Thyroid

Question 1

Where is the thyroid found and what does it look like (four parts)?

Answer 1

The thyroid gland has two lobes (left and right). Found in the neck. In front of the trachea. Isthmus joins the two lobes. Pyramidal lobe above the isthmus and present in only some.

Question 2

What two nerves go just past the thyroid gland?

Answer 2

Recurrent Laryngeal Nerve – damages voice forever (complication of thyroidectomy). Vagus nerve.

Question 3

What is the embryology of the thyroid?

Answer 3

Originates from the BACK of the tongue. Outpouching (outward growth and movement) forms a duct which elongates down. This migrates down the neck and divides into two lobes. It’s at its final position by week 7 of embryonic development. The duct disappears. The thyroid gland THEN develops.

Question 4

What is the outpouching duct called?

Answer 4

Called the thyroglossal duct.

Question 5

What does the thyroglossal duct leave behind on the tongue?

Answer 5

Foramen caecum at back of tongue.

Question 6

Why – based on embryology – do only some people have a pyramidal lobe?

Answer 6

It’s left behind from the downward migration of thyroid development.

Question 7

How heavy is the thyroid gland?

Answer 7

20g.

Question 8

What are the dimensions of EACH thyroid lobe?

Answer 8

4 x 2.5 x 2.5 cm. Right lobe is larger.

Question 9

How would you describe the histology of the thyroid?

Answer 9

Tissue contains follicles which contains follicular cells. In the middle is a colloid (which is spherical). Around the follicles, there are parafollicular cells.

Question 10

What hormones are secreted by the hormone? (x2)

Answer 10

T3 and T4.

Question 11

What does a follicular cell look like?

Answer 11

Apical membrane in contact with colloid. Basolateral membrane in contact with blood vessel. TSH receptor found on basolateral membrane (TSH from the anterior pituitary, binds here).

Question 12

How does TSH stimulate the thyroid gland? (x4)

Answer 12

1. Uptake of iodide (I-): taken from the blood into the cells. Through sodium-iodide symporters which pumps two Na+ and one I- into the cell. Iodide then transported into the colloid across the apical membrane. This is important because thyroid hormones require iodide. 2. Stimulates thyroglobulin synthesis: a protein synthesised in the follicular cells and also goes into the colloid. 3. Stimulates production of TPO enzyme – works in presence of H2O2 for iodination of Thyroglobulin, and coupling reactions. 4. Stimulates actions of lysosome in thyroid hormone production.

Question 13

What is the process of thyroid hormone synthesis?

Answer 13

Iodine is pumped into colloid by pendrin pumps.

Thyroglobulin is iodinated with the iodide in the colloid. The iodine is added onto tyrosine amino acids (or tyrosyl residues) in the thyroglobulin protein. Catalysed by thyroperoxidase (TPO).

Products are monoiodotyrosine (MIT) (if one iodide is added at one position) AND diiodotyrosine (DIT) (if two iodides are added at two positions).

Coupling reactions create hormones out of the MIT and DIT intermediates.

• Thyroxine is produced by combining two DITs.
• Triiodothyronine is produced by combining one molecule of MIT and one molecule of DIT.

Iodination and coupling occurs on the apical membrane.

Hormones then taken up back into the follicular cells and into the cells. They are processed by lysosomes in the follicular cells. Each are cleaved to form T4 and T3 respectively which are released into the blood.

NB: the colloid stores thyroxine so it can be released immediately when needed.

Question 14

Where is thyroglobulin made?

Answer 14

Thyroid gland only.

Question 15

What is another name for thyroid hormones?

Answer 15

Iodothyronines because of how they are synthesised.

Question 16

How are thyroid hormones transported in the blood? (x4)

Answer 16

Transported bound to proteins. Mostly to thyroxine-binding globulin (TBG), though some also transported on albumin and prealbumin (OR transthyretin). Very small amount of T3 and T4 are unbound – these are the bioactive components.

NB: TBG is NOT thyroglobulin. Don’t confuse them because they sound similar. Thyroglobulin is what’s used to make thyroid hormones. TBG binds those hormones.

