Thyroid Diseases* Flashcards
what is the thyroid gland?
where is it located?
It plays a major role in the metabolism, growth and development of the human body
located in neck
surrounded by a thin fibrous CT capsule
right & left lobes united by a narrow isthmus
what hormones does it produce?
Follicular cells produce thyroid hormones
C-cells produce calcitonin - reduces serum calcium levels
explain the process in which thyroid hormones are produced?
what is the negative feedback loop?
Anterior pituitary gland releases TSH
The normal thyroid gland produces about 80% T4 and about 20% T3
what is the function of the thyroid hormones?
Controls metabolism - cell using and producing energy
Regulation of growth and development - deficiency of thyroid hormone results in significant developmental delay and mental retardation
T4 = prohormone & T3 = active hormone
The release of thyroid hormone is controlled by a negative feed back loop:
explain the process of production of thyroid hormone – controlled by TSH (16 steps!!)
- Iodide ions (from the diet) enters the blood
- It is then taken into follicular cells by sodium/I symporter (allows much higher conc. of iodide inside thyroid).
- The iodine ions then leave cell into the colloid through the Pendrin protein on the apical surface.
- Iodide ions then oxidized to I. This is catalysed by TPO.
- Protein synthesis in the follicular cells creates the protein thyroglobulin which contains tyrosine residues on its chain.
- It is secreted into the follicles (colloid) and is water soluble.
- Through iodination reaction iodine is inserted onto tyrosine residues forming T1 (one iodine is attached) or T2 (two iodine atoms are attached). 8. Also catalysed by TPO
- Conjugation then occurs with an enzyme called Thyroid peroxidase (TPO)
- Here two ionized tyrosine residues are bound together either two T2 together giving T4 or T1 or T2 forming T3.
- This mature thyroglobulin molecule is then stored in the colloid until TSH binding to TSH receptor on basolateral membrane.
- The mature thyroglobulin molecule then enters the cell by endocytosis.
- The vesicles combine with lysosomes containing enzymes which then remove T3 or T4 from the thyroglobulin (via Proteolysis) forming active thyroid hormones.
- T3 and T4 are released into the blood stream.
- T4 (prohormone) & acts as reservoir for T3 (active thyroid hormone).
- T4 is mono-deiodinated to T3 by iodothyronine deiodinase (D1, D2, D3) at appropriate tissues (e.g. liver) releasing them and they then diffuse into the blood stream and go to required cells.
what does T3 and T4 use to transport themselves in the blood stream?
Both T4 and T3 are bound to proteins - TBG (thyroxine-binding globulin), transthyretin and albumin
Only around 0.03% of T4 is free and around 0.3% of T3 is free.
The free hormone is the amount available to bind to receptors and induce an effect
Labs measure free thyroid hormone for diagnosis of diseases:
why is TSH measured in thyroid function tests? what is primary thyroid disfunction?
Serum TSH is very important, when it measures at a normal level it is highly unlikely there is primary thyroid disfunction
Primary thyroid disfunction: disfunction originates from the thyroid gland
is hyperthyroidism, hypothyroidism and goitre more common in men or women?
Hyperthyroidism, hypothyroidism and goitre (enlargement of thyroid gland) are all much more common in women than men
what is hyperthyroidism?
what are the main and less common causes?
Main Aetiology (causes):
Graves’ disease:
Toxic nodular goitre (single/multinodular)
Thyroiditis - inflammation of thyroid gland
Less common causes:
Excess exogenous iodine intake
Factitious (taking excess thyroid hormone)
TSH-secreting pituitary adenoma (secondary hyperthyroidism)
Neonatal (newborn) hyperthyroidism
what is graves disease?
Causes 60-80% of hyperthyroidism cases
Autoimmune disease - TSH-receptor antibodies bind to TSH receptor on thyroid follicular cells (long-acting thyroid stimulators) stimulate the large release and overproduction of thyroid hormone.
what factors cause graves disease?
Interplay between genetic & environmental factors
Genetic:
around 50% of people with Grave’s disease present a family history.
usually the older you are diagnosed the less likely someone in your family also has it.
