Thyroid conditions (Hypo and Hyperthyroidism)

Question 1

What is the most likely cause of hyperthyroidism?

Answer 1

Graves disease

Question 2

What is some background information of Graves disease? (age at diagnosis, prevalence, m : f ratio)

Answer 2

Normally patients are diagnosed between the ages of 30-60 years
Females are 10x more likely to have Graves disease than men and the prevalence is
20 in 1000 females and 2 in 1000 men

Question 3

What type of condition is Graves disease?

Answer 3

It is an autoimmune condition where thyroid stimulating antibodies are produced which closely mimics thyroid stimulating hormone which acts on the thyroid stimulating receptor in the thyroid gland, over stimulating it.

Question 4

What are some of the clinical presentations of Graves disease?

Answer 4

It increases the metabolic rate and therefore Leads to weight loss
Increased appetite
Palpitations
Sweating
Tremor
Anxiety
Diarrhea
Can’t tolerate heat
Tachycardia
Fatigue
Sexual dysfunction

Question 5

What are the most distinguishable features of Graves Disease?

Answer 5

Exopthalamus (bulging of the eye) which causes further eye complications such as swelling of the eyelids and double vision.
Diffuse goitre with no nodules
Pretibal myxoedema

Question 6

Which diagnostic tests are used to confirm Graves disease?

Answer 6

Blood tests
Radioactive iodine uptake
Thyroid scan
Doppler blood flow measurement

Question 7

How are blood tests used to confirm Graves disease?

Answer 7

Can detect thyroid stimulating antibodies or immunoglobulin, and you would expect low TSH and high free T4 and T3 (above the reference range).

Question 8

What is the normal reference range for T3, T4 and TSH?

Answer 8

T3: (4 - 7.8 pmol/L)
T4: (10 - 24 pmol/L)
TSH: (0.4 - 4.5 microunits/mL)

Question 9

Describe some of the other possible causes of hyperthyroidism?

Answer 9

Toxic nodular goitre
Thyroid adenomas

Question 10

What is toxic nodular goitre?

Answer 10

It is the enlargement of the thyroid gland in which contains small round masses or nodules throughout. The enlarged thyroid gland over-secretes the thyroid hormone (T4 and T3) and these nodules act independently from the normal feedback cycle.

Question 11

What are thyroid adenomas?

Answer 11

Overgrowth of the thyroid tissue (benign tissue) that also over secretes the thyroid hormone.

Question 12

What is toxic nodular goitre also known as?

Answer 12

Plummer’s disease

Question 13

What results would you expect of TSH levels, T4 and T3 levels following a routine blood test if there was suspicion of hyperthyroidism?

Answer 13

You would expect:

High T4 and T3 levels (above 10-24 pmol/L and 4-7.8 pmol/L)

Low TSH levels (below 0.4-4.5 uIU/mL)/

Question 14

Explain the clinical results of TSH, T4 and T3 levels in hyperthyroidism?

Answer 14

In all three clinical examples there has been hyper-secretion of the thyroid hormones (either due to thyroid stimulating antibodies or benign tumours or nodules on the thyroid gland) contributing to high levels of T4 and T3 which then induces a negative feedback cycle resulting in low levels of TSH.

Question 15

Explain the difference in pathology between primary and secondary hyperthyroidism.

Answer 15

Primary hyperthyroidism is when there is a defect in the thyroid gland itself which causes the over-production of the thyroid hormones (T4 and T3).
Secondary hyperthyroidism is when there is a defect in the hypothylamus or anterior pituitary gland which over secretes thyroid stimulating hormone which then contributes to the high thyroid output.

Question 16

What is pretibal myxoedmea and when does it occur?

Answer 16

It is a dermological condition caused by deposition of mucin under the skin contributing to a waxy appearance.
The condition is specific to Graves disease and is caused by a reaction of the tissue under the skin with TSH receptor antibodies.

Question 17

Which demographic would you more likely expect to see with toxic multinodular goitre?

Answer 17

Over 50s

Question 18

What is the first line treatment of benign thyroid adenomas?

