Thyroid Gland Flashcards
What is the thyroid gland?
- one of the larger endocrine glands
- shaped like a butterfly
- lies across the trachea at the base of larynx
- it isn’t visible or palpable in health
How much does the thyroid gland weigh?
15-20g
What does the thyroid gland synthesise?
thyroid hormones
- T3 (triiodothyronine)
- T4 (thyroxine).
What are the 2 cell types that the thyroid gland contains?
- C (clear) cells
- Follicular cells
What are thyroid follicles?
spherical structures whose walls are made of follicular cells
What do C cells secrete?
Calcitonin (Ca regulating hormone)
What do follicular cells do?
- manufacture enzymes that make thyroid hormones as well as thyroglobulin
- actively concentrate iodide from the plasma and transport it into the colloid where it combines with the tyrosine residues to form the thyroid hormones
What is colloid?
Sticky glycoprotein matrix at centre of follicle
What do thyroid follicles contain?
2-3 months supply of TH
What do follicular cells manufacture?
enzymes that make thyroid hormones as well as thyroglobulin (a large protein rich in tyrosine residues)
What are packaged into the colloid?
The enzymes and thyroglobulin are secreted from the follicular cells into the colloid.
What are tyrosine and iodine derived from?
Diet
What catalyses the reaction of tyrosine to T4 and T3?
Thyroid peroxidase
Where is thyroid peroxidase located?
On the apical membrane of the follicular cells
How does iodide enter the follicular cell?
- Iodide enters the follicular cells from the plasma
- via a Na+/I- transporter (symport)
- 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
.
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What does addition of iodine to tyrosine result in?
MIT (monoiodotyrosine)
What doe a second iodine to MIT result in?
DIT (diiodotyrosine)
MIT+ DIT=
T3 (trriodotyronine)
DIT + DIT =
T4 (tetraiodothyronine)
How does colloid respond 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
How do T3 and T4 exit the cell?
Both T3 and T4 are lipid soluble and so pass across the follicular cell membrane into the plasma
How are T3 and T4 circulated in the blood?
bind to plasma proteins, mainly thyroxine binding globulin (TBG)
What is movement of TH from colloid to plasma under the influence of?
TSH released from the pituitary
What does TSH stimulate?
Stimulates the follicular cells to endocytose colloidal thyroglobulin
What happens to thyroid hormones when follicular cells are not stimulated?
They are stored in the colloid
Why does T4 have a longer half life than T3?
Thyroxine Binding Globulin (TBG) has particularly high affinity for T4 releasing it only slowly into the plasma. This accounts for the longer half life of T4:
- T4 ~ 6 days
- T3 ~ 1 day
What percentage of T3 and T4 circulate in the plasma bound to plasma protein?
More than 99.8%
What form of hormone exerts an inhibitor effect on TSH and TRH
Free hormone
In what form does most TH circulate?
-50x more total T4 in plasma than T3
protein bound
T4: ~100nmoles/l
T3: ~2.3nmoles/l
(note: free TH is in picomolar range (1000x smaller)).
Why is 90% of TH binding to TH receptors inside cells T3?
TH receptor has a much higher affinity for T3 than T4
T3 is 3-5 times more physiologically active than T4
How does T4 become T3?
T4 is deiodinated to T3 by deiodinase enzymes
Where is T4 converted to T3?
Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells
What do glucocorticoids inhibit?
TSH and conversion of T4 to T3
What does somatostatin inhibit?
TSH
What do THs trigger when they bind to nuclear receptors in the target cells?
They change transcription and translation to alter protein synthesis.
What are the 6 functions of thyroid hormone?
- 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)
- Required for foetal brain development (deficiency= congenital hypothyroidism)
What can cause congenital hypothyroidism?
Dietary iodine deficiency in the mother
Why is TH critical for growth?
stimulates GH receptor expression
Give 2 causes of hyperthyroidism.
- Grave’s disease
- Thyroid adenoma
What is a thyroid adenoma?
Hormone secreting thyroid hormone
What happens in Grave’s disease?
- antibodies produced that 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 hyperplasia. hyperactivity of cells also apparent.
What are the symptoms of hyperthyroidism?
increased metabolic rate and heat production
-> weight loss/ heat intolerance
increased protein catabolism
-> muscle weakness/ weight loss
altered nervous system functions
-> hyperexcitable reflexes and psychological disturbances
elevated cardiovascular function
-> increased HR/contractile force, high output, cardiac failure
Why do you get weight loss/ heat intolerance in hyperthyroidism?
Increased metabolic rate and heat production
Why do you get muscle weakness/ weight loss in hyperthyroidism?
Increased protein catabolism
Why do you get Hyperexcitable reflexes and psychological disturbances in hyperthyroidism?
Altered nervous system function
Why do you get increased HR/contractile force, high output and cardiac failure in hyperthyroidism?
Elevated cardiovascular function. TH is permissive to epinephrine, B receptors
Give 3 causes of hypothyroidism.
- hashimoto’s disease
- deficiency in dietary iodine
- idiopathic
What is Hashimoto’s disease?
Autoimmune attack of thyroid gland
What are sources of iodine?
- milk
- fish
- seafood
- seaweed
How much iodine do we need a year?
50mg/year
What may idiopathic hypothyroidism 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
Why do you get weight gain/cold intolerance in hypothyroidism?
Decreased metabolic rate and heat production
Why do you get brittle nails/thin skin in hypothyroidism?
Disrupted protein synthesis
Why do you get slow speech/reflexes and fatigue in hypothyroidism?
Altered nervous system function
Why do you get slow heart rate/weaker pulse in hypothyroidism?
Reduced cardiovascular function
Goitre
Significant enlargement of the thyroid gland (hypertrophy)
What is goitre associated with?
Thyroid pathologies (hypo and hyperthyroidism)
What may cause goitre formation?
- increased trophic action of TSH on thyroid follicular cells (hypothyroidism)
- over-activity as a result of autoimmune disease (Graves Disease)