry, thin hair and skin
Yawning, drowsiness, coma
Cold hands/ skin
Ascites ± non-pitting oedema
Round, puffy face/ double chin
Defeated demeanour/ depression
Immobile ± ileum
CCF

**The mnemonic ‘BRADCYCARDIC’ can be used to remember these.

Question 42

Describe what features may also occur in clinical presentation of secondary hypothyroidism.

Answer 42

There may be clinical features of primary hypothyroidism together with clinical features of possible hypothalamic-pituitary disease such as recurrent headache, diplopia, and/or visual field defects.

Could also be features associated with hypopituitarism.

Question 43

What TFT findings would suggest primary hypothyroidism?

Answer 43

High TSH

Low T4

Question 44

What TFT findings would suggest subclinical hypothyroidism?

Answer 44

High TSH

Normal T4

Question 45

What TFT findings would suggest secondary hypothyroidism?

Answer 45

Normal or low TSH

Low t4

Question 46

Aside from TFTs, what other blood tests might you consider in a patient with suspected hypothyroidism?

Answer 46

FBC & B12: assess for possible pernicious anaemia.
HbA1c: assess for T1DM.
Coeliac serology: assess for coeliac disease.
Serum lipids: assess for associated Dyslipidaemia.
Cholesterol
LFTs
Serum thyroid peroxidase antibodies

Question 47

In primary care, if secondary hypothyroidism is suspected, what is the next management step?

Answer 47

Refer to specialis endocrinologist.

Question 48

When might you need to refer a patient with primary hypothyroidism to a specialist endocrinologist?

Answer 48

If the patient:

Has suspected subacute thyroiditis.
Has a goitre, nodule, or structural change in the thyroid gland.
Has suspected or associated endocrine disease such as Addison’s disease.
Is planning a pregnancy.
Has atypical or difficult to interpret thyroid function tests (TFTs).
Has a suspected underlying cause of hypothyroidism (such as medications).

Question 49

If specialist referral is not needed, how should primary hypothyroidism be treated?

Answer 49

With levothyroxine (LT4) monotherapy (should be taken in the morning on an empty stomach and before other medications).

**Advise that symptoms may lag behind treatment changes for several weeks or months.

Question 50

How should a patient who has been started on levothyroxine be monitored?

Answer 50

Review the person and recheck TSH levels every 3 months after initiation of LT4 therapy and adjust the dose according to symptoms and TFT results. Consider checking FT4 in addition if the person has ongoing symptoms on treatment.

Once the TSH level is stable (2 similar measurements within the reference range 3 months apart), check TSH annually.

Question 51

1) What is a sensible starting dose for levothyroxine in a healthy, young patient?
2) What is a sensible starting dose of levothyroxine in an elderly patient or a patient with IHD?
3) Why should you increase levothyroxine doses cautiously in elderly patients or in those with IHD?

Answer 51

1) 0-100mcg PO OD.
2) 25mcg PO OD and increase by 25mcg monthly until required dose is reached.
3) As levothyroxine can precipitate angina/ MI.

Question 52

1) What is a Myxoedema coma?
2) In who is a Myxoedema coma more likely to occur?
3) State 4 precipitants of a Myxoedema coma.
4) Give 4 possible presentations of Myxoedema coma.

Answer 52

1) The ultimate hypothyroid state before death.
2) Patients >65 years who may have had radio iodine treatment or thyroid/ pituitary surgery. Often, they have previously undiagnosed hypothyroidism or are poorly compliant with thyroid hormone medication.
3) Infection, stroke, MI, trauma.
4) Hypothermia, hyporeflexia, hypoglycaemia, bradycardia, coma, seizures, psychosis (which may precede a coma).

Question 53

1) Describe some features of a thyrotoxic crisis (storm).
2) Name 4 potential precipitants of a thyrotoxic crisis.
3) In whom could a thyrotoxic crisis occur in?
4) Why is the mortality rate of a thyrotoxic crisis high at 10%?

Answer 53

1) Temperature, confusion, agitation, coma, tachycardia, arrhythmias (AF), D+V, goitre, acute abdominal symptoms and CCF (all often symptoms systemic decompensation).
2) Precipitated by infection, MI, trauma, recent thyroid surgery or radio iodine treatment.
3) May occur in people with previously undiagnosed hyperthyroidism or those who have abruptly stopped antithyroid medication.
4) Due to hyperthermia, cardiac arrhythmias, multi-organ failure, and sepsis.