Answer 18

Depending how many adenomas are present but most likely surgery

Question 19

What are some of the clinical presentations of De Quervain’s thyroiditis?

Answer 19

Painful swelling of the thyroid gland
High temperature
Pain in the neck, jaw or ear

Question 20

How would you expect the TSH, T4, T3 levels to change with a patient with De Quervain’s thyroiditis?

Answer 20

The first phase is known as the hyperthyroid phase therefore you would expect high levels of T4 and T3 but low levels of TSH.

The second phase is the hypothyroid phase caused by the negative feedback following the hyperthyroid phase so you would expect low levels of T4 and T3 but high levels most likely of TSH.

Question 21

How long does each phase of De Quervain’s thyroiditis last?

Answer 21

Hyperthyroidism phase (and the symptoms associated with it) lasts a couple of days whereas hypothyroidism (and symptoms) phase can last weeks to months.

Question 22

What treatment is usually prescribed for De Quervain’s thyroiditis?

Answer 22

NSAIDS for symptomatic relief and possibly beta blockers to help with symptoms associated with hyperthyroidism (palpitations, anxiety, tremor)

Question 23

What are some of the clinical presentations of thyrotoxic crisis?

Answer 23

Pyrexia
Tachycardia
Delerium

Question 24

Which demographic would be most likely to experience De Quervain’s thyroiditis?

Answer 24

Women aged 20-50 years

Question 25

What causes a thyrotoxic crisis to occur?

Answer 25

Normally due to underlying Graves' disease or toxic multinodular goitre where there is a sudden onset of hyperthyroidism.

Question 26

What are some of the clinical presentations of a thyrotoxic crisis?

Answer 26

Hyperpyrexia (over 41 degrees) Heart rate over 140bpm (with or without other arrhythmias or atrial fibrillation) Nausea Vomitting Diarrhoea Abdominal pain Confusion Delirium Seizures Coma

Question 27

When does thyroid storm most likely occur?

Answer 27

In a patient with underlying thyroid conditions in addition to intercurrent illness, trauma or emergency surgery

Question 28

What does the management of thyroid storm involve?

Answer 28

Fluid resuscitation Anti-arrhythmias B-blockers (5mg IV propanolol)

Question 29

What is the first line treatment for hyperthyroidism in Graves disease?

Answer 29

Anti-thyroid drugs: more specifically Carbimazole

Question 30

When is normal thyroid levels achieved with Carbimazole?

Answer 30

After 4-12 weeks and then a maintenance dose is introduced.

Question 31

What are the two options regarding when deciding a maintenance dose of Carbimazole?

Answer 31

Either titrated to maintain normal levels (Titration block) or Titrated in which all the thyroid hormone is blocked and then replaced with Levothyroxine and is adjusted according to symptoms (block and replace).

Question 32

How often would you monitor a patient on anti-thyroid medication?

Answer 32

Every 6 weeks until their thyroid hormone levels are within the normal range and then every 3 months.

Question 33

When does a patient with hyperthyroidism reach remission?

Answer 33

Normally 12 to 18 months of Carbimazole treatment

Question 34

What is a serious side effect of the second line treatment of hyperthyroidism?

Answer 34

Propyluracil can cause severe hepatic impairment and potentially death

Question 35

Explain the principle of radioactive iodine therapy?

Answer 35

It is taken orally by the patient and the localised radioactive iodine releases radiation which destroys a portion of the thyroid gland and thyroid secreting cells resulting in a reduced secretion of thyroid hormones.

Question 36

What is a disadvantage of radioactive iodine therapy?

Answer 36

Remission takes six months Can overshoot and result in hypothyroidism requiring the needs of levothyroxine Can't be pregnant or get pregnant for six months Can't be around young children or pregnant women for 3 weeks Limit contact with anybody for up to 3 days afterwards

Question 37

Explain the purpose of Beta blocker therapy in those with hyperthyroidism?

Answer 37

Blocks the adrenaline produced side effects such as tachycardia, tremor, anxiety and sweating.

