Thyroid function and dysfunction

Question 1

Where is the thyroid located?

Answer 1

The thyroid is a butterfly-shaped gland located at the base of the neck, just below the Adam’s apple

Question 2

What is a goitre and a nodule?

Answer 2

A goiter is an enlargement of the thyroid, the H-shaped gland that wraps around the front of your windpipe, just below your Adam’s apple. A goiter can be smooth and uniformly enlarged, called diffuse goiter, or it can be caused by one or more nodules within the gland, called nodular goiter.

Question 3

What is the cellular level arrangement of the thyroid?

Answer 3

• Thyroid is split into follicles filled with colloid- colloid is where the hormones are produced
• Lined with cuboidal thyroid epithelial cells
• In between cells are c cells which produce calcitonin

Question 4

What two main hormones are produced by the thyroid?

Answer 4

Triiodothyronine (T3) and Tetraiodothyronine (T4)

Question 5

How are thyroid hormones produced?

Answer 5

Iodine ions are trapped and moved into the colloid as iodine through the plasma membrane
Thyroid peroxidase and hydrogen peroxide catalyse the addition of iodine into a thyroglobulin protein skeleton
Tri= 3 iodine molecules, tetra= 4
-Enzymes breakdown the colloid and the hormone is then secreted out into the capillaries

Question 6

What is Tetraiodothyronine also known as?

Answer 6

Thyroxine

Question 7

Out of T3 and T4, which is the active hormone?

Answer 7

T3
T4 is the inactive form which can be converted to T3 quickly.

Question 8

What is T3 and T4 bound to in the circulation?

Answer 8

Proteins, most common is thyroxine binding globulin, but also transthyretin and albumin

Question 8

What percentage of T3 is produced directly from the thyroid gland?

Answer 8

20%
80% produced from peripheral conversion of T4 in liver, kidneys and muscle

Question 9

How is the thyroid stimulated?

Answer 9

Pituitary produces a hormone called thyroid stimulating hormones which docks to the TSH receptor in the thyroid

Question 10

What functions is the thyroid hormone involved in?

Answer 10

Growth development
Basal metabolic rate
Activating mental processes
Themogenesis in brown adipose tissuer

Question 11

What are the symptoms of an overactive thyroid?

Answer 11

Hot, rapid heart rate, sweaty, fast bowel movements, nervous, irritable

Question 12

What are the symptoms of an underactive thyroid?

Answer 12

Slow heart rate, cold, constipated, low moods and depression

Question 13

What are the main causes of hyperthyroidism?

Answer 13

Graves disease (75%)
Toxic multinodular goitre
Toxic nodule
Thyroiditis

Question 14

What is Graves disease?

Answer 14

An autoimmune disease where antibodies attack the thyroid to make it overactive
Can see a smoothly enlarged thyroid (goitre)
Can be associated with eye disease

Question 15

What is toxic multi nodular goitre?

Answer 15

Toxic nodular goiter involves an enlarged thyroid gland. The gland contains areas that have increased in size and formed nodules. One or more of these nodules produce too much thyroid hormone.

Question 16

Can you get signs of thyroid eye disease in toxic multi nodular goitre?

Answer 16

Can get eyelid lag or retention but no other features if thyroid eye disease

Question 17

Does the TSH decrease as there is more toxic nodules on the thyroid?

Answer 17

Decreases- thyroid is producing too much hormone so feedback loops stop production of TSH

Question 18

What is thyroiditis?

Answer 18

• Temporary overactivity of thyroid
• Can be triggered by pregnancy, infection or some drugs
• Sometimes followed by underactivity period

Question 19

What are the symptoms of hyperthyroidism?

Answer 19

• Weight loss despite good appetite (often very hungry)
• Tiredness
• Tremor
• Hot, sweaty
• Palpitations
• Diarrhoea
• Light/absent menses (stool)
• Mood: irritable, anxiety
• Eyes (change in appearance, red, gritty, painful, double vision)
• Muscle weakness

Question 20

On examination, what will you notice about patients with hyperthyroidism?

