Thyroid Gland Flashcards
What is hypothyroidism? What are its symptoms?
What is myxedema coma?
What’s the therapy for hypothyroidism?
Hair loss - receding hairline, swollen face, overgrown / dystrophic nails, swollen, very dry skin
Myxedema coma - severe untreated hypothyroidism
Oral thyroid hormone replacement - hairline back, swolleness gone, dry skin gone etc.
Where is the thyroid gland? Label onto the diagram:
What does the thyroid gland look like and what are the lobes separated by?
What is the name of an extra lobe carried by some people?
What are the thyroid hormones it releases?
In the neck, covered by the thyroid cartilage
It is like a butterfly gland made up of 2 lobes - the isthmus separates the two lobes
Pyramidal lobe - embryological reminent, not everyone has it
T3 and T4 (T4 predominantly)
What is the thyroid gland made up of? (i.e the follicles and their 2 different parts)
What type of cells are found in the thyroid gland?
What are parafollicular cells responsible for?
Made up of multiple follicles, they are like spheres (called the colloid) containing sticky, mucous-like, extracellular fluid; and are surrounded by multiple individual follicular cells
Follicular cells and parafollicular cells
PC - secrete calcatonin, important in calcium metabolism
To what other structures is the thyroid gland close to? Fill in the labels on the diagram:
What are parathyroid glands important for?
4 parathyroid glands that are embedded into the thyroid gland: 2 on each lobe - superior and inferior parathyroid glands
Recurrent laryngeal nerve - supplies the vocal cords, so damage to this nerve can interfere with the voice
Parathyroid glands are important for calcium metabolism - if these are removed or damaged during an operation, it will affect calcium levels in the body
How does the thyroid gland develop?
What are some issues during thyroid gland development?
Originates from the floor of the pharynx (base of the tongue), develops into the thyroglossal duct from which the thyroid tissue descends along, and then divides into 2 lobes. Duct disappears leaving the foramen caecum, its final position is complete by week 7, from which the actual gland develops
Thyroid gland can stop developing at any of these points - may not develop at all, or not descend completely etc.
Identify the different structures in the microscopic slide showing the thyroid gland:
Where is the thyroid hormone being made?
Follicular cells sit around the outside, colloid in the centre (sticky mucous)
Colloid = sticky mucus in which the thyroid hormone made here, and then carried away in the capillaries
How is the thyroid hormone actually made?
Important points to cover: TSH, TSH receptor, iodine, iodide, thyroglobulin, tyrosine, iodination, TPO, MIT, DIT, T3 and T4
Prompts:
What 3 things does the binding of TSH to the TSH receptor promote?
Which ion is important?
What does the ion bind to, to form MIT and DIT?
Colloid in the middle, follicular cells around the outside
TSH receptors are found on the cell membrane of the follicular cells
TSH released from the anterior pituitary gland, travels via the bloodstream and binds to TSH receptor on the follicular cell
Iodide ions (I-) also arrive via the bloodstream, and transported into the follicular cell via the sodium iodide transporter, crosses the cell and enters the colloid eventually
The I- that is now in the colloid is oxidised to make iodine
The binding of the TSH also stimulates the production of thyroglobulin, a pro-hormone that has tyrosine residues within its structure, and tyrosine has the capabilities of being iodinated
The binding of the TSH onto the receptor also activates the enzyme thyroperoxidase (TPO), which also travels into the colloid to catalyse the iodination reactions between the tyrosine residues and iodine
Iodine sticks onto the tyrosine residues, forms monoiodothyrodine (MIT) and di-iodothyrodine (DIT)
Different combinations of MIT and DIT joining together form T3 and T4, the thyroid hormones, which move back into the follicular cell, are released and then enter bloodstream
Which ion is essential for thyroid production?
Which of the thyroid hormones is more active than the other? And why is more T4 made than T3?
Where do T3 and T4 act and what is their function?