Question 38

Which beta blocker is usually prescribed in the treatment of hyperthyroidism and why?

Answer 38

Propanolol as it is a non-selective beta blocker and will act on the beta-1, beta-2 and low affinity for beta-3 and therefore reduce symptoms such as tremor, tachycardia etc. However an additional benefit of propanolol is that it inhibit the peripheral conversion of T4 to the more biologically active hormone, T3.

Question 39

In which other clinical conditions would propanolol be contra-indicated?

Answer 39

Use with caution in patients who also have diabetes especially those who experience hypoglycaemia (propranolol blocks the adrenegically mediated symptoms of a hypo). Also those with asthma who are taking Beta-2 agonists.

Question 40

What would be a suitable alternative when propranolol is contra-indicated in hyperthyroidism?

Answer 40

Diltiazem

Question 41

What is a disadvantage of surgery for treating hyperthyroidism?

Answer 41

Patient will require levothyroxine for life Hyperthyroidism can reoccur or hypoparathyroidism.

Question 42

What is the mechanism of Carbimazole and Propylthiouracil?

Answer 42

They inhibit thyroperoxidase which hence prevents the iodination of thyrosines and hence preventing synthesis of the thyroid hormone.

Question 43

What is an additional mechanism of Propylthiouracil?

Answer 43

Inhibits T4 to T3 conversion

Question 44

What are some of the side effects of thioureylenes?

Answer 44

Rashes (in 5% of patients) Agranulocytosis (in 3% of patients)

Question 45

What is a crucial counselling point if a patient is on Carbimazole or Propylthiouracil (thioureylenes)?

Answer 45

Patients need to report to their GP if they experience any of the following side effects due to risk of agranulocytosis: Sore throat Mouth ulcers Fever Malaise Bruising or bleeding Patient also needs to be aware of how to recognize signs of liver disorder such as: Persistent nausea, vomitting Malaise Jaundice They should discontinue medication immediately and report to their GP.

Question 46

What happens in agranulocytosis?

Answer 46

Depletes neutrophils leading to increased susceptibility of bacterial infections Depletes red blood cells leading to increased risk of bleeding

Question 47

When does the maximum effect of radiotherapy iodine occur?

Answer 47

After 4 months of treatment

Question 48

When is high doses of iodine given?

Answer 48

When preparing for surgery or during a thyroid storm

Question 49

When is the effect of Lugol's iodine felt the most?

Answer 49

Symptoms subside after 1-2 days and then the maximum effect is felt 10-15 days and then effect decreases

Question 50

Which drug can induce thyroid dysfunction?

Answer 50

Amiodarone (used for cardiac arrthymias) can induce either hypo or hyperthyroidism

Question 51

Which monitoring parameters would you assess before prescribing amiodarone?

Answer 51

Baseline TFTs before prescribing and then at every six months of taking the medication.

Question 52

When are people most likely to be diagnosed with hypothyroidism?

Answer 52

Between the age of 30-60 years and women are 10x more likely to have hypothyroidism than men.

Question 53

What is the most common causes of hypothyroidism in the developed world?

Answer 53

Hashimoto's thyroiditis

Question 54

What is Hashimoto's thyroiditis?

Answer 54

It is an auto-immune disease in which the body produces anti thyroid perioxidase antibodies or anti thyroglobulin antibodies against thyroglobulin (essential for the synthesis of T4 and T3.

Question 55

Aside from Hashimoto's thyroiditis what are the other causes of primary hypothyroidism?

Answer 55

Due to lack of dietary iodine, quite common in the developing world or drug induced (amiodarone)

Question 56

What are some of the clinical presentations of Hashimoto's thyroiditis and hypothyrodism in general?

Answer 56

Mainly goitre and then when hypothyroidism sets in, there are many clinical presentations such as: Tiredness Muscle weakness Slow speech Dry skin Constipation Bradycardia Cold intolerance Depression Weight gain Sparse thin hair Fluid retention Amenerrhoea

Question 57

What is the main symptom of hypothyroidism in children?

Answer 57

Growth failure

Question 58

Describe the difference between primary, secondary and tertiary hypothyroidism?