Answer 20

May have goitre or nodules, fast HR, agitated and talking fast, warm and sweaty, tremor and thyroid eye disease symptoms

Question 21

What are the eye symptoms related to graves disease?

Answer 21

• redness
• gritty sensation
• dry/watery eyes
• pain on eye movement
• swelling around etes
• propotsis (pushed forward appearance of eyes)
• double vision
• loss of colour vision

Question 22

What is the pathogenesis of thyroid eye disease?

Answer 22

• Problem initiates with beta cells producing TSH receptor antibodies, which bind to receptors in the thyroid and stimulate the production of T3 and T4
• T3 and T4 feedback and suppress TSH
• Antibodies will also dock with receptors in the recto-orbital tissue
• That causes adipocytes to produce fats and fibroblasts produce glycosaminoglycans which causes water retention and swelling

Question 23

How do you diagnose Graves disease?

Answer 23

Blood tests- check levels of T3/T4
Check TRAbs (TSH receptor antibodies)

Question 24

What is scintigraphy and how is it used to diagnose graves disease?

Answer 24

A procedure that produces pictures (scans) of structures inside the body, including areas where there are cancer cells Can produce imagine of thyroid if TRAbs are negative to diagnose.

Question 25

What happens if the thyroid gland does not show up on a scintigraphy scan?

Answer 25

May be thyroiditis- the gland has completely disappeared

Question 26

What happens if the thyroid gland does not show up on a scintigraphy scan?

Answer 26

May be thyroiditis- the gland has completely disappeared

Question 27

How can T3/T4 levels rise after thyroiditis?

Answer 27

Because gland has been damaged in infection (thyroiditis) and the pre-formed hormone has spilled out After acute period, T3/4 levels will drop

Question 28

What is the drug treatment for hyperthyroidism?

Answer 28

Antithyroid drugs such as carbimazole and propylthiouracil. It blocks the enzyme that catalyses the addiction of iodine to the protein sketeton

Question 29

What medication may be used to help with symptoms of tremor and increased HR?

Answer 29

Propanolol, good for tremor and increased HR (contradicted in asthma though)

Question 30

What are treatments for hyperthyroidism?

Answer 30

- Drugs - Radioactive iodine - Surgery

Question 31

What are the complications with using radioactive iodine?

Answer 31

I- 131 leads to risk of long term hypothyroidism Also have to restrict contact with children under 12 and pregnant women.

Question 32

What are the risks with surgery to treat hyperthyroidism?

Answer 32

Risk of long term hypothyroidism or damage to recurrent laryngeal nerve

Question 33

When is thyroid eye disease treated with steroids?

Answer 33

When the disease is active (redness, swelling, pain, change in visual function) When the disease is inactive there may be severe damage left behind but does respond to steroids

Question 34

What are treatment options for thyroid eye disease?

Answer 34

Steroids Selenium 200mcg daily Topical lubricants Smoking cessation If there do not work, additional immunosuppressant treatment and orbital radiotherapy

Question 35

What are the symptoms of hypothyroidism?

Answer 35

- Tired - Weight gain, puffy eyes and skin - Feeling cold - Slow heart rate - Constipation - Dry hair and skin - Heavy periods (menorrhagia) - Hyperlipidaemia

Question 36

If a patient has normal thyroid function tests but the symptoms of hypothyroidism, should they be given thyroxin?

Answer 36

There is no evidence for it

Question 37

What are the common causes of hypothyroidism?

Answer 37

Hashimoto's thyroititis Iatrogenic Spontaneous atrophy of thyroid Temporary thyroiditis e.g. viral or postpartum

Question 38

What is Hashimoto's thyroiditis?

Answer 38

Antibodies attack thyroid and make it underactive It is permanent and runs in families

Question 39

Why is iodine deficiency not a issue in the UK for hypothyroidism?

Answer 39

There is a iodine level screening test for babies in the UK

Question 40

What is the manufactured version of thyroid hormone?

Answer 40

Levothyroxine

Question 41

What are the tests for diagnosis of hypothyroidism?

Answer 41

If T4 is low and TSH is high, no further tests needed

Question 42

What is the half life of levothyroxine?

Answer 42

7 days

Question 43

When is levothyroxine best taken?