Iodide (I-)
T3 is more active than T4 - but more T4 is made (80%) as it is more stable and so better at circulation, and cells contain deiodinase enzymes that are able to convert T4 to T3
T3 and T4 act on all cells, they enter the mitochondria within the cells and increase the metabolic rate of the cells so more ATP is produced - cellular activity increases
What is the stucture of tyrosine?
Tyrosine can make which 2 products? What are their structures?
If these 2 products are then combines, what is made and what is it’s structure?
How is thyroxine (T4) produced?
Amino acid with aromatic ring - this is the part of thyroglobulin that undergoes iodination
3-Monoiodotyrosine (MIT)
3,5-diiodotyrosine (DIT)
3,5,3’-tri-iodothyronine (T3)
By combining 2 di-iodothyrosines (DITs) together - forms 3,5,3’,5’-tetra-iodothyronine (T4)
What is important about T3 and where the iodine binds?
Position of where the iodine binds, it can form active T3 or can form reverse T3, which is an inactive version of T3
What is T4 often referred to as? How can T3 be made from T4?
What does T3 provide in cells?
Pro-hormone, can be converted to T3 using the deiodinase enzyme found in almost every cell (takes an iodine molecule off the T4 molecule)
Almost all the thyroid activity in body cells as it is the more active form
How do they thyroid hormones travel around the body?
By binding to plasma proteins e.g.
Most common = thyroid-binding globulin (TBG), a plasma protein found in circulation to carry the thyroid hormone around
Rest of thyroid hormone is bound to albumin / pre-albumin
Almost all thyroid hormone is bound and so inactive, v. small amount active in circulation (less than 1%)
How does T3 and T4 effect gene expression?
T3 and T4 enter the cell via their respective receptors
T4 is then activated by the deiodinase enzymes (found in the target cells) to form T3
All the T3 enters the nucleus, where it binds to the thyroid hormone receptor in the nucleus
Results in altering gene expression
What are important mechanisms / actions of the thyroid hormone (esp. in foetuses)?
What is congenital hypothyroidism?
What TFT (thyroid function test) can be used to measure TSH levels (in newborns), and what results lead to hypothyroidism diagnosis?
Fetal growth and development (esp. to develop the CNS / brain) - foetus takes thyroid hormone from mother across the placenta, to ensure normal foetal growth
Baby born cannot form / produce its own thyroid hormone - results in cretinism
Heel prick test (around day 5) - looks for TSH levels in the blood, high TSH = baby is not producing enough of its own thyroid hormone
What are the actions of the thyroid hormone outside fetal development?
Increases basal metabolic rate - amount of energy / calories each cell in the tissue requires to function
Can affect carbohydrate, protein and fat metabolism (nutrients)
Can also affect the sympathetic nervous system e.g. increasing cardiac output - tachycardia etc.
Affects organs systems, speed of gut / bowel movement
Women can lose their period / suffer from infertility due to abnormal (usually low) thyroid levels
What controls thyroid hormone production?
Hypothalamus - produces TRH (thyrotrophin releasing hormone)
TRH travels via portal system to the anterior pituitary
Stimulates anterior pituitary’s thyrotroph cells to release TSH (also known as thyrotrophin)
TSH enters systemic criculation til it arrives at the thyroid
Results in production of T3 and T4 from the thyroid gland
Negative feedback loop - T3 and T4 then affect the hypothalamus to release less TRH, so less TSH is produced, so less T3 and T4 is produced
What impacts T3 and T4 production?
Negative feedback loop
Somatostatin (hormone) - negatively inhibitis TSH production from the anterior pituitary
Large amount of KI consumption, switches off T3 and T4 hormone production - given to patients with hyperthyroidism
Why is thyroid disease more common in women?
Women:Men = 4:1
To do with autoimmunity (probably) - adaptations acquired from pregnancy etc., acquiring Abs from foetuses
Autoimmune condition, where Abs may be destroying / affecting the thyroid gland
Is an overactive (hyperthyroidism) or underactive (hypothyroidism) more common?
The same
What is primary hypothyroidism?
What are the common causes and how does it present clinically?
