MEH - The Thyroid

Question 1

Where is the thyroid gland located?

Answer 1

Against and around the front larynx and trachea, below the thyroid cartilage. The isthmus extends from the 2nd to the 3rd rings of the trachea.

Question 2

Describe the embryological development of the thyroid

Answer 2

• first endocrine gland to develop
• at 3-4 weeks gestation, appears as an epithelial proliferation in floor of pharynx at base of tongue
• descends as diverticulum through thyroglossal duct and migrates downwards, passing in front of the hyoid bone
• remains connected to the tongue by the thyroglossal duct which subsequently degenerates
• detached thyroid then continues to its final position over next two weeks

Question 3

What are thyroid follicles made of?

Answer 3

Follicular cells arranged in spheres, filled with ‘colloid’ - a deposit of thyroglobulin

Question 4

What do thyroid follicular cells produce?

Answer 4

Thyroid hormone

Question 5

What do thyroid parafollicular cells produce?

Answer 5

Calcitonin

Question 6

What are the histological differences between the parathyroid gland and the thyroid gland?

Answer 6

Parathyroid gland tissue appears denser, lots of small cells stuck together. Thyroid gland tissue has spaces in it, and is made of thyroid follicles which have colloid in them

Question 7

At a molecular level, what are thyroid hormones formed from?

Answer 7

2 tyrosine linked together, with iodine at three or four positions on the aromatic rings

Question 8

What is the difference between T3 and T4?

Answer 8

T3 (triiodothyronine) is formed from monoiodotyrosine and diiodotyrosine, while T4 (tetraiodothyronine/thyroxine) is formed from two diiodotyrosine molecules

Question 9

What is the role of thyroglobulin in thyroid hormone formation?

Answer 9

It acts as a scaffold, stabilising tyrosine residues while they are iodinated and coupled

Question 10

What are the three reactions regulated by thyroid peroxidase?

Answer 10

1) oxidation of iodide to iodine (requires hydrogen peroxide)
2) addition of iodine to tyrosine acceptor residues on thyroglobulin
3) coupling of MIT or DIT to generate thyroid hormones within thyroglobulin protein

Question 11

How does dietary iodine reach the thyroid gland, where 95% of the iodine in the body is stored?

Answer 11

• reduced to iodide before absorption in the small intestine
• iodide is taken up from the blood by thyroid epithelial cells, which have a sodium-iodide symporter

Question 12

What form is most of the thyroid hormone secreted by the body?

Answer 12

90% is T4.

Question 13

Where is T4 converted to T3?

Answer 13

Liver and kidneys

Question 14

Which is stronger, T3 or T4?

Answer 14

T3 is three times stronger than T4

Question 15

How are T3 and T4 transported in the blood?

Answer 15

They are transported bound to the protein thyroxine-binding globulin

Question 16

How is thyroid hormone secretion regulated?

Answer 16

Via negative feedback of thyroid hormone to the hypothalamus and anterior pituitary

Question 17

What is thyroid stimulating hormone (TSH)?

Answer 17

A glycoprotein hormone composed of two non-covalently bound subunits (alpha and beta). The alpha subunit is also present in FSH and LH but the beta subunit is unique. It triggers thyroid hormone release.

Question 18

Give some examples of things stimulated by TSH

Answer 18

• iodide uptake and oxidation
• thyroglobulin synthesis and iodination
• colloid pinocytosis into the cell
• proteolysis of thyroglobulin
• cell metabolism and growth

Question 19

What are the two TSH induced second messenger pathways?

Answer 19

• can stimulate G alpha-S, increasing adenylyl cyclase and cAMP, producing more PKA leading to stimulation of thyroid hormone synthesis and release
• can stimulate G alpha-Q, increasing phospholipase C and therefore DAG and IP3. This leads to more Ca2+ release via the IP3 receptor, and PKC activation. This stimulates more thyroid hormone synthesis and release

Question 20

How do thyroid hormones stimulate the metabolic rate?

Answer 20

• increase number/size of mitochondria
• stimulate the synthesis of enzymes in the respiratory chain
• stimulates lipolysis and beta-oxidation of fatty acids
• stimulates insulin-dependent entry of glucose into cells and increases gluconeogenesis and glycogenolysis

Question 21

What are the sympathomimetic effects of thyroid hormone?

Answer 21

Increases target cell response to catecholamines by increasing receptor number on target cells

Question 22

What are the effects of thyroid hormone on the cardiovascular system?

Answer 22

• increases heart’s responsiveness to catecholamines
• increases cardiac output (higher heart rate and force of contraction)
• increase in peripheral vasodilation to carry extra heat to body surface

Question 23

What are the effects of thyroid hormone on the nervous system

Answer 23

Increases myelination of nerves and development of neurons

Question 24

True or false - thyroid hormone receptors are nuclear receptors?

Answer 24

True

Question 25

How do thyroid hormone receptors work?

Answer 25

• lipid soluble hormone enters cell through thyroid hormone transporters
• thyroid hormone receptor is pre-bound to hormone response elements in promoter region of thyroid hormone regulated genes
• hormone enters nucleus and bind to thyroid hormone receptor on DNA, relieving repression of gene transcription and allowing gene to be expressed
• expression of new protein mediates effects of thyroid hormone

Question 26

What unit is used when referring to normal plasma levels of thyroid hormones?

Answer 26

Picomoles

Question 27

What is goitre?

Answer 27

Enlargement of the thyroid gland which often develops when the thyroid gland is overstimulated

Question 28

Give some general symptoms of hypothyroidism

Answer 28

• obesity
• lethargy
• intolerance to cold
• bradycardia
• dry skin
• alopecia
• hoarse voice
• constipation
• slow reflexes
• low T3, low T4 and elevated TSH

Question 29

Give some symptoms of cretinism

Answer 29

• dwarfed stature
• mental deficiency
• poor bone development
• slow pulse
• muscle weakness
• GI disturbances

Question 30

Give some symptoms of myxedema

Answer 30

• thick puffy skin
• muscle weakness
• slow speech
• mental deterioration
• intolerance to cold

Question 31

What is Hashimoto’s disease?

Answer 31

Autoimmune disease leading to destruction of thyroid follicles. Causes hypothyroidism - most common disease of thyroid gland.

Question 32

How is Hashimoto’s disease treated?

Answer 32

Oral thyroid hormone - T4 is used since it has a longer half-life

Question 33

Give some general symptoms of hyperthyroidism

Answer 33

• weight loss
• irritability
• heat intolerance/sweating
• tachycardia
• fatigue, weakness
• increased bowel movements and appetite
• tremor of outstretched hands

Question 34

What is Graves’ disease?

Answer 34

Autoimmune disease resulting in hyperthyroidism, caused by production of ‘thyroid stimulating immunoglobulin’ which continuously stimulates thyroid hormone secretion outside normal negative feedback control

Question 35

Give some symptoms of Graves’ disease

Answer 35

• increase in BMR
• excessive sweating
• decrease in body weight
• muscle weakness
• heart palpitations
• bulging eyes (not always)

Question 36

Why is technetium-99m often used for isotope scanning of the thyroid with a gamma camera?

Answer 36

It has a biological half-life of around a day, so the radiation exposure is therefore low

Question 37

How does carbimazole treat an overactive thyroid?

Answer 37

It is a pro-drug which is converted to methimazole in the body. This prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin.