Thyroid Gland

Question 1

Where is the thyroid gland located, what is its structure and what it is attached to

Answer 1

Located in the neck, in front of the lower larynx and upper trachea. Formed of two lateral lobes joined by central isthmus

It is attached to the pre-tracheal fascia, with the thyroid gland moving upwards upon swollowing

Question 2

What two nerves lie in close proximity to the thyroid gland

Answer 2

Recurrent laryngeal

External branch of superior laryngeal

Question 3

Where are the parathyroid glands usually located and how many normally are there

Answer 3

Found embedded within the thyroid gland

Usually between 1-6 parathyroid glands

Question 4

What cells are found in the thyroid gland and how are they arranged

Answer 4

Follicular cells and parafollicular cells (C-cells)

Follicular cells are arranged into follicles separated by connective tissue with parafolliulcar cells found in the connective tissue

Follicles are spherical, lined by follicular (epitheial) cells surrounding a lumen containing colloid which is rich in thyroglobulin

Question 5

What hormones are produced in the thyroid gland and by which cells

Answer 5

Thyroxine and triiodothyronine are produced by follicular cells, derived from tyrosine

Calcitonin is produced by parafollicular cells, a polypeptide hormone

Question 6

What enzyme is involved in the synthesis of T3 and T4 and what is it involved in

Answer 6

Thyroid peroxidase:

Oxidises iodide to an iodinating species

Catalyses iodination of side chains of tyrosine

Catalyses coupling of iodated tyrosine species

Question 7

Describe the synthesis of T3 and T4

Answer 7

Iodide transported into follicular cell using sodium-iodide symporter

Thyroglobulin is synthesised in follicular cells and is then secreted into lumen of follicle

Iodide is oxidised to produce iodinating species, catalysed by thyroid peroxidase

Iodination of tyrosine side chains to produce MIT and DIT, catalysed by thyroid peroxidase

Coupling of DIT with MIT or DIT to produce T3 and T4, catalysed by thyroid peroxidase, this is done within thyroglobulin

Question 8

How are T3 and T4 secreted

Answer 8

Thyroglobulin is taken into follicular cells form the follicle lumen by endocytosis

Proteolytic cleavage occurs to relase T3 and T4 which then diffuse form the cells into circulation

Question 9

How is the secretion of thyroid hormone controlled

Answer 9

Hypothalamus releases TRH from cells in dorsomedial nucleus, under influence of circulating T3 and T4 levels, stress (increases release) and temperature (fall in temp, increases release)

Anterior pituitary releases TSH from thyrotropes, release stimulated by TRH. It is released in low-amplitude pulses in a diurnal rhythm, higher levels at night which decrease in early hours of the morning

Question 10

What are the actions of TSH

Answer 10

Increases vascularity, size and number of the follicle cells

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

Question 11

How are T3 and T4 transported

Answer 11

Bound to thyroxine binding globulin, pre-albumin and albumin

Question 12

How do oestrogens in pregnancy affect the levels of T3/T4

Answer 12

Oestrogens increase synthesis of TBG which decreases amount of T3/T4 in circulation

This causes more TRH and TSH to be produced, causing increased T3 and T4 secretion by the thyroid gland to bring amount of free T3/T4 to normal

However, there is an increased total T3/T4 in the blood

Question 13

What are the major physiological actions of T3/T4

Answer 13

Increase metabolic rate of tissues

Important for normal growth and development

Have sympthomimetic effects, mimicing the SNS actions

Question 14

How does T3/T4 increase the metabolic rate of tissues

Answer 14

Stimulates glucose uptake and metabolism

Stimulates mobilisation and oxidation of fatty acids

Stimulates protein metabolism

Increase size and number of mitochondria

Stimulate synthesis of enzymes in respiratory pathway

Question 15

What sympathomimetic effects do T3/T4 have

Answer 15

Increase target cell response to catecholamines by increasing receptor number

Cardiovascular system - increase heart rate and force of contraction, increase peripheral vasodilation (increase heat loss)

Nervous system - increase myelination of nerves, neurone development, hyperplasia of cortical neurons

Question 16

What happens when there is an absence of thyroid hormones in children and in adults

Answer 16

In absence from birth to puberty, children develop cretinism where they remain physically and mentally retarded

In adults, they develop poor concentration, poor memory and lack of initiative

Question 17

What are T3/T4’s mechanism of action

Answer 17

Thyroid hormone enters cell through thyroid hormone transporters

The receptor is pre-bound to specific DNA sequences, thyroid horomone response elements (TRE) in promoter region of thyroid hormone regulated genes

TRE’s bind in T3/T4 absence and usually cause transcription repression, with hormone binding associated with confromational change in the receptor, causing it to be expressed

Question 18

Where is T4 converted into T3 and why does this happen

Answer 18

Converted mostly by liver and kidneys by removal of 5’-iodide

This allows regulation of the amount of the active hormone as T3 has a greater activity than T4

Question 19

What is rT3 and how is it formed

Answer 19

Inactive reverse T3 (rT3) which binds to thyroid hormone receptors and acts as an antagonist, blocking T3 effect

It is produced by removal of 3’-iodide from T4