Question 17

What hormone is mainly secreted by the thyroid gland? Which of the two is inactive and active?

Answer 17

T4 is the main hormone secreted by the thyroid gland. T3 is the active hormone. T4 is the inactive hormone.

Question 18

How is T4 activated? Two products of the process?

Answer 18

Occurs in the peripheral tissues.

Through deiodination – removing ONE iodide.

T4 can be deiodinated into:

□ T3 (active thyroid hormone).

□ OR, REVERSE T3 (inactive form), where iodide is removed from a different position on the protein. (i.e. deiodination produces active form if the same iodide is removed every time).

Question 19

What are the three mechanisms of action of T3? (x3) Which is most prominent?

Answer 19

T3 binds to Thyroid Hormone Receptor which stimulates transcription of a number of genes = protein synthesis. THIS IS ITS MOST PROMINENT EFFECT. Binds to mitochondria to stimulate metabolic activity. Binds to ion channels on cell surface membrane.

Question 20

What do thyroid hormones effect? (x7)

Answer 20

Affects fetal growth and development – mainly potentiates brain development.

Increases basal metabolic rate – increases protein, fat and carbohydrate catabolism/metabolism.

Potentiates the actions of catecholamines – increases heart rate and lipolysis. BASAL METABOLIC RATE IS KEY – this is the causation of many of the symptoms in thyroid-related diseases.

Effects GI tract.

Effects CNS.

Effects reproductive system – e.g. thickens endometrium in females.

Effects respiratory system – increases ventilation rate.

Question 21

What is the latent period of the thyroid hormones?

Answer 21

Time between secretion and response. T3 = 12h; T4 = 72h.

Question 22

What are the half-lives of the thyroid hormones?

Answer 22

T3 = 2 days; T4 = 8 days.

Question 23

How is thyroid hormone production stimulated/inhibited? (x2 and x3)

Answer 23

Thyroid hormone production is controlled by TSH from the anterior pituitary.

STIMULATES: TSH secretion in the pituitary is stimulated by TRH (Thyrotropin-releasing hormone) in the hypothalamus. TRH stimulates thyrotroph cells to produce TSH. Oestrogens stimulate TSH release.

INHIBITS: T3/T4 inhibits TSH secretion (directly on adenopophysis or indirectly on hypothalamus). Influx of iodide inhibits thyroid hormone release – called the Wolff-Chaikoff effect. Glucocorticoids inhibit TSH release.

[This is in addition to agents that stimulate and inhibit hypothalamus and adenopophysis that are covered in the Pituitary Gland notes.]

Question 24

What is alternative name for TSH?

Answer 24

Thyrotrophin!!! REALLY REMEMBER THIS!!! MARK AS RED.

Question 25

What does the Hypothalamus-Pituitary-Thyroid axis look like?

Answer 25

Very simple.

Question 26

What happens when hypothyroidism occurs at birth?

Answer 26

Cretinism (stunted mental and physical growth).

Question 27

What are the symptoms of cretinism? (x4)

Answer 27

Brain damage. Short stature. Results in subfertility (refers to an individual who is not infertile, but also not optimally primed to conceive). Irregular periods.

Question 28

Why does hypothyroidism not affect a baby in utero?

Answer 28

Because thyroxine from the mother crosses the placenta. Hence, hypothyroidism affects neonates (i.e. from birth).

Question 29

Why are thyroid diseases more common in women? (x2)

Answer 29

Some of the most common thyroid diseases are autoimmune (Graves’ disease). Pregnancy predisposes autoimmune diseases. Menstruation and oestrogen surges also predispose thyroid diseases.

Question 30

What is primary hypothyroidism also known as?

Answer 30

Myxoedema.

Question 31

What’s the distinction between primary and secondary hypothyroidism?

Answer 31

Primary = Failure of the thyroid to produce thyroid hormone. Secondary = caused externally from the thyroid. Underproduction of TSH by the pituitary. Secondary hypothyroidism is very uncommon compared to primary.

