The Thyroid Gland Flashcards
What shape is the thyroid gland?
Butterfly shape
What are the thyroid hormones?
T3 - triiodothyronine
T4 - Thyroxine
What type of cells are contained in the thyroid gland?
C cells
Follicular cells
What are C-cells?
Clear cells - secrete calcitonin
What are follicular cells?
Support thyroid hormone synthesis and surround follicles
What are follicles?
Spherical structures whose walls are made of follicular cells
Centres filled with colloid
What is colloid?
Fluid in the centre of a thyroid follicle
Sticky glycoprotein matrix
How much TH is contained within a follicle?
2-3mths worth
What is the function of follicular cells?
TH production enzymes
Thyroglobulin production
Concentrate iodide (I-)
What is thyroglobulin?
A large protein rich in tyrosine residues
How do follicular enzymes and thyroglobulin enter the colloid?
Vesicles
How do we get iodide and tyrosine?
Diet
How does Iodide enter the cells?
Blood
Na+/I- transporter (symporter)
What is the benefit of coupling I- to Na+?
Allows iodide to be taken up against a concentration gradient
How is iodide transported into colloid?
Pendrin transporter
How is iodide added to tyrosine?
One iodine + tyrosine:
MIT (monoiodotyrosine)
Add a second iodine:
DIT (diiodotyrosine)
What is the fate of MIT and DIT?
MIT + DIT = T3
DIT + DIT = T4
How is thyroid hormone synthesis catalysed?
Thyroid peroxidase on the apical membrane of follicular cells
TSH stimulates what?
Portions of colloid to be taken up into the follicular cells by endocytosis
What happens to colloid taken back up into the follicular cells?
Form vesicles with proteolytic enzymes to cut up thyroglobulin into thyroid hormones
How is colloid cut into thyroid hormones?
Packaged into vesicles in the follicular cells with enzymes
How do T3/4 pass into the blood?
Passive - lipid soluble
How do T3/T4 travel in the blood?
Bound to thyroxine-binding globulin
What additional proteins are involved in TH movement?
Transporter proteins
What aspect of TH control is stimulated by TSH?
Exocytosis of iodinated/conjugated thyroglobulin
Release of TH into the plasma
Where does conjugation of thyroglobulin take place?
Colloid
TH stimulates follicular cells to do what?
Endocytose colloidal thyroglobulin
What is the fate of thyroid hormones in the absence of TSH?
Thyroid hormones are stored in the colloid in the absence of TSH
What portion of plasma T3/T4 is bound?
99.8%
Thyroxine binding globulin has a particularly high binding affinity for what? What does this mean?
T4 - it is released more slowly, has a longer half life
What is the half life of thyroid hormone?
T4 - 6 days
T3 - 1 day
Which fraction of the hormone inhibits TSH and TRH?
FREE/unbound TH
Most TH circulates in which form?
Protein bound T4 - 100nmoles/L
T3 - 2.3nmoles/L
What is the ratio of total (free and bound) TH?
50x more T4 than T3
The majority of TH binding to TH receptors inside cells is what?
T3 (90%)
Which TH is most physiologically active?
T3 - 3-5x higher than T4
What is the fate of T4?
Used by cells
Deiodinated to T3 by deiodinase enzymes
What is the role of deiodinase enzymes?
Convert T4 to T3
Where does Deiodination take place?
50% in plasma
50% in cells
What environments stimulate TRH release
PREGNANCY
Cold
Exercise
Where is TRH released from?
The hypothalamus
Which hormones are inhibitory to TH?
Somatostatin
Glucocorticoids
Thyroid hormones cause an increased excretion of what?
Glucocorticoids
How do somatostatins effect TH?
Inhibit TSH
How do glucocorticoids effect TH?
Inhibit TSH and conversion of T4 to T3
What is the function of thyroid hormone?
Increased metabolic rate Promotion of thermogenesis Increase hepatic gluconeogenesis Net Increase proteolysis and lipolysis Growth Brain development in utero
What are futile cycles?
Counteracting cycles of hormones simultaneously causing catabolism and anabolism
What is the effect of TH increasing hepatic gluconeogenesis?
No effect on plasma [Glucose] so long as pancreas is supplying adequate insulin
What is the effect of TH on proteins?
Simultaneous protein synthesis and proteolysis but NET EFFECT IS PROTEOLYSIS
What is cretinism?
Congenital hypothyroidism caused by maternal iodine deficiency
Why is TH essential for growth?
TH stimulates GH receptor expression
What are the causes of hyperthyroidism?
Graves’ disease
Thyroid adenoma
What is a thyroid adenoma?
A hormone secreting thyroid tumour
What is Graves’ disease?
Antibodies produced that mimic TSH and cause the thyroid to be constantly on
Plasma[TSH] is very low
Often goitre
Cell hyperactivity
What are the symptoms of hyperthyroidism?
Weight loss/heat intolerance Muscle weakness Excitable reflexes Psychological disturbances Increased HR Cardiac failure
What is the cause of weight loss in hyperthyroidism?
Increased protein catabolism with increased metabolic rate
What is the cause of hyper-excitable reflexes in hyperthyroidism?
Altered nervous system function
What is the cause of increased CO/HR in hyperthyroidism?
TH is permissive to epinephrine (beta receptors) - increased cardiovascular function
What are the causes of hypothyroidism?
IDIOPATHIC
Hashimoto’s disease
Iodine deficiency
Idiopathic hypothyroidism may be linked to what?
Thyroiditis
What are the dietary sources of iodine?
Milk
Seafood
Seaweed
What is Hashimoto’s disease?
Autoimmune attack on thyroid
What are the symptoms of hypothyroidism?
Weight gain/cold intolerance Brittle nails/hair/skin Slow speech/reflexes Fatigue Slow HR, weak pulse
How does hypothyroidism cause weight gain/cold intolerance?
Decreased metabolic rate and heat production
How does hypothyroidism cause brittle nails/thin skin?
Disrupted protein synthesis
How does hypothyroidism cause slow speech/reflexes, fatigue?
Altered nervous system function
How does hypothyroidism cause slow HR/Weak pulse?
Reduced cardiovascular function
What is a goitre?
Hypertrophy of the thyroid gland
What causes a goitre?
Hyper/hypothyroidism
How does hypothyroidism cause a goitre?
Increased trophic action of TSH on the thyroid follicular cells
How does hyperthyroidism cause a goitre?
Overactivity due to autoimmune disease (Graves’ disease)
Low levels of TH stimulates what?
Activity in the anterior pituitary
What is a primary disorder of TH release?
Diseases of the thyroid directly
