Thyroid hormone physiology

Question 1

Thyroid gland cells

Answer 1

The thyroid gland is composed of follicles each consisting of a monolayer of epithelial cells enclosing a large core of viscous, homogenous colloid

Colloid acts as a reservoir of thyroid hormone

Question 2

Hormones secreted by the thyroid gland

Answer 2

Primary hormones secreted are iodothyronine (T3) and tetraiodothyronine (T4, thyroxine) and calcitonin

Question 3

MIT and DIT

Answer 3

Rapidly degraded by halogenases to free the iodide

Iodide then re-utilised by combination with thyroglobulin

Question 4

Distribution of T3 and T4

Answer 4

T3 and T4 leave the follicular cells and enter the blood stream for distribution to the target tissues

Approximately 95% of the thyroid hormone leaving the thyroid gland is in the form of T4

Question 5

What do deiodinase enzymes do?

Answer 5

In target tissues convert the T4 to either T3 (80%) or reverse T3 (20%)

Question 6

Biological activity of T3

Answer 6

T3 is approximately 40 times more active than T4

Reverse T3 is biologically inactive

Up to 90% of the biologically active thyroid hormone in cells is in the form of T3

Question 7

Plasma half lives

Answer 7

T4: 6-8 days

T3: 1 day

Question 8

Derbyshire neck

Answer 8

Swelling/ enlargement of the neck

Due to enlarged thyroid gland

Question 9

Thyroid hormone solubility

Answer 9

Insoluble in water

Transported in blood bound to plasma proteins

Over 99% of circulating thyroid hormones are protein bound

Majority of T4 binding is to thyronine binding globulin (TBG)

15-20% T4 bound to thyroxine binding prealbumin (TBPA)

5-10% T4 is to albumin

Question 10

Receptors for thyroid hormones

Answer 10

Intracellular

Nuclear

Interaction of hormone and receptor influences gene transcription and thus protein synthesis

Question 11

Main effect of the thyroid hormone

Answer 11

Increase basal metabolic rate

• increased carbohydrate metabolism
• increased synthesis, mobilisation and degradation of lipids
• increased protein synthesis

Essential for normal development if CNS, especially myelination of nerve fibres

Question 12

Aspects of carbohydrate metabolism increased by thyroid hormones

Answer 12

Glycogenesis and glucose uptake by muscle cells and adipose cells

Potentiation of the effects of insulin

Potentiation of the effects of the catecholamines

Increase in glucose absorption by the GI tract

Question 13

Organs where oxygen consumption is not increased y thyroid hormones

Answer 13

Brain

Uterus

Testes

Spleen

Thyroid gland

Anterior pituitary gland

Question 14

Levothyroxine

Answer 14

Used to treat thyroid deficiency

Can be used to suppress TSH secretion in the treatment of some thyroid tumours

Can be given by mouth or injection

Question 15

Adverse effects of levothyroxine

Answer 15

At excessive doses: palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss

Question 16

Carbimazole and methimazole

Answer 16

Anti-thyroid drugs

Inhibit the synthesis of thyroid hormones by preventing the incorporation of the iodide into the thyroglubulin

Question 17

Propylthiouricil

Answer 17

Prevents the peripheral conversion of T4 to T3

Question 18

Potassium perchlorate

Answer 18

Acts by competing with iodide for the active iodide uptake pump

Question 19

Alternative to surgery

Answer 19

Use of radioactive iodine

Selectively concentrated in the thyroid gland where it causes tissue damage and therefore reduced thyroid hormone secretion

Question 20

Carbimazole

Answer 20

Used to treat hyperthyroidism

Pro-drug, after absorption it is converted to the active form- methimazole

Prevents peroxidase iodinating the thyrosine residues on thyroglubulin

Reduces the production of the thyroid hormones T3 and T4

Question 21

Adverse effects of carbimazole

Answer 21

Rashes and pruritis- often treated with antihistamines

Most serious side effect is neutropenia and agranulocytosis

Teratogenic

Question 22

Propylthiouracil

Answer 22

Used to treat hyperthyroidism

Inhibits thyroperoxidase, normally acts in thyroid hormone synthesis

Also inhibits tetraiodothyronine deodinase which converts T4 to T3

Drug of choice to treat hyperthyroidism in first trimester

Question 23

Adverse effects of propylthiouracil

Answer 23

Rashes and pruritis- often treated with antihistamines

Notable side effects include risk of granulocytosis and risk of serious liver injury, including liver failure and death

Question 24

Prophylactic administration of iodine

Answer 24

Either by injection or incorporation into table salt or flour has markedly reduced incidence of endemic goitre worldwide

Question 25

Drugs which can induce goitre

Answer 25

Lithium which is used in the treatment of bipolar depression

Iodides which are contained in vitamin preparations and some cough remedies