Answer 58

Primary hypothyroidism occurs when there is a defect with the thyroid gland and hence insufficient thyroid hormone is secreted (e.g Hashimoto's syndrome in children) Secondary hypothyroidism is caused due to a defect with the anterior pituitary which means it can no longer produce sufficient levels of TSH (due to a pituitary tumour). Tertiary hypothyroidism is caused by a defect with the hypothylamus and secretes low levels of TRH/

Question 59

Geographically, in the world where is hypothyroidism due to iodine deficiency most likely to occur?

Answer 59

Hypothyroidism due to iodine deficiency is most likely to occur in developing countries inland with no access to the sea. In these countries there would be little incorporation of fish into their diet, which is one of the richest sources of iodine (specifically shellfish). Closer to the sea there is also richer iodine in soil.

Question 60

Apart from shellfish which other foods have high levels of iodine?

Answer 60

Dairy Eggs Some fruits such as strawberries, cranberries and pineapple Fish in general (seaweed)

Question 61

When does congenital myxoedema occur?

Answer 61

During pre-natal development

Question 62

What is congenital myxoedema and what are some of the clinical presentations in infancy?

Answer 62

A severe thyroid condition which occurs in infancy and some of the clinical presentations include difficulties feeding, sleeping, constipation and jaundice.

Question 63

Are babies tested for hypothyroidism?

Answer 63

Yes in the UK all babies are tested soon after birth by taking blood from a heel prick test. If there is a suspicion of hypothyroidism, then additional tests will be conducted such as a scan of the neck to confirm the presence of the thyroid gland.

Question 64

What are some of the clinical presentations of severe congenital hypothyroidism in childhood?

Answer 64

Growth failure Intellectual disability Dystrophy of the bones Low basal metabolism

Question 65

What is myxoedema coma and when does it occur?

Answer 65

It is a rare, life-threatening condition due to severe, untreated hypothyroidism. It is when the mechanisms the body has adapted to using to compensate for low T4 and T3 levels fail to maintain homeostasis and become overwhelmed by hypothermia, infection or other precipitating factors.

Question 66

What are some of the clinical presentations of myxoedema coma?

Answer 66

Usually begin to present with some of the usual symptoms of hypothyroidism (dry skin, weight gain, thin sparse hair etc). May have cognitive decline (memory loss, confusion, low mood). They have a core body temperature of below 35.5 degrees Normally hypotensive and bradycardic Hypoxia and Hypercapnia

Question 67

What would you expect the lab results to be in a patient with hypothyroidism?

Answer 67

You would expect: Low T4 and T3 levels (below 10-24 pmol/L and 4-7.8 pmol/L) High TSH levels (above 0.4-4.5 uIU/mL)/

Question 68

Explain the TSH, T4 and T3 levels in a patient with hypothyroidism?

Answer 68

As insufficient T4 and T3 levels are produced from the thyroid gland so there is no negative feedback loop acting on the anterior pituitary so it continues to produce high concentrations of TSH to try and stimulate the thyroid gland.

Question 69

Which treatments for hyperthyroidism can induce hypothyroidism?

Answer 69

Carbimazole Prophylthiouracil Radioactive iodine Thyroid surgery

Question 70

What is hypopituitism?

Answer 70

When the pituitary gland fails to secrete TSH and therefore insufficient levels fail to stimulate sufficient T4 and T3 from the thyroid gland.

Question 71

What are some of the causes of hypopituitism?

Answer 71

Pituitary adenomas Infections Vascular (Sheehan's syndrome, significant blood loss following childbirth) Radiation

Question 72

How do levels of TSH, T4 and T3 differ for secondary hypothyroidism and why?

Answer 72

You would expect: Low T4 and T3 levels (below 10-24 pmol/L and 4-7.8 pmol/L) Low TSH levels (below 0.4-4.5 uIU/mL) As the anterior pituitary is failing to produce sufficient TSH, there is lack of stimulation on the thyroid gland and hence low levels of T4 and T3 are produced.

Question 73

What is the first line treatment and starting dose for hypothyroidism?

