The Thyroid Gland Flashcards
What are the two physiologically active forms of thyroid hormones?
T3 - Triiodothyronine
T4 - Thyroxine
What are the 2 cell types of cell in the thyroid gland?
What is there function?
- C (clear) cells which secrete calcitonin (a hormone involved in calcium regulation)
- Follicular cells which support thyroid hormone synthesis and surround hollow follicles
What are thyroid follicles?
Spherical structures filled with colloid
Walls are made of follicular cells
Colloid is a sticky glycoprotein matrix
Contains arund 2-3 months supply of TH
How do the follicular cells suport thyroid hormone production?
Manufacture enzymes that make thyroid hormones as well as thyroglobulin
What is thyroglobulin?
Large protein
Contains many tyrosine residues
How do follicular cell derived enzymes and thyroglobulin enter the collid?
The enzymes and thyroglobulin are packaged into vesicles and exported from the follicular cells into the colloid.
What is the role of follicular cells and iodide?
Actively concentrate iodide from the plasma and transport it into the colloid where it combines with the tyrosine residues to form the thyroid hormones
Where do iodide and tyrosine come from?
The diet
What is the precursor for thyroxine and triiodothyronine?
Both derived from tyrosine
What is the enzyme responsible for thyroid hormone synthesis?
Thyroid peroxidase - found on the apical membrane of follicular cells
How does iodide travel from the plasma to the colloid?
Iodide enters the follicular cells from the plasma via Na+/I- transport (symport). The coupling enables the follicular cells to take up iodine against a concentation gradient.
Iodide is then transported into the colloid via the pendrine transporter
What is the effect of thiocyanates on iodide transport?
Iodide transport into thyroid gland is inhibited by thiocyanates, compounds formed from detoxification of cyanide. Common origin is cigarette smoke.
Look
Important to note that both sodium and iodine are transported into the cell
Also thyroglobulin is made in the follicular cell and transported into the colloid
Notice pendrine and sodium/iodide transporter
What is the action of thyroid peroxidase?
Catalyses the addition of iodide to tyrosine residues in thyroglobulin
(iodide loses and electron to become iodine)
What hormones are made when iodide starts to get added to tyrosine?
Addition of one iodine to tyrosine = MIT (monoiodotyrosine).
Adding a second iodine = DIT (diiodotyrosine).
MIT and DIT then undergo reactions where:
MIT + DIT = triiodothyronine or T3, or
DIT + DIT= tetraiodothyronine or Thyroxine T4.
What happens to the colloid in response to TSH?
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 thyroid hormones.
What happens once the thyroid hormones are released from thyroglobulin by the proteolytic enzymes?
Both T3 and T4 are lipid soluble and so pass across the follicular cell membrane into the plasma, where they bind to plasma proteins, mainly thyroxine-binding globulin.
Both T3 and T4 circulate in the plasma
What releases TSH?
The pituitary
If there is no stimulation by TSH, where are the thyroid hormones stored?
Stored within the colloid
What proportion of T3 and T4 circulates in the plasma bound to plasma protein?
99.8% §
Why does T4 have a longer half life than T3?
T4 half life is - around 6 days
T3 half life is around 1 day
Thyroxine binding has particularly high affininty for T4 releasing it slowly into the plasma
What chemical mediators are responsible for the negative feedback on the anterior pituitary and the hypothalamus?
Hypothalamus produces TRH
Anterior pituitary produces TSH
Only free hormone (unbound T4 or T3) exerts an inhibitor effect on TSH and TRH
What form of the thyroid hormone is most common?
Most TH circulates in the form of protein bound T4 ~100nmoles/l, while T3 is only ~2.3nmoles/l (note: free TH is in picomolar range (1000x smaller)).
Why is the majority (90%) of the TH binding to TH receptors inside cells by T3?
The TH receptor has a much higher affinity for T3 than T4 making T3 3-5 times more physiologically active than T4
T4 is deiodinated to T3 by deiodinase enzymes - where does this happen?
Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells
The level of deiodinase activity can be altered at different times in different tissues to suit demand.
What is responsible for the continuos secretion of thyroid hormone?
As a result of TRH release from the hypothalamus
What factors increase the release of thyroid releasing hormone?
Cold, exercise and pregnancy
What is the effect of glucocorticoids and somatostatin on TSH?
Glucocorticoids inhibit TSH and conversion of T4 to T3 (iodinase)
Somatostatin inhibits TSH
What are the receptors for thyroid hormone function?
Nuclear receptors in target cells
They change transcription and translation to alter protein synthesis
What is the effect on the body of thyroid hormones?
raises metabolic rate and promotes thermogenesis
increase hepatic gluconeogenesis
net increase in proteolysis
net increase in lipolysis
critical for growth (lack of TH results in retarded growth)
- anabolic
- stimulates GH receptor expression (thyroid hormones are permissive to GH)
required for foetal brain development (deficiency = congenital hypothyroidism)
- can be caused by dietary iodine deficiency in the mother
What are the causes of hyperthyroidism?
- Graves Disease - (common) antibodies produced that bind mimic TSH and continually activate the thyroid gland. Increased release of TH switches off TSH release from anterior pituitary so [TSH]plasma very low. Thyroid gland may be 2-3x normal size due to hyperplasia. Hyperactivity of cells also apparent.
- Thyroid Adenoma - (rare ) hormone-secreting thyroid tumour
What are symptoms of hyperthroidism?
- Increased metabolic rate and heat production
- weight loss/ heat intolerance - Increased protein catabolism
- muscle weakness/weight loss - Altered nervous system function
- hyperexcitable reflexes and psychological disturbances - Elevated cardiovascular function. TH is permissive to epinephrine, b receptors
- increased HR/contractile force, high output, cardiac failure
What are the causes of hypothyroidism?
- Hashimoto’s Disease - autoimmune attack of thyroid gland
- Deficiency in dietary iodine – only 50mg/year(!) required but many areas of the world soil has insufficient quantities. Main source of dietary iodine was table salt which was enriched with iodine. But no longer in the UK! Milk, Fish, seafood and seaweed are good sources.
Idiopathic – no known cause, may be linked to thyroiditis
What are the symptoms of hypothyroidism?
- Decreased metabolic rate and heat production
- weight gain/cold intolerance - Disrupted protein synthesis
- brittle nails/thin skin - Altered nervous system function
- slow speech/reflexes, fatigue - Reduced cardiovascular function
- slow heart rate/weaker pulse
What are goitres?
•Thyroid pathologies (hypo- and hyperthyroidism) are often accompanied by significant enlargement of the thyroid gland
What causes the goitre formation?
•Goitre formation may be caused by increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves Disease)
Results in hypertrophy of the thyroid gland
Description of diagram:
Hypothyroidism (left) - there is not much T4/T3 therefore, the TSH concentration increases in an effort to make more, however T4/T3 cannot be made since there is no iodine and the cycle continues
Hyperthyroidism (right)
Thyroid stimulating immunoglobulins continuously stimulate the production of T3/T4 by imitating TSH
Look
Primary disorder because the gland producing the hormone is not working correctly
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So hypothyroidism (left) - there is no negative feedback from T3/T4
Hyperthyroidism - Strong negative feedback but it makes no difference - auto antibodies mimic TSH and don’t respond to negative feedback
Remember Graves will have a low TSH