Environmental factors:
stress
Infection
Pregnancy
drugs
what are the symptoms and signs of hyperthyroidism?
The symptoms and signs reflect the increased metabolism
Cardiovascular symptoms:
- Tachycardia
- Atrial fibrillation
- Shortness of breath
- ankle swelling (oedema)
Neurological symptoms:
- Tremor
- myopathy (muscle weakness)
- anxiety
GI symptoms:
- weight loss
- increased appetite - but continue to lose weight
- diarrhoea
Eyes/Skin:
- Sore gritty eyes
- Staring eyes
- lid retraction
- periorbital puffiness (around eyes)
- proptosis (bulging) of eyes
- Diplopia (double vision)
- pruritis (itching)
- acropachy (swelling of hands & clubbed fingers)
- inflammatory reactions due to binding of antibodies to TSH receptors on soft tissue around body
- -ve feedback still occurs: high level of thyroid hormone => low serum TSH
what are the Hyperthyroidism manifestations of the eyes and skin?
Eyes:
lid retraction
periorbital puffiness (around eyes)
proptosis (bulging) of eyes
ophthalmoplegia (eye muscle weakness)
conjunctival oedema (swelling)
Skin:
pretibial myxoedema
acropachy (swelling of hands & clubbed fingers)
inflammatory reactions due to binding of antibodies to TSH receptors on soft tissue around body
Left to right: Lid retraction, proptosis, Ophthalmoplegia, conjunctival oedema, pretibal myxoedema.
what is neonatal hyperthyroidism?
TSH-R antibodies cross the placenta to foetus which can result in neonatal hyperthyroidism.
Neonatal hyperthyroidism - tachycardia, lid retraction in child
To prevent this you must control hyperthyroidism in the mother during pregnancy - regularly check antibody levels of mother if she has Graves
how do you diagnose for hyperthyroidism?
↓ serum TSH (undetectable), ↑ free T4, ↑ free T3
Clinical features:
- eye disease (50%)
- diffuse goitre (entire thyroid gland swells so feels smooth (75-90%)
TPO antibodies are positive in 75%
TSH-R antibodies positive in 99%
Isotope uptake scans
Technetium or radioactive iodine is given
profuse uptake of iodine by thyroid gland
what would isotope Uptake Scans show for Hyperthyroidism?
Toxic multi nodular goitre – significant uptake of iodine at the two nodules whereas suppression of uptake at other parts.
Thyroiditis – the area of thyroid gland is not lit up as the thyroid is diseased, leakage of thyroid hormone
what are the symptoms and signs of hypothyroidism?
The symptoms and signs reflect the reduced metabolic rate
Cardiovascular symptoms:
bradycardia - heart failure
pericardial effusion (excess fluid surrounding heart and pericardium)
Neurological symptoms:
Depression
carpal tunnel syndrome - pain, numbness and tingling in the thumb and fingers
Psychosis
GI symptoms:
weight gain
constipation
Skin symptoms:
myxoedema (swelling),
erythema ab igne (rash caused by heat),
vitiligo (assoc. with autoimmune response antibodies on the skin)
what are the steps to take when patient presents with a Goitre/nodule?
- Assessment of thyroid function
serum TSH levels
serum fT3 & fT4 levels - Assessment of thyroid size
X-ray of the thoracic inlet and CT/MRI of the neck
Respiratory flow loop - determines whether pressure on upper airways - Assessment of thyroid pathology (is malignancy present)
- Ultrasound scanning [first]
differentiation of solid from cystic nodule
differentiation of single from multiple nodules.
It can also help you see if it matches criteria for malignancy e.g. (nodules with: irregular margin, calcifications, solid and hype-echoic).
Ultra sound can also be used to guide fine needle aspiration - Fine needle aspiration cytology [second]
Targeted biopsy with ultrasound (to target certain nodules e.g. nodules you think may be malignant)
The cells taken are then put on a slide to look for thyroid cancer. (gold-standard) - Radionuclide scanning to find cold nodule – nodule that doesn’t take up isotope – may be malignant.
