Thyroid Hormones and Anti

Thyroid Hormones and Anti-Thyroid Drugs
Synthesis, storage and secretion of thyroid hormones

The thyroid gland secretes 3 hormones
1. Thyroxine (T4)
2. T3
3. Calcitonin
T4 and T3 are essential for normal growth and development whilst also controlling metabolism
Calcitonin regulates calcium levels within the plasma and can be used to treat osteoporosis
Functional unit of a thyroid is the follicle, which consists of a single layer of epithelial cells around a cavity (follicle lumen).
The cavity is filled with thyroglobulin (thick colloid)
Thyroglobulin is a large glycoprotein and each molecule has 115 tyrosine residues
Thyroglobulin is synthesised, glycosylated and then secreted in the follicle lumen where the tyrosine residues are iodinated
A dense blood flow network surrounds the follicles and rate of blood flow through the gland is high in comparison to other
tissues
The main steps involved in synthesis, storage and secretion of thyroid hormone are:
1. Uptake of plasma iodide by follicle cells
2. Oxidation of iodide and iodination of tyrosine residues of thyroglobulin
Iodide uptake is an energy dependant process which occurs against a gradient

Iodide is captured from the blood and moved to the lumen by two transporters: the Na/I symporter (located at the
basolateral surface of thyrocytes) and pendrin (Na/Cl porter in the apical membrane)
The oxidation of iodide and incorporation into thyroglobulin is aided by thyroperoxidase (located on the inner surface of
the cell by the colloid). Reaction requires the presence of hydrogen peroxide as an oxidising agent
Iodination occurs after tyrosine has been incorporated into thyroglobulin.
Tyrosine residues are iodinated first at position 3 to form MIT and then can later be iodinated at position 5 to form DIT.
These molecules are then coupled in pairs. MIT+ DIT forms T3 and DIT + DIT forms T4
Mechanism for coupling is thought to involve a peroxidase system similar to the one used in iodination
The iodinated thyroglobulin of the thyroid forms a large store of thyroid hormone within the gland with a relatively slow
turnover in contrast to other endocrine secretions
Secretion of thyroid hormone
Thyroglobulin is taken up into the follicle cell by endocytosis

Endocytotic vesicles then fuse with lysosomes and proteolytic enzymes which act on thyroglobulin to release T3 and T4
into the plasma
The surplus MIT and DIT are released into the plasma too but are enzymatically degraded the iodine is scavenged for
further use
Regulation of thyroid function
TRH is released from the hypothalamus in response to various stimuli which in turn releases thyroid stimulating hormone (TSH) from
the anterior pituitary
TSH acts on the membrane receptors of the thyroid follicle cells and via a mechanism involving cAMP and PD3 kinase it has a
trophic effect on thyroid cells
o Leads to the increased transcription of iodine transporter genes which would therefore increase uptake of iodine
o Increased synthesis and secretion of thyroglobulin
o Increased production of hydrogen peroxide and increased iodination of thyroglobulin
o Endocytosis and proteolysis of thyroglobulin
o Secretion of T3 and T4
o Blood flow through the gland
TSH production is regulated via negative feedback of the thyroid hormones (T3 being more active than T4). The peptide
somatostatin also reduces TSH production
Plasma iodide concentrations also influence thyroid function. Reduced levels of iodine intake lead to reduced plasma iodide
concentration and therefore reduced hormone production and an increase in TSH levels and vice versa
Hyperthyroidism
Also referred to as thyrotoxicosis
XS activity of thyroid hormones resulting in a higher metabolic rate, increased body temp, weightloss and tachycardia
There are two types of thyrotoxicosis: diffuse toxic goitre (graves disease) and toxic nodular goitre
Diffuse toxic goitre organ specific autoimmune disease caused by autoantibodies targeting TSH which induces increased
thyroid production. There is also increased sensitivity to catecholamines
Toxic nodular goitre caused by benign neoplasm or adenoma

Drugs for hyperthyroidism:
Radioiodine given orally, taken up by the thyroid gland in a similar mechanism to normal iodine and damages cells via emitting
radiation to prevent further thyroid hormones being produced
Thioureylenes (e.g carbamipazole) decreases synthesis of thyroid hormones via inhibition of thyroperoxidase and therefore
reduces the iodination of thyroglobulin
Iodine given orally in huge doses to transiently reduce thyroid hormone secretion and reduce vascularity of the gland
Hypothyroidism
Decreased activity of the thyroid
Also referred to as myxoedema
Immunological in origin low metabolic rate, bradycardia, slow speech, lethargy and sensitivity to cold are symptoms
Hashimotos thyroiditis is caused by an immune response mounted against thyroglobulin
Treatment of thyroid tumours with radioiodine is also often a cause of hypothyroidism
The only effective treatment (if not caused by iodine deficiency) is to administer the thyroid hormones themselves during replacement
therapy.
Drugs for Hypothyroidism:
Levothyroxine orally administered. Has the actions of thyroxine as its a synthetic compound which resembles
structural similarities
Liothyronine has all the actions of endogenous tri-iodothyronine (T3) and is administered via IV

Thyroid Hormones and Anti

Uploaded by

Copyright:

Available Formats

Thyroid Hormones and Anti

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Thyroid Hormones and Anti

Uploaded by

Copyright:

Available Formats

Thyroid Hormones and Anti-Thyroid Drugs

Synthesis, storage and secretion of thyroid hormones

Iodide uptake is an energy dependant process which occurs against a gradient

Secretion of thyroid hormone

Thyroglobulin is taken up into the follicle cell by endocytosis

Regulation of thyroid function

Also referred to as thyrotoxicosis

Toxic nodular goitre caused by benign neoplasm or adenoma

Decreased activity of the thyroid

Also referred to as myxoedema

Hashimotos thyroiditis is caused by an immune response mounted against thyroglobulin

Treatment of thyroid tumours with radioiodine is also often a cause of hypothyroidism

You might also like