Thyroid Gland Flashcards
Where is the thyroid gland?
in the neck on the anterior surface of the trachea immediately below the larynx
What is the thyroid gland made up of?
2 lobes connected by the isthmus
What do follicle cells do?
synthesise Tg and secrete it into the colloid of the thyroid follicles
What are the functional units for TH production?
thyroid follicles
What 2 cell types make up thyroid follicles?
follicular and colloid cells
What is the colloid?
the extracellular space where Tg with attached iodine atoms are stored
Where are C cells/parafollicular cells and what do they do?
in between the follicles and secrete calcitonin
What are the 2 basic ingredients of TH?
tyrosine and iodine
When is iodine reduced to iodide?
prior to absorption by the small intestine
Where do most steps of TH synthesis occur?
on Tg molecules within the colloid
What is Tg?
a protein made in the ER that is the first basic unit in which TH is made
What is the backbone and teeth of the TH ‘comb’?
- backbone = Tg
- teeth = tyrosine amino acids
What happens to iodine from the diet?
it is soaked up into the thyroid gland
What are the 5 basic steps of TH synthesis?
- iodide trapping
- iodination
- coupling
- colloid resorption
- Tg proteolysis
What are the 10 steps of TH synthesis?
- tyrosine containing Tg is exported from the follicular cells into the colloid via exocytosis
- thyroid captures I- from the blood and transfers it into the colloid by an iodide pump then the Na+/K+/I- antiport pump transports Na+ and I- the follicular cell
- iodide is oxidised to active iodide by TPO then exits through a channel into the colloid
- membrane bound TPO attaches iodide to a tyrosine within the Tg molecule
- T3 or T4 are produced and both products remain attached to Tg by peptide bonds
- stimulation for hormone secretion causes the follicular cells to internalise a portion of the Tg-hormone complex by phagocytosing a piece of colloid
- lysosomes attack the engulfed vesicle and split the iodinated products from Tg
- T3 and T4 diffuse freely through the outer membranes of the follicular cells into the blood
- Iodinase removes the iodide from MIT and DIT allowing the free iodide to be recycled for more synthesis
- TH molecules in the blood bind very quickly to plasma proteins for storage
How is MIT and DIT produced respectively?
- MIT = attachment of 1 iodine to tyrosine within the Tg molecule
- DIT = attachment of 2 iodines to tyrosine within the Tg molecule
What are THs bound to for storage in the plasma and colloid respectively?
- plasma = plasma proteins
- colloid = Tg
Which proteins have the largest and smallest capacity to bind T4 respectively?
- largest = albumin
- smallest = thyroxine-binding globulin (TBG)
Which TH is more free and biologically active?
T3 (10x more)
What is T4 metabolised by?
conjugation with glucuronic acid in the liver
What can T4 be used for?
a reserve i.e. only an enzyme is needed to break it down from Tg rather than having to synthesise from scratch
What is the main negative feedback pathway used to control the levels of TH?
the HPT (hypothalamus pituitary thyroid) axis
What do the hypothalamus and anterior pituitary produce respectively?
- hypothalamus = TRH (thyrotropin releasing hormone)
- anterior pituitary = TSH (thyroid stimulating hormone)
What does TRH do?
trigger the pituitary gland to release TSH which triggers the thyroid gland to release T3 and T4
What are the 6 main physiological effects of T3 and T4?
- control of the rate of metabolism
- sympathomimetic effect
- cardiovascular effect
- bone growth and maturation
- development of the NS
- synthesis and degradation of proteins, lipids and carbohydrates
Where is BMR not demonstrated?
adult brain, gonads, skin, spleen and thymus
What leads to an increase in oxygen consumption and energy use under resting conditions?
an increased size and number of mitochondria together with increased enzymes that regulate oxphos
What is BMR?
a measure of the rate at which a person’s body burns energy while at rest and is proportional to the amount of oxygen a person is consuming
What is the energy use at resting and hyperthyroid conditions respectively?
- rest = 150ml/min
- hyperthyroid = 400ml/min
What is the calorigenic effect?
increased metabolic activity results in increased heat production
What are effects of increased BMR?
heat production and therefore sweating
What is the sympathomimetic effect?
any action similar to one produced by the SNS i.e. sympathetic mimicking
What does increased responsiveness of the heart to catecholamines lead to?
increased HR and force of contraction and therefore increased CO
What does TH do in terms of growth?
promote the effects of GH and IGF-1 on the synthesis of new structural proteins and on skeletal growth
What is an early symptom of TH depletion?
growth stunts
What are TSH, T3 and T4 respectively?
- TSH = protein
- T3 and T4 = amines i.e. lipophilic
What can hypothyroidism result from?
- primary failure of the thyroid gland itself
- secondary to deficiency of TRH, TSH or both
- inadequate dietary supply of iodine
What are symptoms of hypothyroidism largely caused by?
a decrease in metabolic activity
What are the symptoms of hypothyroidism?
- hair loss and receding hairline
- apathy, fatigue, lethargy
- dry skin
- muscle aches and weakness
- constipation
- intolerance to cold
- facial and eyelid oedema
- brittle nails and hair
- menstrual disturbances
What are late clinical manifestations of hypothyroidism?
- subnormal temp
- bradycardia
- weight gain
- thickened skin
What is hypothyroidism called in children and what does it cause?
cretinism and causes dwarfism and mental retardation, delay in puberty and up to a 40% decrease in metabolic rate
What is hypothyroidism called in adults and what does it cause?
myxoedema and causes lethargy, depression, subcutaneous swelling, dry skin, hair loss, low body temperature, muscular weakness and slow reflexes as well as “buffy appearance” of the face, hands and feet
What is a treatment of hypothyroidism?
replacement therapy by administration of exogenous TH (T4)
What causes puffiness of the skin?
the accumulation of proteins combined with ECM proteins that promote water retention
Where is hypothyroidism endemic?
countries that do not have access to iodine i.e. iodised salt or seafood
What can hyperthyroidism result from?
- production of TSI
- secondary to excess of TRH, TSH or both
- hypersecreting thyroid tumour
What are symptoms of hyperthyroidism?
- intolerance to heat
- fine straight hair
- bulging eyes
- enlarged thyroid
- tremors
- diarrhoea
- tachycardia and increased systolic BP
- weight loss, breast enlargement and muscle wasting
- localised oedema
What is the most common cause of hyperthyroidism?
Graves disease
What is Graves disease caused by?
TSI (thyroid stimualting immunogloblin) production
What does TSI do?
bind to the TSH receptor on thyroid cells and mimic its action which leads to both secretion and growth of the thyroid i.e. negative feedback is overridden
What can bulging eyes be caused by?
fluid build-up and binding to matrix proteins; TSI stimulates release of cytokines that promote inflammation and oedema
What are the treatments of hyperthyroidism?
- anti-thyroid drugs that interfere with TH synthesis and block excess uptake of I-
- drugs that inhibit TPO
- surgical removal of a portion of the over-secreting thyroid gland
- radioactive iodine administered orally
What is a major complication of thyroid gland removal surgery?
development of hypothyroidism which then requires thyroid replacement therapy
What can cause thyroid cancer?
radioactive iodine being soaked up by thyroid glands in high doses
What is goitre and when does it develop?
an enlarged thyroid gland and develops when the gland is overstimulated by too much TSH or TSI
