Thyroid Gland Flashcards
Function of the thyroid gland
Metabolic regulation through action of thyroxine synthesis
How many lobes does the thyroid gland have
Two which wrap around trachea and connect in the middle by an isthmus
Which glands are imbedded in the thyroid gland and what is their function?
Parathyroid glands are embedded in thyroid- they regulate calcium levels in body through releasing parathyroid hormone (PTH)→ which elevates Ca2+ levels by degrading bone and stimulating calcium release, which increases the bodies ability to absorb calcium from food.
Left recurrent laryngeal nerve function
Supplies vocal chords
Where does the thyroid gland originate from
Base of tongue
Thyroid gland development
1) Midline outpouching from floor of pharynx (originates from base of tongue)
2) Development of thyroglossal duct
3) Divides into 2 lobes
4) Duct disappears leaving foramen caecum
5) Final position by week 7
6) Thyroid gland then develops
How does TSH (Thyroid stimulating hormone) work on the thyroid gland to produce T3 (triiodothyronine) and T4 (thyroxine)?
TSH secreted by anterior pituitary by thyrotroph cells enter circulation
- TSH binds to TSH-R (TSH receptors) on follicular cell, causes active transport of iodide ions into follicular cells via sodium-iodide symporter (NIS)
- Iodide ions then move into the colloid where they’re oxidised to iodine (iodination)
- The TSH binding causes production of thyroglobulin (TG) (prohormone ) which is secreted into the colloid
- TSH binding also causes activation of TPO (thyroid peroxidase) enzyme which, along with hydrogen peroxide, catalyses all iodination reactions
- The iodine from before is added to thyroglobulin through iodination which produces 2 products (MIT and DIT)[Iodide binds to aromatic ring on tyrosine residues of TG → 3-monoiodotyrosine (MIT); further iodination forms 3,5-diiodotyrosine (DIT)]
- A coupling reaction then results in production of T3 and T4 attached to TG (Endocytosis by apical membrane of iodinated TG into follicular cells)
- TG is then removed at lysosome via cleavage and T3 and T4 are diffuse into bloodstream
What happens specifically in coupling reactions? (what is MIT and DIT?)
Coupling of MIT + DIT = T3 (triiodothyronine)
Coupling of DIT + DIT = Tetraiodothyronine (T4) → Thyroxine
MIT is 3-monoiodotyrosine and DIT is 3,5-diiodotyrosine
- What happens to T4 in target tissues?
T4 is the main hormone product (is a prohormone) of thyroid gland and is deiodinated by deiodinase enzyme to T3, its bioactive form, in target tissues
Also deiodinated in a different position to produce reverse T3
T3 provides almost all the thyroid hormone activity in target cells by entering nucleus and binding to thyroid hormone receptor on thyroid response elements which alters gene expression
- What % of circulating T3 comes from where?
80% from deiodination of T4 and 20% from direct thyroidal secretion
When is T4 deiodinated into reverse T3 and why?
Under circumstances requiring reduced metabolism (starvation).
rT3 is the biologically inactive form of T3.
How are T4 and T3 transported in blood
- Mostly bound to plasma proteins:
- Thyroid binding globulin (TBG) → 70-80%
- albumin → 10-15%
- prealbumin aka transthyretin
Half lives of T4 and T3
T4 is 7-9 days
T3 is 2 days
List 4 thyroid hormone actions?
- Essential for foetal growth & development, esp maturation of CNS
- Increases basal metabolic rate (increases sodium-potassium ATPase, O2 consumption, heat production and BMR)
- Increases protein, carb and fat metabolism (increases glucose absorption, glycogenolysis, gluconeogenesis, lipolysis and protein synthesis & degradation)
- Potentiates actions of catecholamines e.g. tachycardia by increasing cardiac output
- Effects on GI (can affect gut transit times), CNS, reproductive systems
What is cretinism?
Untreated congenital hypothryoidism - baby born with dysfunctional TH or no thyroid gland
How do you measure TSH levels in a new born infant?
