The Thyroid Gland Flashcards
What is the anatomy of the thyroid gland?
Sits in the neck below the thyroid cartilage (Adams Apple)
Two lives joined by the isthmus
Some people have a pyramidal section in the middle
What makes up the thyroid gland?
Lots of follicular cells arranged into spheres with colloid in the middle. Each of these is a follicle
The colloid is an extracellular fluid
There are also some parafollicular cells that produce calcitonin
Follicles are surrounded by lots of blood vessels
Which anatomical structures are anatomically close to the thyroid gland?
On the underside of the thyroid there are two pairs of parathyroid glands
The superior and inferior parathyroid glands. These produce parathyroid hormone which is important in the absorption of calcium
The recurrent laryngeal Nerva also runs close behind the thyroid gland. This supplies the vocal chords
What is the embryology of the thyroid gland? (How is it formed)
Midline outpouching from floor of pharynx (originated from base of tongue)
This develops into the thyroglossal duct
This divides into two lobes
The duct disappears leaving the foramen caecum
It is in its final position by 7 weeks
Then the thyroid gland develops
What are the thyroid hormones?
T3 - tri-iodothyronine
T4 - tetra-iodothyronine (aka thyroxine)
How are the thyroid hormones made?
TSH (from anterior pituitary) binds to TSH receptors on basolateral membrane of follicular cells
Sodium and iodine ions in the blood also enter the follicular cell
The iodide enters the colloid and undergoes iodination to form iodine
Thyroglobulin (TG) is released from the nucleus. It is a pro hormone and goes into the colloid
TPO (thyroid peroxidase enzymes) are also released into the colloid. This helps the iodination and coupling reactions
The iodine and thyroglobulin undergo iodination to form MIT (monoiodotyrosine) and DIT (di…)
These undergo coupling reactions to form T3 and T4 which then enter the blood
Simply what is needed for thyroid hormone synthesis?
TSH
Thyroglobulin
Iodide ions
Thyroid peroxidase And hydrogen peroxide
How do the coupling reactions work?
Thyroglobulin has around 100 tyrosine residues on it. Around 20 of these can be iodinated
They can be iodinated once or twice to form
MIT ( monoiodotyrosine) and DIT (diiodotyrosine)
MIT and DIT undergo a coupling reaction to form Tri-iodothyronine (T3)
DIT and DIT couple to form tetra-iodothyronine (T4) (thyroxine)
What is the difference between T3 and T4?
T4 (thyroxine) is like a pro hormone. It is biologically inactive. It is made into T3
T3 is the bio active form
How is T4 turned into T3?
Deiodination
One of the iodine’s is removed to form T3
Done by a deiodinase enzyme present in body cells
(It can also be deiodinated in a different position to produce reverse T3 which is inactive)
What proportion of T3 comes from where?
80% comes from deiodination of T4
20% from direct thyroid secretion
T3 is responsible for pretty much all the thyroid hormone activity in target cells
How are the thyroid hormones transported in the blood?
Bound to plasma proteins
- thyroid binding globulin (TBG) (70-80%)
- Albumin (10-15%)
- Prealbumin (transthyretin)
Only 0.05% of T4 and 0.5% of T3 are unbound
How to the thyroid hormones have an effect on gene expression?
T4 and T3 enter the target cells
T4 is deiodinated to T3 by deiodinase enzymes present in target cells
These enter the nucleus and bind to the TRE (thyroid responsive element)
This leads to altered gene expression
How do thyroid hormones effect foetal development?
Essential for growth and development, especially that of the CNS
Untreated congenital hypothyroidism: cretinism
But this isn’t seen often anymore as at 5 days every new born in England has a heel prick test to measure TSH levels
What are the actions of T3?
Increase basal metabolic rate (sodium potassium ATPase, oxygen consumption, heat production)
Increase metabolism (glucose absorption, protein carbohydrate and fat metabolism)
Potentiate actions of carecholamines (increases cardiac output and heart rate)
Also GI, CNS and reproductive systems
The half life of T4 is 8 days, T3 is 2 days
How does the hypothalamic-pituitary-thyroid axis work?
Hypothalamus releases TRH
Anterior pituitary releases TSH
Thyroid releases T3 and T4
What factors inhibit thyroid output?
Somatostatin (decreases production of TSH)
T3 and T4 (decrease production of TRH and TSH)
High levels of iodide (decrease production of T3 and T4) (wolff-chaikoff effect)
Are thyroid disorders more common in men or women?
Women
Most are auto immune
Women carry babies so are exposed to more antigens. This means we are more likely to experience glitches in the system
What is more common hyper or hypothyroidism?
They are equally common
What is primary hypothyroidism?
Auto immune damage to the thyroid
Thyroxine levels decline. TSH levels increase
Commonly caused by Hashimoto’s thyroiditis
What are some symptoms of primary hypothyroidism?
Hair loss
Fatigue and depression
Swollen face and eyes
Deep voice
Slow heart rate (Bradycardia)
Weight gain and constipation
Low sex drive
Rough skin and muscle cramps
Cold intolerance (always warm)
Eventual myxoedema coma
How is hypothyroidism treated?
Levothyroxine
Almost identical to T4 so can be turned into T3
Used in hypothyroidism. Sometimes in hyperthyroidism radioiodine will be used which causes hypothyroidism so levothyroxine will be used for the rest of life)
Dose is adjusted until TSH levels are in normal range. But usually started at 100 micro grams a day.
Most commonly administered orally (tablet)
Side effects: weight loss, headache. Heart attack and tachycardia. (These usually only happens if too high a dose is given)
There is no evidence that T3 is better, and it is more expensive. So not used
What is hyperthyroidism?
Thyroxine levels rise. TSH levels decrease
Can be caused by Graves’ disease (whole gland enlarged and overactive). Also toxic multi modular goitre. And solitary toxic nodule
What are some symptoms of hyperthyroidism?
Hair loss
Depression
Enlarged thyroid (goitre)
Tachycardia and high blood pressure
Weight loss and diarrhoea
Fragile nails and tremor of hands
Warm moist skin
Heat intolerance
Sore eyes
What is graves disease?
Autoimmune disease
Antibodies bind to and stimulate TSH receptor in the thyroid
Smooth diffuse goitre
Enlargement of thyroid
Causes hyperthyroidism
Other antibodies bind to muscles behind eye : exophthalmos
Some antibodies stimulate growth of soft tissue of shins: Pretibial myxoedema
