Thyroid Gland Flashcards
What are the 2 physiologically active forms of thyroid hormone?
T3 (triiodothyronine) and T4 (thyroxine)
What 2 cell types does the thyroid gland contain?
C (clear) cells
Follicular cells
What do C cells secrete?
Calcitonin (Ca2+ secreting hormone)
What is the function of follicular cells?
Support thyroid hormone synthesis and surround hollow follicles
What is the structure of thyroid follicles?
Spherical structures whose walls are made of follicular cells; centre is filled with colloid (sticky glycoprotein matrix)
How much supply of TH do thyroid follicles contain?
2-3 months
What do follicular cells manufacture?
Enzymes that make thyroid hormones as well as thyroglobulin
What is thyroglobulin?
A large protein rich in tyrosine residues
What happens once the enzymes and thyroglobulin produced by follicular cells are made?
They are packaged into vesicles and exported from follicular cells into the COLLOID
What do follicular cells do with iodide?
Actively concentrate it from plasma and transport it into colloid
What does iodide do once it is transported into the colloid?
Combines with tyrosine residues to form thyroid hormones
Where are tyrosine and iodide derived from?
Diet
How does iodide enter 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
Via what transporter is iodide sent into the colloid?
Pendrin transporter
Enzymes exocytosed into the colloid, along with the thyroglobulin, catalyse what?
Addition of iodide to tyrosine residues on the thyroglobulin molecule
What happens to iodide in the process of being added to tyrosine residues?
Loses an electron to become iodine
Addition of one iodine to tyrosine =
MIT (monoiodotyrosine)
Adding a second iodine =
DIT (diiodotyrosine)
MIT + DIT =
triiodothyronine or T3
DIT + DIT =
tetraiodothyronine or T4
What enzyme are these reactions catalysed by?
Thyroid peroxidase (aka thyroperoxidase)
What happens in response to TSH?
Portions of the colloid are taken back up into the follicular cell by endocytosis
Within the cell they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones
What is the nature of T3 and T4?
Lipid soluble
What do T3 and T4 bind to in the plasma?
Plasma proteins (mainly thyroxine-binding globulin)
Where do both T3 AND T4 circulate?
the plasma
Where are the thyroid hormones stored when their release is not stimulated by TSH?
the colloid
Where is TSH released from?
Pituitary gland
Which thyroid hormone does TBG have a particularly high affinity for?
T4 - releases it slowly into plasma giving it a longer half life than T3
Which hormone is released from the hypothalamus to stimulate TSH production?
TRH
What exerts an inhibitor effect on TSH and TRH
ONLY free hormone
How much of TH in the plasma is free, unbound and physiologically active?
0.2%
Which TH hormone do TH receptors have a higher affiinity for, making it more physiologically active?
T3
What catalyses the deiodination of T4 to T3?
Deiodinase enzymes
How much of T4 is deiodinated in plasma? And where is the remaining fraction deiodinated?
Around half
Inside target cells
In what conditions is TRH release boosted?
Cold
Exercise
Pregnancy
What do somatostatins inhibit in terms of thyroid?
TSH
TH required for GH action
What do glucocorticoids inhibit in terms of thyroid?
TSH and conversion of T4 to T3
Where do THs bind in target cells?
Nuclear receptors
What effect do THs have once bound to receptors?
They change transcription and translation to alter protein synthesis
Give 6 functions of TH in the body
- raises metabolic rate and promotes thermogenesis (futile cycles)
- increases hepatic gluconeogenesis (tho no effect on BG if pancreas functional)
- net increase in proteolysis
- net increase in lipolysis
- critical for growth (stimulates GH receptor expression)
- essential for brain development in utero
What can maternal iodine deficiency result in?
Congenital hypothyroidism/cretinism
2 causes for hyperthyroidism
- Graves disease (common)
- Thyroid adenoma (rare)
Describe the mechanism of Graves
antibodies produced that mimic TSH + continually activate thyroid gland; increased release of TH switches off TSH release from pituitary = TSH plasma v low
What happens to thyroid gland as result of Graves
may be 2-3x normal size due to hyperplasia
What is a thyroid adenoma?
Hormone-secreting thyroid tumour
4 symptoms of hyperthyroidism and the mechanism behind?
- Increased metabolic rate + heat production =
weight loss/heat intolerance - Increased protein catabolism
= muscle weakness/weight loss - Altered nervous system function
= hyperecitable reflexes + psychological disturbance - Elevated cardiovascular function
= increased HR/contractile force, high output, cardiac failure
Give 3 causes of hypothyroidism
- Hashimoto’s disease (autoimmune attack of thyroid gland)
- Deficiency of dietary iodine
- Idiopathic
4 symptoms of hypothyroidism and mechanism behind (same but opposite to hyper)?
1. Decreased metabolic rate + heat production = weight gain/cold intolerance 2. Disrupted protein synthesis = brittle nails/thin skin 3. Altered nervous system function = slow speeches/reflexes, fatigue 4. Reduced cardiovascular function = slow HR/weaker pulse
What is seen in BOTH hyper- and hypo- thyroidism?
Goitre
What is goitre caused by in hypothyroidism?
Increased trophic action of TSH on thyroid follicular cells
What is goitre caused by in Graves?
Over-activity as result of autoimmune disease
What is primary thyroid disease?
When the TG is not working
What is secondary thyroid disease?
When the problem is with the PG
What is tertiary thyroid disease?
When the problem is in the hypothalamus