Answer 43

In the morning on an empty stomach

Question 44

What medications can impair levothyroxine absorption?

Answer 44

Omeprazole and lansoprazole (proton pump inhibitors) H2 antagonists (ranitidine) Iron, calcium, aluminium (OTC medication)

Question 45

What medications require an increased levothyroxine requirement?

Answer 45

Oestroegen or anticonvulsants

Question 46

What is the first sign of hypothyroidism or sub-clinical hypothyroidism?

Answer 46

TSH is more sensitive than T4, so even if T4 levels are still within reference range, TSH will rise up outwit the normal range

Question 47

What is the main cause of subclinical hypothyroidism?

Answer 47

Autoimmune chronic thyroiditis

Question 48

What were the risk factors found for women for hypothyroidism in the Wickham study?

Answer 48

Raised TSH Positive peroxidase antibodies Both= much greater chance

Question 49

What are the symptoms of primary, subclinical and secondary hypothyroidism?

Answer 49

Question 50

What indicates non-thyroidal illness that is having an effect on the thyroid?

Answer 50

Low T3

Question 51

Why can some non-thyroidal illness cause a rise in free T4 in early stage of illness?

Answer 51

Illness can effect thyroid hormone binding proteins which reduces total hormone but initially raises free hormone

Question 52

Why does free T3 fall in non thyroidal illness?

Answer 52

There is an impaired T4 hepatic uptake and conversion to T3 during illness

Question 53

What controls TSH release and how can it be suppressed?

Answer 53

Thyrotropin releasing hormone controls TSH release- it can be suppressed by cytosines and glucocorticoids (e.g. cortisol and stress hormone)

Question 54

What causes suppression of TSH?

Answer 54

Dopamine Suppressed TRH Modified carbohydrate residues

Question 55

Should thyroid function tests be performed on patients with chronic or acute illness?

Answer 55

No, unless thyroid disease is considered to be the cause of their presenting complaint

Question 56

What test results will non-thyroidal illness produce?

Answer 56

Elevated free T4 levels, and suppressed TSH (similar to primary hyperthyroidism) but with low T3

Question 57

When does the foetus require T4?

Answer 57

- The foetus needs thyroxin from about 4th or 5th week- important for CNS and development of foetus - Foetus uses maternal T4 exclusively up to 10 weeks and partially thereafter.

Question 58

What is untreated hypothyroidism associated with in pregnant women?

Answer 58

Infertility, miscarriage Pre-eclampsia, Premature delivery Increased foetal mortality, impaired neurological development

Question 59

What is subclinical hypotension (untreated) associated with in pregnant women?

Answer 59

Neurodevelopmental delays, placental abruption

Question 60

What happens when a hypothyroid women becomes pregnant?

Answer 60

The thyroxine dose needs to increase straight away

Question 61

Why at the start of pregnancy can TSH levels drop and T3/4 levels rise?

Answer 61

- Early stage of pregnancy, HCG rises (hormone in pregnancy). HCG is structurally similar to TSH and mimics some functions of TSH. - This is why there is low TSH levels- is suppressed and high FT4 and FT3 levels - This is temporary and no thyroid drugs are needed.

Question 62

What is HCG?

Answer 62

Human chorionic gonadotropin

Question 63

Why do you only check free hormone levels of T3/4 in pregnancy?

Answer 63

In pregnancy, only check free hormone, not bound hormone as oestrogen can increase the number of proteins that the hormones can bind to

Question 64

Why is it important to measure TRAb's in pregnancy patients with Graves disease?

Answer 64

TRAbs can cross placenta and act on the fetal thyroid gland by 20 weeks to cause neonatal hyperthyroidism

Question 65

Why is a thyroid uptake scan not necessary for all patients to make a diagnosis of hyperthyroidism?

Answer 65

If TRABs are positive scan is not needed?

Question 66

What is the 131I-uptake test and scan used for?

Answer 66

Used to see what areas of the scan are producing iodine- different patterns for different causes of hyperthyroidism

Question 67

How does carbimazole exert its antithyroid activity?

Answer 67

Inhibits T4/3 synthesis by inhibiting thyroid peroxidase