Thyroid hormone physiology Flashcards
Thyroid gland cells
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
Hormones secreted by the thyroid gland
Primary hormones secreted are iodothyronine (T3) and tetraiodothyronine (T4, thyroxine) and calcitonin
MIT and DIT
Rapidly degraded by halogenases to free the iodide
Iodide then re-utilised by combination with thyroglobulin
Distribution of T3 and T4
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
What do deiodinase enzymes do?
In target tissues convert the T4 to either T3 (80%) or reverse T3 (20%)
Biological activity of T3
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
Plasma half lives
T4: 6-8 days
T3: 1 day
Derbyshire neck
Swelling/ enlargement of the neck
Due to enlarged thyroid gland
Thyroid hormone solubility
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
Receptors for thyroid hormones
Intracellular
Nuclear
Interaction of hormone and receptor influences gene transcription and thus protein synthesis
Main effect of the thyroid hormone
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
Aspects of carbohydrate metabolism increased by thyroid hormones
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
Organs where oxygen consumption is not increased y thyroid hormones
Brain
Uterus
Testes
Spleen
Thyroid gland
Anterior pituitary gland
Levothyroxine
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
Adverse effects of levothyroxine
At excessive doses: palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss
Carbimazole and methimazole
Anti-thyroid drugs
Inhibit the synthesis of thyroid hormones by preventing the incorporation of the iodide into the thyroglubulin
Propylthiouricil
Prevents the peripheral conversion of T4 to T3
Potassium perchlorate
Acts by competing with iodide for the active iodide uptake pump
Alternative to surgery
Use of radioactive iodine
Selectively concentrated in the thyroid gland where it causes tissue damage and therefore reduced thyroid hormone secretion
Carbimazole
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
Adverse effects of carbimazole
Rashes and pruritis- often treated with antihistamines
Most serious side effect is neutropenia and agranulocytosis
Teratogenic
Propylthiouracil
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
Adverse effects of propylthiouracil
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
Prophylactic administration of iodine
Either by injection or incorporation into table salt or flour has markedly reduced incidence of endemic goitre worldwide
Drugs which can induce goitre
Lithium which is used in the treatment of bipolar depression
Iodides which are contained in vitamin preparations and some cough remedies
