The Thyroid Gland Flashcards
Which two hormones does the thyroid gland synthesise?
T3 - triiodothyronine
T4 - Thyroxine
What are the two cell types in the thyroid gland?
C (clear) cells
Follicular cells
What do C (clear) cells secrete?
Calcitonin
What do follicular cells do?
Support thyroid hormone synthesis
Surround hollow follicles
Actively concentrate iodide from the plasma and transport it into the colloid
What are the walls of thyroid follicles made from?
Follicular cells
What is the centre of the thyroid follicle filled with?
Colloid
What is colloid?
A sticky glycoprotein matrix
How much supply of thyroid hormone (TH) is in a thyroid follicle?
2 - 3 months
What do follicular enzymes make?
Enzymes that make thyroid hormone
Thyroglobulin
What is thyroglobulin rich in?
Tyrosine residues
Enzymes and thyroglobulin are packaged into vesicles and exported from the follicular cells into where?
The colloid
What happens to iodide once it is transported into the colloid?
Combines with tyrosine resides to form thyroid hormones
Where are both tyrosine and iodide derived from?
The diet
What is thyroid peroxidase?
Enzyme present on the colloidal side of the cells
Function of thyroid peroxidase
Catalyses the addition of iodide to tyrosine residues is thyroglobulin
In this process iodide loses an electron to become iodine
Addition of one iodine to tyrosine leads to….
MIT (monoiodotyrosine)
Addition of a second iodine to MIT leads to……
DIT (diiodotyrosine)
MIT + DIT = ?
Triiodothyronine or T3
DIT + DIT = ?
Thyroxine or T4
How are thyroid hormones released in response to TSH?
Portions of the colloid are taken back up into the follicular cell by endocytosis. Within the cells they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release the thyroid hormones
Solubility of both T3 and T4
Lipid soluble
Binding of both T3 and T4
They are lipid soluble and so pass across the follicular cell membrane into the plasma, where they bind to plasma proteins, mainly thyroxine-binding globulin
Which of T3 and T4 circulate in the plasma?
Both
What molecules is thyroxine made up of?
2 tyrosine
4 iodine
What molecules is triiodothyronine made up of?
2 tyrosine
3 iodine
Where is thyroxine peroxidase located?
On the apical membrane of the follicular cells
How does iodide enter the follicular cells from the plasma?
Via a Na/I- transporter (symport).
The coupling to Na+ enables the follicular cells to take up iodide against a concentration gradient
How is iodide transported into the colloid?
Via the pendrin transporter
What is iodide transport into the thyroid gland inhibited by?
Thiocyanates
Common origin of thiocyanates
Cigarette smoke
How does TH release into the plasma?
Under influence of TSH from pituitary
TSH stimulates the follicular cells to endocytose colloidal thyroglobulin
How does T3 and T4 circulate in the plasma?
99.8% bound to plasma protein
What does thyroxine binding globulin (TBG) have a particularly high affinity for? What does this result in?
T4
Releasing it slowly into the plasma
This accounts for the longer half life
What is the half life of T4?
Approx. 6 days
What is the half life of T3?
Approx. 1 day
Which of T3 and T4 is there more of in the plasma?
50x more total (free + bound) T4 in plasma than T3
Which of T3 and T4 is more physiologically active?
T3 3-5x more active than T4
90% of TH binding to TH receptors inside cell is either T3 or T4?
T3
Which of T3 or T4 does the TH receptor have a much higher affinity for?
T3
How is T4 turned into T3?
Deiodinated to T3 by deiodinase enzymes
Where is T4 deiodinated into T3?
Half in plasma
Remaining being inside target cells
Effects on TRH from hypothalamus
Cold
Exercise
Pregnancy
What hormones have an inhibitory effect on TRH?
Glucocorticoids
Somatostatin
What do glucocorticoids inhibit?
TSH
Conversion of T4 to T3
What does somatostatin inhibit?
TSH
Effects of thyroid hormones
Raises metabolic rate Promotes thermogenesis Net increase in proteolysis Increase in hepatic gluconeogenesis Net increase in lipolysis Critical for growth - anabolic - stimulates GH receptor expression
Causes of hyperthyroidism
Graves disease
Thyroid adenoma
Pathology of graves disease
Antibodies produced that bind mimic TSH and continually activate the thyroid gland
Increase release of TH switches off TSH release from anterior pituitary so [TSH] in the plasma is very low.
How common is graves disease?
Common
How common is thyroid adenoma?
Rare
Symptoms of hyperthyroidism
Weight loss Heat intolerance Muscle weakness Hyperexcitable reflexes Psychological disturbances Increased HR/Contractable force Cardiac failure
Causes of hypothyroidism
Hashimotos disease
Deficiency in dietary iodine
Idiopathic
What is hashimotos disease?
Autoimmune attack of thyroid gland
How much dietary iodine do we need a year?
50mg/year
Sources of iodine
Mild
Fish
Seafood
Seaweed
Symptoms of hypothyroidism
Weight gain Cold intolerance Brittle nails Thin skin Slow speech/reflexes Fatigue Slow HR Weak pulse
What are thyroid pathologies often accompanied by?
Significant enlargement of thyroid gland = goitre
What is goitre?
Significant enlargement of thyroid gland
Pathology of goitre in hypothyroidism
Increased trophic action of TSH on thyroid follicular cells
Pathology of goitre in graves disease
Over activity as a result of autoimmune disease
