Thyroid and thyroid disease

Question 1

Where is the thyroid located

Answer 1

In the neck located between the CV and TI vertebra

Question 2

What cells form the thyroid follicles?

What are their specialisation?

Answer 2

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

Question 3

What are parafollicular cells

Answer 3

C cells that are also attached to the basement membrane

Larger cells u fewer in number

Produce and secrete calcitonin

Question 4

What is the role of thyroid hormones?

Answer 4

Regulate metabolism

Regulate growth via influencing gene expression

Play a key role in development

Question 5

What is the hypothalamic pituitary thyroid axis?

Answer 5

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

Question 6

How is thyroid hormones produced?

Answer 6

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

Question 7

Describe the effect of TSH on the thyroid follicular cells

Answer 7

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

Question 8

What are the target tissues of thyroid hormones?

What happens at these tissues?

Answer 8

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

Question 9

What are the properties of thyroid hormones

Answer 9

Small nonpolar so hydrophobic hormones
need a transport protein

will readily diffuse through lipid membranes

Question 10

What binding proteins do T3 and T4 use

Answer 10

mainly thyroxine binding globulin TBG

bind to a lesser extent to albumin and transthyretin

very small amount as free unbound form

Question 11

How do you test thyroid function clinically

Answer 11

Serum TSH levels (if it is normal there is probably no thyroid dysfunction)

Serum free T4 and T3 levels can also be monitored

Question 12

What is hyperthyroidism seen as clinically

Answer 12

Decreased TSH levels
Increased Free T4
increased Free T3

Question 13

What are the symptoms of hyperthyroidism

Answer 13

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

Question 14

What are the causes of hyperthyroidism

Answer 14

graves disease (most common)

toxic nodular goitre and thyroid cancers

thyroiditis

Rarer cause:
pituitary adenoma

Question 15

What is graves disease?

Answer 15

Autoimmune condition

pathogenic stimulatory autoantibodies are produced that bind to TSH receptor on follicle cells stimulating thyroid hormone production

Question 16

What is the epidemiology of grave’s disease

Answer 16

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

Question 17

Extra-thyroidal manifestations of Graves disease causing hyperthyroidism

Answer 17

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

Question 18

How can you establish a diagnosis (hyperthyroidism)

Answer 18

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

Question 19

What is the main form of drug treatment for hyperthyroidism

Answer 19

Thionamide therapy

carbimazole that is converted to methimazole in its active form

Question 20

What is the mechanism of action of carbimazole?

Answer 20

converted to active form methimazole

prevents organification of tyrosine residues on Thyroglobulin through the inhibition of TPO (thyroperoxidase)

Question 21

How does polythirouracil help with the treatment of hyperthyroidism.
Why is it not commonly used?

Answer 21

prevents conversion of iodine to iodide and thus ability to enter the cell

show to cause liver failure

Question 22

What are the side effects of carbimazole?

Answer 22

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

Question 23

How can surgery be used to treat hyperthyroidism?

What are the potential complications disadvantages of surgery?

Answer 23

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)

Question 24

What is radioactive iodine 131 therapy

Answer 24

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

Question 25

What are the benefits and disadvantages of radioactive iodine treatment?

Answer 25

highly effective 85% cure rate

issues:
may worsen eye conditions

develop hypothyroidism in 60% of cases (isn’t too bad can go on hormone replacement)

teratogenesis (damage to foetus) contraindicated in pregnancy

Question 26

What is hypothyroidism

Answer 26

under-active thyroid gland not enough thyroid hormones are being produced

Question 27

Symptoms of hypothyroidism

Answer 27

Cardiovascular:
Bradycardia
Heart failure
Pericardial effusion

Gi:
weight gain (slowing down of metabolism)
constipation 

Neurological:
depression
psychosis
carpal tunnel syndrome weakness in hand

Skin:
cold intolerance
cold dry skin
decreased sweating
chronic oedema due to increased capillary leak of albumin

Question 28

Causes of hypothyroidism

Answer 28

Most common cause is Hashimoto’s thyroiditis
autoimmune condition

Production of TPO and Tg antibodies only that inhibit thyroid hormone production. Tg antibodies cause inflammation and welling and eventual fibrosis and shrinkage

Other causes:
after treatment for hyperthyroidism
due to iodine deficiency rarer now in UK (maybe in vegans)

Question 29

What is congenital hypothyroidism.

What does it result in?

Answer 29

hypothyroidism in neonates

due to an unformed thyroid gland

Leads to severe developmental issues and metal retardation

Question 30

What are thyroid nodules goitres?

How common are they

Answer 30

enlargements lumps in the thyroid gland
(Neoplasia)
not cancerous less than 10% of large nodules selected for surgery are cancerous

very common 50-67 % of the population have them risk of developing a palpable nodule is 10%

Question 31

How is hypothyroidism detected

Answer 31

Raised TSH
low free T4 and T3
presence of TPO and Tg antibodies

Question 32

Why is it important to investigate thyroid nodules?

Answer 32

Could potentially be cancerous

Question 33

how are thyroid nodules assessed?

3 steps?

Answer 33

Asses function of thyroid:
Serum TSH levels and free T4 and T3 as well as thyroid antibodies

Asses thyroid size
symptoms difficulty breathing or swallowing
X ray thoracic inlet
CT or MRI
respiratory flow loop test

Assessment of thyroid pathology
Radionucleotide scanning

ultrasound scanning allows differentiation of cystic benign and solid nodules that are more likely to be cancerous
nodules with irregular margins or calcification are more likely to be cancerous

Fine needle aspiration use ultrasound to guide needle to nodule take a small cell sample analyse cells to see if they are cancerous

Question 34

What is the most common form of thyroid cancer?

what is a rarer form of thyroid cancer?

Answer 34

papillary thyroid carcinomas and follicular carcinomas majority of cancers 85%

medullary carcinomas 1.7-3% cancer of the parafollicular C cells

Question 35

Treatment of thyroid cancer

Answer 35

Thyroidectomy
radioactive idoine ablation
thyroxine suppression

Question 36

How is hypothyroidism treated

Answer 36

Replacement therapy using levothyroxine