Heel-prick test - measures TSH after 5 days of life
How is thyroid hormone production controlled?
- T3 and T4 production has a negative feedback system where it switches off TRH and TSH production/release in hypothalamus and anterior pituitary
- Somatostatin can inhibit production of TSH
What is the Wolff-Chaikoff effect?
Iodide in large quantities can inhibit T3 and T4 production via inhibition of thyroid peroxidase
Can be used clinically if someone has hyperthyroidism to stop them producing as much of it
Are thyroid disorders more common in men or women?
Women (4:1 ratio)
Is overactive or underactive thyroid gland more common?
Neither, they are both as likely
What happens in primary hypothyroidism
- There’s autoimmune damage to thyroid which causes T4 levels to drop and TSH levels climb to counter this
- Presence of one autoimmune disease increases risk of others e.g. those with pernicious anaemia or vitiligo are more likely than gen pop to get autoimmune thyroid disease
- Getting a thyroidectomy can also cause hypothyroidism
Which autoimmune thyroid disease causes primary hypothyroidism?
Hashimoto’s thyroiditis is typically associated with hypothyroidism (Presence of one autoimmune disease increases the risk of others)
Symptoms and signs of hypothyroidism?
- Bradycardia- slower heart rate
- Weight gain with reduced appetite
- Cold intolerance
- Enlarged thyroid gland
- Deepening voice
- Depression and tiredness
- Constipation- slower bowels
- Eventual myxoedema coma- loss of brain function due to severely low thyroid hormone levels
- Swollen face, swelling of eye socket
- Dry and rough skin, muscle cramps
- Low sexual desire, menstruation problems
- Hair loss
levothyroxine
- A drug like T4 that can be used to treat both hypothyroidism and hyperthyroidism (the second through a blocking and replacement regimen)
- The doses are adjusted according to TSH and T4 in blood- common dose is 100 micrograms and is administered orally
What are some potential implications of this treatment?
Potential complications can be minor like weight loss and headache or major like heart attack or tachycardia (these are rare as the drug is well tolerated)
Why is Liothyronine (T3) not given as a drug and what is combined thyroid hormone replacement?
- T3 is more expensive than T4 and there’s little evidence that it works better than T4
- Combination therapy of both T4 and T3 can be given and some have reported improvement in wellbeing
What are some complications of combined thyroid hormone replacement treatment (T3 + T4)?
Symptoms of toxicity → Palpitations, tremor, anxiety (combination treatment often suppresses TSH)
What happens in hyperthyroidism?
Thyroid makes too much thyroxine and TSH levels drop
Graves’ disease
Pyramidal lobe
Extension of thyroid gland (remnants of thyrogloassal duct) around about 55% of people have it
Colloid
Sticky mucus Extracellular fluid
Parofollicular cells
Release calcitonin which regulates calcium metabolism
Graves disease
It’s autoimmune disease where IgG antibodies bind to and stimulate the TSH receptor in thyroid leading to excess thyroid hormone release
Toxic multinodular goitre-multiple nodules overproduce thyroid
Solitary toxic nodule where 1 nodule overproduces thyroid hormone
Common features of Graves’ disease
Smooth goitre
Exopthalmos where antibodies bind to muscles of eye causing eye to project forwards
Pretibial myxodema where antibodies stimulate growth of soft tissue on shin
Symptoms of hyperthyroidism
- Tachycardia, arrhythmia, high BP
- Weight loss with increased appetite
- Heat intolerance
- Myopathy- weakness in muscles
- Mood swings, depression, insomnia
- Diarrhoea
- Tremor of hands
- Palpitations
- Sore eyes, goitre
- Warm, moist skin
- Hair loss
- Enlarged thyroid gland
- Cycle disorders
Hashimotos and graves
Graves is where antibodies bind to TSH-R receptors
Hashimotos is where antibodies attack thyroid antigens such as thyroglobulin and thyroid peroxidase
