Session 10 - Lecture 1 - Thyroid Gland Flashcards
1 - Title
The Thyroid gland
“Looking at: thyroid gland, thyroid hormones and physiological role of thyroid hormone, then clinically orientated lecture on thyroid disease and dysfunction. So this morning, just going to introduce the underlying physiology and basics to allow you to understand the clinical application Prof London will tell you about”
2 - Learning outcomes
- Describe the LOCATION and STRUCTURE of the thyroid gland.
- Outline the overall structure of T3 & T4 and the mechanisms of their PRODUCTION, STORAGE and secretion.
- Describe how the ACTIVITY of the thyroid gland is controlled.
- Describe the EFFECTS OF THYROID HORMONES on cells and the body as a whole.
- Describe the consequences of over- and under-secretion of thyroid hormones
3 - The Thyroid gland
- Lies against and around front larynx and trachea
- BELOW thyroid cartilage (Adam’s apple)
- Isthmus extends from 2nd to 3rd rings of the trachea
- 2 lobes joined by ISTHMUS
- “Bow tie” shape and location
- Parathyroid and thyroid are DISTINCT glands
- Thyroid cartilage
- RIGHT LOBE
- ISTHMUS
- Trachea
- Hyoid bone
- Cricoid cartilage
- LEFT LOBE
- C7
- Parathyroid glands
- Esophagus
- Trachea
- Pharynx
- Thyroid gland
- Carotid artery
“So, I’m sure we’ve all got a broad idea of the location of the thyroid gland in the neck – its shape is approx. like a bow-tie, and it’s also situated where you wear a bow-tie, as clinicians, that description isn’t sufficient – need to be more accurate in our location of the thyroid gland, so if you feel that protrusion in your neck, your Adam’s apple, that is your thyroid cartilage, feel the notch, go down to first notch underneath that, what you’re feeling underneath that is the cricoid cartilage, goes all the way around the trachea, 360 circumference, thyroid cartilage just on anterior portion, and below, sitting on top of cricoid cartilage and between suprasternal notch, feel suprasternal notch, that is the location of your thyroid gland. And, one anatomical feature as clinicians you should be aware of is this membrane between the thyroid cartilage and cricoid cartilage – reason should be aware of that, if ever a scenario where you have to perform an emergency cricothyroidotomy, may have seen it on the media or ER for example, the old television series M.A.S.H. sometimes you see it on the newspapers, someone on an aeroplane, choking, no way to create an airway – so it’s a last resort emergency procedure, not routine, but as a last resort to get an airway in, need to be aware of this membrane here, feel for that gap for thyroid and cricoid cartilage, with pen knife make an incision through membrane, then insert a tube such as outer tube in a ball point pen or a straw or something like that (if not in hospital setting) – but it is definitely a last resort emergency procedure. So our thyroid gland consists of 2 lobes, a left and a right lobe, and in human, these 2 lobes are joined by a structure called the isthmus – other animals have 2 separate thyroid glands and no isthmus – but we have this joined structure. In terms of anatomical relationship there’s another gland we need to be aware if which is the parathyroid glands (PTG) – typically in textbooks, show you we have 4 PTG, in reality there is some anatomical variation, can have 1, 2 or even 6 of the glands, don’t necessarily have to be embedded in the thyroid glands, but in most people, PTG, anatomical location as can see in this diagram here is embedded within thyroid gland, PTG responsible for secreting, as the name suggests, PT hormone responsible for calcium homeostasis (Dr Hudman, next week).”
4 - Embryological development
Embryological development
• Thyroid is FIRST endocrine gland to develop.
• At ~3-4 weeks gestation, thyroid gland appears as an EPITHELIAL PROLIFERATION in floor of pharynx at BASE of the TONGUE and the takes several weeks to migrate to final position.
• First descends as diverticulum through THYROGLOSSAL DUCT and migrates downwards passing in front of hyoid bone.
• During migration remains connected to tongue by thyroglossal duct which subsequently DEGENERATES
• Detached thyroid then continues to its final position over following two weeks.
- Foramen cecum
- Oral cavity
- Future tongue
- Thyroid diverticulum
- Thyroglossal duct
- Developing hyoid bone
- Esophagus
Week 4: Thyroid diverticulum forms. - Foramen cecum
- Tongue
- Thyroglossal duct
- Thyroid gland
- Hyoid bone
- Oesophagus
- Trachea
“So just a little bit about the embryological development of the thyroid gland – it is the first endocrine gland to develop during embryogenesis, and at about 3-4 weeks of gestation, the cells that will form the thyroid gland will appear as this proliferation of epithelial cells at the base of the tongue. So the TG actually originates as the cells that are going to form the future tongue. But then it takes this journey and descends as a diverticulum through this duct called the thyroglossal duct, and it migrates then and joins the hyoid bone – descends towards the hyoid bone, and then the thyroglossal duct degenerates and the cells that form the thyroid gland continue the journey to work the final location, so it does have some clinical implications that I’m sure Prof London will highlight to you later on, sometimes cells won’t complete the journey so you can get tissue forming where it shouldn’t, forming things such as thyroglossal cysts.”
