Thyroid Hormones Flashcards
Describe Myxoedema
The condition is diagnosed from a combination of abnormal thyroid function, physical examination findings of severe hypothyroidism, and altered mental status. Bradycardia, hypothermia, and hyponatremia are often present as well. Treatment is often administered intravenously, since there may be edema of the gut wall that limits oral absorption.
What hormones are associated with the thyroid glands
The iodothyronines:
Tri-iodothyronine (T3) and tetra-iodothyronine (T4, Thyroxine)
Also calcitonin is produced which is concerned with calcium metabolism.
What are the properties of these hormones
They are amines, and hence share a mixture of properties of both steroid and polypeptide hormones.
How many lobes does the thyroid have
2 lobes- left and right
Describe the general structure of the thyroid
Consists of single cell layers of follicular cells surrounding a central region filled with a yellowish protein rich gel called colloid. Between 20 and 40 follicles are grouped together by surrounding connective tissue to form lobules, each lobule receiving its own blood supply and having the ability to function independently of other lobules. Interspersed between the follicular cells are small clumps of very different cells called parafollicular cells.
What is the role of the parafollicular cells
These cells operate completely independently of the main thyroid tissue and produce calcitonin.
Describe how the follicles vary in shape and size depending on the degree of their stimulation
Highly active follicles consist of thick columnar follicular cells.
Relatively inactive cells would have thinner more cuboidal follicular cells
What separates the two lobes
The isthmus
What is found on top of the isthmus
The pyramid
How much does the adult thyroid gland weigh
Between 15-20g.
Where is the thyroid gland found
The trachea
Describe the uptake of inorganic iodide into the follicular cells
The concentration of inorganic iodide is greater in the follicular cell than it is in the general circulation.
Also the anion has to enter against its electrical gradient, as living cells have a negative interior with respect to the exterior.
Iodide therefore has to move against an impressive electrochemical gradient.
It does this by means of the sodium-iodide symporter (NIS) in the basolateral membrane which transports two sodium ions and one iodide ions into the cell down the sodium gradient. The energy needed to drive this process is provided by the Na+/K+ ATPase pump.
Describe Thyroglobulin synthesis
Binding of TSH to TSHR also stimulates the transcription of genes in the nucleus that will synthesise thyroglobulin. Thyroglobulin is a large glycoprotein homodimer. Thyroglobulin is secreted into the colloid through the apical membrane
How are the iodide ions transported into the colloid
They reach the apical membrane where they are transported into the colloid by the pendrin transporter
Describe the iodination and organification reactions that form mono- and di-iodotyrosines
Binding of TSH to TSHR also activates TPO.
Along the apical membrane colloid border the inorganic iodide gets oxidised to a highly active, short-lived form of iodide known as ‘reactive iodine’. This iodination reaction is catalysed by TPO (Thyroidal peroxidase) in the presence of hydrogen peroxide.
In this form it immediately gets ‘organified’ by binding to positions 1 and 2 of certain tyrosyls which are incorporated into the thyroglobulin, forming the mono- and di-iodotyrosyls (MIT and DIT).
Describe the coupling reaction
The thyroglobulin undergoes a configurational change, known as the coupling reaction, in which the molecule undergoes a structural realignment such that specific di-iodotyrosyls link up with either mono- or di-iodotyrosyls to form tri- and tetra-iodothyronines. This reaction is also under control of TSH.
How many thyronines are normally formed on each thyroglobulin
3-4
Where are the thyronines stored
In the colloid
Describe the uptake from colloid and release into circulation
Binding of TSH also results in the pinocytosis of the colloid, drawing bits of it back into follicular cells. Once the iodinated thyroglobulin is back in the follicular cell cytoplasm, it is taken up by lysosomes directed towards the apical membrane, also in response to TSH. These lysosomes contain various enzymes, including proteases and deiodinases, which break down the thyroglobulin, releasing iodine, tyrosine and thyronines. The iodine and tyrosine residues of MIT and DIT can be recirculated within the cell for reuse. T3 and T4 are secreted through the basolateral membrane into the circulation by means of a transporter mechanism.
Describe the transport of the iodothyronines in the blood
Mostly bound to plasma proteins
a) thyroid-binding globulin: TBG (70-80%) b) albumin (10-15%) c) prealbumin (aka transthyretin)
Only 0.05% T4 and 0.5% T3 unbound (bioactive components)
What is the main hormone product of the thyroid gland
T4
Describe the peripheral conversions of the iodothyronines.
T4 plays a role as a pro-hormone in addition to its direct role of a hormone itself. Numerous peripheral tissues contain deiodinases which can deiodinate T4 to the more bioactive T3 by the removal of the iodine atom at position 5’. However, a different deiodinase can deiodinate the 5’ of pro-hormone T4 to form rT3.
Describe the differences in metabolic activities of T4,T3 and rT3
While T3 is more biologically active than T4, rT3 is metabolically inactive. Under specific conditions peripheral tissues have the ability to direct the nature of the deiodination pathway depending on their environmental circumstances, either increasing or decreasing the biological activities associated with these thyroid hormones.
Describe the differences in half-life and latency periods of the thyroid hormones
Latent period:
T3: ~ 12h
T4: ~ 72h
Half lives:
T4 around 7-9 days
T3 around 2 days