Question 32

What are the causes of primary hypothyroidism? (x2)

Answer 32

Autoimmune damage. Operation – thyroid removal.

Question 33

What happens in relation to the HPT axis with primary hypothyroidism? (x3) Clinical application?

Answer 33

Thyroxine levels drop. T3 and T4 negatively feedback on the hypothalamus and pituitary. However, now that there’s decreased levels of T3 and T4 (thyroxine); TRH and TSH levels increase to try and rectify T3 and T4 levels. This is why babies with cretinism have high TSH levels. Doctors therefore administer thyroxine when this occurs – to increase thyroxine levels AND reduce TSH levels.

Question 34

What are the features of primary hypothyroidism? (x8) (x1 main point)

Answer 34

ALL SYMPTOMS STEM FROM LOW BASAL METABOLLIC RATE.

Deepening voice – cartilage vibrations slow down.

Depression and tiredness.

Cold intolerance.

Weight gain with reduced appetite.

Constipation.

Bradycardia.

Weakness.

Eventual myxoedema coma – BMR falls so much, the brain can’t function, body temperature goes down, and patient gets unconscious (patients are usually elderly, obese females).

Question 35

Why is it important to treat hypothyroidism? (x3)

Answer 35

Important because patients will die, they will perform poorly (because of low BMR), and cholesterol builds up (because of low BMR) which can cause heart disease.

Question 36

How is hypothyroidism treated?

Answer 36

Replace thyroxine with a tablet. It’s 100% treatable!!!

Question 37

What happens in relation to the HPT axis with hyperthyroidism? (x3) Hence, alternative name?

Answer 37

TSH and TRH levels fall to close to zero. You have an overactive thyroid and thyroxine levels are high = thyrotoxicosis (just another name for hyperthyroidism).

Question 38

What are the clinical features of hyperthyroidism? (x1 main feature) (x8 (x1 exception))

Answer 38

BMR GOES UP – AS WITH HYPO, THIS IS THE BASIS OF PRETTY MUCH ALL OTHER SYMPTOMS.

Temperature goes up.

Burn up calories – so feel very hungry and eat a lot but still lose weight. (Some do gain weight though from complete overcompensation of appetite.)

Increased heart rate – palpitations (can feel heart beating).

Feel tired – but sleeplessness in spite of this.

Myopathy (feeling weak) – lose muscle because burning so many calories.

Mood swings and irritability.

Frequent bowel movements – diarrhoea.

Hand tremors – couldn’t be calm.

Question 39

List a major cause of hyperthyroidism.

Answer 39

Graves’ disease.

Question 40

What is Graves’ disease?

Answer 40

Autoimmune disease where the whole gland is smoothly enlarged and the whole gland is overactive.

Question 41

What are the features of Graves’ disease? (x3)

Answer 41

Goitre - big thyroid gland and lump at neck. This is what causes the HYPERTHYROIDISM part of Graves’ disease.

Sore eyes.

Growth of the shins = pretibial myxoedema (second, different definition of myxoedema).

Question 42

What is the pathophysiology of hyperthyroidism in Graves’ disease?

Answer 42

Antibodies bind to and stimulate TSH receptor in the thyroid – hence, overproduction of thyroxine = hyperthyroidism. Results in goitre (enlarged thyroid).

Question 43

What is the pathophysiology of sore eyes in Graves’ disease? Name for this?

Answer 43

Another set of antibodies (different to the ones that cause goitre) bind to muscles behind the eye. Sore eyes are called exophthalmos.

Question 44

What is the pathophysiology of pretibial myxoedema in Graves’ disease?

Answer 44

Another set of antibodies stimulate growth of the shins. Leads to swelling of the soft tissue in the ankles and shins – HYPERTROPHY.

So, there’s essentially three separate autoimmune components to Graves’ disease.

Question 45

What would blood tests show for primary and secondary hypothyroidism: TSH, T4 and T3?

Answer 45

Primary: TSH UP, T4 and T3 DOWN. SECONDARY: TSH DOWN, T4 and T3 DOWN.