5 - Histology of thyroid tissue
Histology of thyroid tissue
• Follicular cells arranged in SPHERES called THYROID FOLLICLES
• Follicles filled with COLLOID, a deposit of thyroglobulin
• Colloid is “EXTRACELLULAR” even though it is inside the follicle
- Follicular cells
Colloid
“So if we’re thinking about the cells of the thyroid gland, an important structure in the thyroid are these thyroid follicles, and these are v important bc they contain the protein called colloid, and that is essentially a store of the protein thyroglobulin, which is where thyroid hormones are made (we will go through that step by step) – have a concept of colloid which is made by … they’re spherical structures surrounded by follicular cells, so although colloid is even inside structures it’s considered extracellular rather than intracellular. Obviously we’re looking at 2D structure here, but in reality they’re 3D structures – so blow this balloon up – air inside balloon is colloid, rubber is follicular cells, so imagine now how colloid is extracellular – extracellular fluid here, rubber of balloon is follicular cells and inside spherical structure is the colloid which is composed of the protein thyroglobulin.”
6 - The thyroid and parathyroid glands
The thyroid and parathyroid are DISTINCT glands
Parathyroid gland
- Parathyroid PRINCIPAL cells also called CHIEF CELLS produce PARATHYROID HORMONE
Thyroid gland
- Thyroid FOLLICULAR cells produce THYROID HORMONE
- Thyroid PARAFOLLICULAR cells produce CALCITONIN.
- COLLOID stores THYROGLOBULIN
- Histological section through thyroid gland in the location of one of the parathyroid glands. Cells from BOTH GLANDS are present in the section.
“And this is quite an unusual histological section but it’s a v nice one bc it’s caught both glands, got PTG on left and TG on right, so a normal section of TG have to be v lucky to get both tissues on both section, but this section does show this and illustrates q nicely the diff cell types that are relevant. In our PTG, important endocrine cells there are called principal cells, see some textbooks refer to those called chief cells, producing PTH essential for calcium homeostasis. In the thyroid gland itself, we can see the follicular cells, I was demonstrating to you with the balloons, so using analogy of balloons, follicular cells will be rubber of balloon, and inside will be the colloid (air inside balloon) – forming spherical structures, and its follicular cells producing protein thyroglobulin from which thyroid hormone is derived. Also have another type of cell in TG (covered next week in calcium homeostasis) and that’s the parafollicular cells responsible for producing calcitonin rather than thyroid hormone, follicular cells surrounding spheres of colloid.”
7 - Thyroid hormones
Thyroid hormones
2 tyrosines linked together with iodine at three or four positions on the aromatic rings
Monoiodotyrosine MIT [1 iodine on aromatic ring of tyrosine] + Diiodotyrosine DIT [2 iodines on aromatic ring of tyrosine] –> T3= Triiodothyronine [3 iodines in tyrosine coupling reaction]
Diiodotyrosine DIT + Diiodotyrosine DIT –> T4= Tetraiodothyronine (thyroxine) [4 iodines in tyrosine coupling reaction]
“So, how are thyroid hormones produced? They’re produced by iodinating tyrosine residues – and these are tyrosine residues that are part of the protein thyroglobulin, so follicular cells producing this protein, exporting it into colloid, and in colloid, the tyrosine residues are iodinated. So tyrosine iodination occurring can either be 1 iodine group added to the aromatic ring – MIT, or 2 iodine groups added which is DIT (1 or 2), and then those 2 tyrosines in a coupling reaction are linked together and when they’re cleaved from the protein, will eventually form either T3 (MIT + DIT combined) – combine to form T3 – just count the iodines, T4 or thyroxine tetraiodothyronine – that would be formed by coupling of 2 DIT – so 4 iodines. So these coupling reactions form either T3 or T4.”
8 - Thyroglobulin
Thryoglobulin acts as a scaffold on which thyroid hormones are formed
- Tyrosine residues within thyroglobulin [2 tyrosine resides on thyroglobulin]
- Thyroglobulin protein [backbone]
- Thyroglobulin protein contains 134 tyrosines, although only a handful of these are actually used to synthesize T4 and T3.
–Iodination–>
[1 or 2 I’s on each tyrosine]
–Coupling–>
[Iodinated tyrosines on one side]
“And these as I mentioned in previous slide, these are occurring on tyrosine residues within this protein thyroglobulin (134 tyrosine residues in thyroglobulin protein, and only a handful of those used in iodination reactions). So once iodination occurs, then this coupling occurs to link 2 tyrosines together, and whether that will ultimately be T3 or T4 will depend on the combination of MIT or DIT.”
9 - Thyroid Peroxidase
Thyroid Peroxidase
Membrane bound enzyme that regulates 3 separate reactions involving iodide
1) OXIDATION of Iodide to Iodine (requires the presence of H2O2)
2) ADDITION OF IODINE to tyrosine acceptor residues on the protein throglobulin
3) COUPLING of MIT or DIT to generate thyroid hormones within the thyroglobulin protein
“Now, a critical enzyme in facilitating these processes is the enzyme thyroid peroxidase, and this enzyme has 3 v important functions in the generation of thyroid hormone: firstly, it oxidises iodide to iodine, and this is an essential step bc it’s iodine that’s being added to tyrosine residues, but we’re absorbing it in the form of iodide, so iodide needs to oxidised to iodine, first function of thyroid peroxidase. Also important to add iodine, therefore facilitates iodinating reaction, and also enzyme that does coupling of 2 iodine tyrosine residues together, so all 3 of these steps are absolutely essential and critical for the generation of thyroid hormone.”
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