Answer 73

Oral Levothyroxine Starting dose: 50-100mcg to be taken in the morning on an empty stomach 25mcg for elderly

Question 74

How does levothyroxine work?

Answer 74

It is synthetic T4 which is metabolised to T3 (more biologically active) in the liver and kidney. T3 stimulates protein synthesis and energy metabolism

Question 75

How regularly do you monitor TSH levels for a patient taking oral levothyroxine?

Answer 75

It can take up to 6 months for TSH levels to remain in the reference range and therefore you would usually measure TSH levels every 2-3 months after beginning.

Question 76

How would you titrate the dose of levothyroxine according to TSH levels?

Answer 76

If the TSH levels are too high, the dose of levothyroxine is too low and therefore increase the dose by 25-50 mcg. If the TSH levels are too low, the dose is too high and therefore reduce the dose by 25-50mcg.

Question 77

What is the usual maintenance dose of levothyroxine?

Answer 77

100-150 mcg

Question 78

When is Liothyronine used and why?

Answer 78

It is used during a hypothyroid crisis as it is synthetic T3 and is therefore more rapidly acting than levothyroxine as it does not have to be metabolised first.

Question 79

What additional testing is required for Liothyronine?

Answer 79

Blood levels of TFTS to ensure hyperthyroidism does not occur.

Question 80

Aside from Levothyroxine and Liothyronine what additional drug can be used in the treatment of hypothyroidism?

Answer 80

Iodine, specifically used in iodine deficiency.

Question 81

Describe the anatomy of the thyroid gland.

Answer 81

It is a small butterfly shaped gland in the neck in front of the larynx (voice box) and is highly vascular, transporting synthesised hormones to their target organs and glands.

Question 82

What are the two hormones produced by the thyroid gland?

Answer 82

Thyroid hormone- thyroxine (T4) and tri-iodothyronine (T3) Calcitonin- regulates calcium metabolism

Question 83

What are some of the functions of T4 and T3?

Answer 83

T4 is metabolised into the more biologically potent T3, which has many functions including when it is produced: It increases the basal metabolic rate Increases heat production Influences synthesis and degradation of major fuels in the body Increases response to catecholamines Stimulates growth hormone and IGF-1 secretion Activity of the CNS

Question 84

What is the structural and functional unit of the thyroid gland?

Answer 84

Thyroid follicles which are comprised of follicular (epithelial cells).

Question 85

Describe the thyroid hormone release cycle starting from the hypothalamus.

Answer 85

In the hypothalamus the paraventricular nucleus (neurons) secretes thryrotropin releasing hormone (TRH). The TRH then stimulates tyrotropes in the anterior pituitary, which then pump out thyroid stimulating hormone (TSH). TSH then circulates in the blood and acts on the receptor on the outside of thyroid cell. The G stimulatory protein becomes bound to GDP and then binds to adenylyl cyclase, triggering the cAMP signalling pathway. Protein kinase A phosphorylates a transcription factor which then promotes genes for hormone synthesis.

Question 86

How is T4 converted to T3?

Answer 86

Both T4 and T3 are synthesised by iodination of tyrosine. T4 contains four iodines whereas T3 only has three. Therefore T4 is converted to T3 by de-iodinases in tissues.

Question 87

What is the thyroid hormone transporter and why is it required?

Answer 87

Thyroxine binding globulin and it is required due to the hydrophobic nature of the hormone.

Question 88

What two proteins does thyroid hormone bind to?

Answer 88

Albumin and transthyretin

Question 89

What is the function of thyroglobulin in the synthesis of the thyroid hormone?

Answer 89

Thyroglobulin is produced as a downstream product of the cAMP. Thyroglobulin contains tyrosine amino acids in its peptide chain. Iodine then attaches to the tyrosine residue of the thyroglobulin.

Question 90

How is iodide converted to iodine?

Answer 90

Oxidised into the iodine by thyroid peroxidase.

Question 91

How are iodide ions transported into the follicular cells?