The levels of which molecules do blood tests measure to diagnose hypo/hyper-thyroidism?
Underactive thyroid gland
Autoimmune damage to the thyroid or from surgery - causes thyroxine levels to decline and TSH climbs, this is because of the negative feedback loop - body releases more TSH to try to stimulate more T3 and T4 production
Blood tests tend to measure TSH and T4 levels
What are the names of the commonest forms of autoimmune thyroid disease?
If a patient already has a different / unrelated autoimmune condition or a family history of a different / unrelated autoimmune condition, is this relevant for thyroid issues?
Hashimoto’s thyroid disease - results in underactive thyroid
Grave’s disease - results in overactive thyroid
Yes, even if the autoimmune condition is unrelated, people who have one autoimmune condition tend to be susceptible to other autoimmune conditions
What are some symptoms in someone with hypothyroidism?
Tiredness / fatigue
Weight gain
Depression
Deepening voice
Problems with periods
Swelling of the face
Constipation
Goitre - enlargement of the thyroid gland
Bradycardia
Eventually resulting in myxedema coma
From tutorial:
Hypothyroidism - weight gain (overweight, BMI over 30 = obese), intolerance of the cold (shivering mechanism is not effective), lack of energy, constipation (reduced cellular activity = gut smooth muscle working less quickly / effectively), heavy periods, slightly lower pulse than normal
Essentially, all symptoms are due to reduced cellular activity leading to reduced efficiency
What pharmacological treatment is given for hypothyroidism?
Levothyroxine - tablet that replaces thyroid hormone (T4 form); rarely give thyroid hormone replacement intravenously, unneccessary unless an emergency / urgent
Deiodinase enzymes found naturally in the body convert it to T3
T3 is the active version so why is T3 not given instead of T4?
No added benefit, more expensive, body already contains the enzymes that can convert the T4 to T3
T4 is more stable and so better at circulation
What is the treatment for hyperthyroidism?
How are the doses adjusted?
Complications with levothyroxine?
Firstly, give an anti-thyroid drug to block / stop all thyroxine production, then give them levothyroxine to replace the thyroxine levels needed back
Adjust dose according to TSH levels, give a dose for a few months, blood test to look at TSH levels again, aim to get TSH levels back into the normal range
With too much thyroid hormone replacement: Weight loss, headaches, tackycardia, heart attack
What is combined thyroid hormone replacement?
If a patient takes T3 alongside the T4 prescribed by the doctors without consulting the doctor first, what issues can arise?
Taking T4 and T3 to replace their thyroid hormones, rather than just T4
Toxicity - palpitations, tremors, anxiety etc.
What is hyperthyroidism?
What are its causes and how does it present?
Thyroid makes too much thyroid hormone
Can be caused by Grave’s disease, an autoimmune condition where the thyroid gland is enlarged and produces too much thyroxine; toxic multinodular goitre, development of many nodules which release too much thyroid hormone; or solitary toxic nodule, one nodule that overproduces thyroid hormone
Clinically, results in increased thyroxine levels, and TSH levels drop
What is Grave’s disease?
How does this present clinically? What are the symptoms?
Autoimmune disease - caused by Abs that are able to bind and stimulate TSH receptors in the follicular cells in the thyroid. TSH receptor should normally only respond to TSH, but as it can also be stimulated by these Abs, this disrupts the negative feedback loop
Presents as a smooth goitre - enlarged thyroid gland (looks like a bulging / enlarged neck), does not have multiple nodules, smooth = whole thing is enlarged
Other Abs bind to muscles behind the eye - causes bulging eyes (exophthalmos)
Other Abs stimulate growth of soft tissue of shins - pretibial myxoedema
What are some symptoms of hyperthyroidism?
Agitation
Weight loss despite increased appetite
Diarrhoea
Heat intolerance - constantly feeling hot
Goitre
Heart palpitations - inetreferes with sympathetic nervous system, tackycardia / arrythmia - risk of heart attack
Constipation
Weak muscles
Sore eyes
Hairloss
