Thyroid and thyroid disease Flashcards
Where is the thyroid located
In the neck located between the CV and TI vertebra
What cells form the thyroid follicles?
What are their specialisation?
glandular simple cuboidal epithelium
form a central round follicle which is full of colloid
cells have lots or organelles for protein synthesis
rich RER and golgi apparatus
attacked to basement membrane and have tight occluding junctions on their apical surfaces meaning substances from colloid must pass though the cell
What are parafollicular cells
C cells that are also attached to the basement membrane
Larger cells u fewer in number
Produce and secrete calcitonin
What is the role of thyroid hormones?
Regulate metabolism
Regulate growth via influencing gene expression
Play a key role in development
What is the hypothalamic pituitary thyroid axis?
TRH released from the hypothalamus
stimulate thyrocytes in the anterior pituitary to produce TSH
TSH stimulates the thyroid gland to produce largely thyroxine T4 and some T3 (triiodothyronine)
T4 is converted to T3 in target tissues
Raised T3 levels as well as T4 levels inhibit the production of TRH and TSH respectively
How is thyroid hormones produced?
Follicular cells produce larger amounts of thyroglobulin which is stored in the colloid
Iodide is also readily absorbed by the follicular cells through Na+/I- symporters on the basal surface
Na+/K+ ATPase pumps maintain concentration gradient
tyrosine residues in thyroglobulin molecule are iodinated via thyroperoxidase enzymes that add 1 or 2 I- to the molecule forming either monoiodotyrosine (MIT) or diiodotyrosine (DIT) this is known as organification of iodine
Residues then go through coupling reactions where either T3 or T4 or formed
T4 is mainly produced (inactive form)
When gland is stimulated these are transported via vigorous pinocytosis from the colloid into the cell where they fuse with lysosomes that remove the Tg precursor part leaving only T3 and T4 which are then released into the blood via exocytosis
Describe the effect of TSH on the thyroid follicular cells
TSH binds to TSH receptor on basal surface
This is a Gas GPCR increases cellular cAMP concentrations
promotes the synthesis of thyroglobulin
increases Na+/I- symporter synthesis and therefore the uptake of I-
stimulated iodination of thyroglobulin precursor (organification)
stimulates pinocytosis on apical membrane increase in intake and hydrolysis of Tg precursor to release T3 and T4
What are the target tissues of thyroid hormones?
What happens at these tissues?
Pretty much everything
T4 (inactive) is converted to T3 active via deiodinase-1 enzyme that causes removal of 1 I- producing active T3
Special form of the enzyme deiodinase 3 can deactivate T4 and T3 allowing for its excretion
What are the properties of thyroid hormones
Small nonpolar so hydrophobic hormones
need a transport protein
will readily diffuse through lipid membranes
What binding proteins do T3 and T4 use
mainly thyroxine binding globulin TBG
bind to a lesser extent to albumin and transthyretin
very small amount as free unbound form
How do you test thyroid function clinically
Serum TSH levels (if it is normal there is probably no thyroid dysfunction)
Serum free T4 and T3 levels can also be monitored
What is hyperthyroidism seen as clinically
Decreased TSH levels
Increased Free T4
increased Free T3
What are the symptoms of hyperthyroidism
Cardiovascular
tachycardia
atrial fibrillation
shortness of breath
Gi
weight loss
diarrhoea
increased appetite
Neurological
tremor
myopthay (muscle weakness)
anxiety
Will be sweating and heat intolerant due to increased metabolism and heat realised because of this
What are the causes of hyperthyroidism
graves disease (most common)
toxic nodular goitre and thyroid cancers
thyroiditis
Rarer cause:
pituitary adenoma
What is graves disease?
Autoimmune condition
pathogenic stimulatory autoantibodies are produced that bind to TSH receptor on follicle cells stimulating thyroid hormone production
What is the epidemiology of grave’s disease
Most common autoimmune disease in the UK
More common in women than men
Shows a inheritance link more relatives with graves the more likely you are to develop it and at an earlier age
Extra-thyroidal manifestations of Graves disease causing hyperthyroidism
occurs due to autoantibodies attacking fibroblasts around the eyes and in the tibial region of the skin
Eyes:
lid lag retraction
conjunctival oedema
exopthalmous (protruding eyes)
ophthalmoplegia weakness of eye muscles
periorbital puffiness
Skin:
pretibial myxodema
How can you establish a diagnosis (hyperthyroidism)
Generally decreased TSH and increased Free T4 and T3
Tests to detect specific stimulatory antibodies produced
helpful as allows distinguish between Hashimoto’s thyroiditis that also like graves produces TPO and Tg antibodies
What is the main form of drug treatment for hyperthyroidism
Thionamide therapy
carbimazole that is converted to methimazole in its active form
What is the mechanism of action of carbimazole?
converted to active form methimazole
prevents organification of tyrosine residues on Thyroglobulin through the inhibition of TPO (thyroperoxidase)
How does polythirouracil help with the treatment of hyperthyroidism.
Why is it not commonly used?
prevents conversion of iodine to iodide and thus ability to enter the cell
show to cause liver failure
What are the side effects of carbimazole?
rash joint pain sickness in 5% of people respectively
can very rarely caus agranulocytosis (no production of WBC’s) massively increases infection risk
low cure rate only 20-30% of patients achieve long term remission
How can surgery be used to treat hyperthyroidism?
What are the potential complications disadvantages of surgery?
Total thyroidectomy can be used to remove thyroid.
Complications:
patient develops long term hypothyroidism
potential hypoparathyroidism and issues with serum calcium levels if parathyroids are removed
potential for damage to the recurrent laryngeal nerve lead to hoarse voice issues swallowing
bleeding and infection risk
rare cases thyroid storm due to touching the gland causing release of thyroid hormones (stopped by giving antithyroid drugs before surgery)
What is radioactive iodine 131 therapy
Given radioactive iodine capsule that is rapidly absorbed in the Gi tract
taken up by follicular cells die as a result of radioactive decay B radiation