Answer 91

There are low concentrations of iodide ions in the blood but high concentrations within the cell. Therefore iodide has to be transported against its concentration gradient by a Na+I- co-transporter. Sodium moves down its concentration gradient into the cell and brings iodide with it. It is an example of secondary active transport.

Question 92

How is T4 synthesised?

Answer 92

By fusion of two di-iodotyrosine molecules (overall four iodine molecules)

Question 93

How is T3 synthesised?

Answer 93

By fusion of one mono-iodotyrosine and one di-iodotyrosine (overall three iodine molecules).

Question 94

How do plasma iodine levels control the synthesis of thyroid hormone?

Answer 94

Increase in iodine uptake, increases T3 and T4 synthesis and decreases thyroid stimulating hormone. Decrease in iodine uptake, decreases T3 and T4 synthesis and increases thyroid stimulating hormone.

Question 95

What are the four T3 receptors?

Answer 95

Alpha 1 Alpha 2 Beta 1 Beta 2

Question 96

When one of the T3 receptors are activated what are some of the downstream signalling effects?

Answer 96

Alters stimulation in genes responsible for the control of metabolic activity. This results in an increase in: O2 consumption Body temperature Cardiac output Breakdown of energy stores

Question 97

Aside from thyroid hormones what other hormones affect metabolism?

Answer 97

Insulin and Catecholamines

Question 98

What are the average ages of developing thyroid cancer?

Answer 98

More prevalent in women than men and occurs at a younger age in women (35-39) whereas men the average age is 70.

Question 99

What is the survival rate of thyroid cancer?

Answer 99

85%

Question 100

What is the most common type of thyroid cancer?

Answer 100

Papillary thyroid cancer (90% of all cases).

Question 101

Where can papillary and follicular thyroid cancer spread to?

Answer 101

Papillary cancer can spread to the lymph nodes in the neck or surrounding tissue. Follicular thyroid cancer can spread to the lungs or bones.

Question 102

How does the demographic diagnosed with thyroid cancer differ between papillary and follicular and Hurthle cell thyroid cancer?

Answer 102

Papillary tends to be younger whereas follicular occurs in middle aged and Hurthle cell tends to be older women.

Question 103

Are Hürthle cell tumours benign or malignant ?

Answer 103

They can be either

Question 104

What is the most serious type of thyroid cancer?

Answer 104

Anaplastic thyroid cancer which is a very aggressive form of cancer and is highly likely to metasises. Tends to be diagnosed in older women.

Question 105

Describe medullary thyroid cancer.

Answer 105

It is a rare type of thyroid cancer originating from C-cells and about 25% of cases are inherited by a faulty gene.

Question 106

What are some risk factors of thyroid cancer?

Answer 106

Females are more likely than males Exposure to high levels of radiation Benign thyroid disease Being overweight First generation relative Inherited faulty genes

Question 107

What was given to citizens in nearby countries following the Chernobyl disaster?

Answer 107

They given potassium iodide tablets which floods the thyroid with iodine and prevents the radioactive iodine from being absorbed (6-12 hrs before exposure).

Question 108

What are some of the main symptoms of thyroid cancer?

Answer 108

Lump in the neck Hoarse voice Sore throat Difficulty swallowing

Question 109

What treatment is usually given for thyroid cancer?

Answer 109

Surgery Radioactive iodine Chemotherapy Targeted chemotherapy (when above options have not worked)

Question 110

Which chemotherapeutic are usually given for thyroid cancer?

Answer 110

Doxorubicin or Cisplatin

Question 111

What do targeted chemotherapies for thyroid cancer target?

Answer 111

The vascular endothelial growth factor receptor pathway and other growth factor pathways as the thyroid is vascular rich

Question 112

Give some examples of targeted chemotherapies and their therapeutic targets?

Answer 112

Vandetanib – inhibits VEGFR2 and EGFR and is used in the treatment of medullary thyroid cancer Cabozantinib – inhibts c-Met and VEGFR2, also used in the treatment of medullary thyroid cancer Lenvatinib – inhibits VEGFR and FGFR used to treat papillary and follicular thyroid cancer