The Thyroid gland Flashcards
How much does a normal thyroid gland weigh?
15-20g
What two hormones does the thyroid gland secrete?
T3 (triiodothyronine) – most active form, receptors have higher affinity for T3
T4 (thyroxine) – most circulates as this
Whats the other name for T3?
triiodothyronine
What is the other name for T4?
thyroxine
Which of the 2 hormones produced by the thyroid is more physiologically active?
Triiodothyronine (receptors have a higher affinity for T3)
Which hormone has a higher concentration in serum?
T4
What 2 cells are found in the thyroid gland?
C (clear) cells which secrete calcitonin (Ca2+ regulating hormone)
Follicular cells that support thyroid hormone synthesis and surround hollow follicles.
Describe the structure and contents of follicles in the thyroid gland
Thyroid follicles are spherical structures whose walls are made of follicular cells. Centre of follicle filled with colloid = sticky glycoprotein matrix. Contain 2-3 months supply of TH.
What cells produces the enzymes required to produce the thyroid hormones?
Follicular cells
What do the follicular cells produce to aid in thyroid hormone production?
Enzymes responsible for TH production
Thyroglobulin (covered in tyrosine residues for TH production)
What enzyme catalyses TH synthesis?
thyroid peroxidase
What allows transport of iodine into follicular cells for thyroglobulin production?
Na+/I- transporter symport
The coupling to Na+ (which follows its concentration gradient) enables the follicular cells to take up iodide against its own concentration gradient.
How does iodine then enter the colloid from the follicular cells?
(Thyroglobulin with iodine residues is endocytose to the colloid)
Free iodine is then exported via pendrin transporter to the colloid, where it can be ionised and used for TH formation
What compounds can inhibit iodine transport into the thyroid gland?
Thiocyanates - compounds formed from detoxification of cyanide. Common origin is cigarette smoke.
What transporters release THs into the bloodstream from the follicular cells?
Released from the cells via monocarboxylate transporters into the bloodstream following exocytosis from the colloid after TSH stimulation
What plasma proteins bind to TH hormones and why?
Bind to thyroxine-binding globulin, allows transport of lipid soluble hormones
What % of T3 and T4 in plasma are protein bound?
99.8%
To which TH does thyroxine binding globulin have a higher affinity for, resulting in its longer half life in plasma?
Thyroxine Binding Globulin (TBG) has a particularly high affinity for T4, releasing it only slowly into the plasma. This accounts for the longer half life of T4:
o T4 ~ 6 days
o T3 ~ 1 day
What has an inhibitor effect on TSH and TRH?
Free T3 and T4 - negative feedback loop
What are the circulating levels of T4 and T3?
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)
What % of TH binding to TH receptors is to T3?
90%
What converts T4 to T3?
deiodinase
What % of T4 is deiodinated to T3 in plasma?
50% (rest is deiodinated within target cells)
What stimuli increase TRH release?
Cold
Exercise
Pregnancy
What hormones inhibit TSH release?
Glucocorticoids
Somatostatins
What are the functions of thyroid hormones?
o Raises metabolic rate and promotes thermogenesis
o Increase hepatic gluconeogenesis
o Net increase in proteolysis (catabolic)
o Net increase in lipolysis
o Critical for growth (role in GH signalling)
o Required for foetal brain development
How does thyroid hormones influence GH signalling?
Stimulates GH receptor signalling to potentiate its effects on growth
How are thyroid hormones essential for foetal brain development, and what causes it?
(deficiency = congenital hypothyroidism)
TH hormone deficiency can be caused by dietary iodine deficiency in the mother. Leads to cognitive defects in the new-born
What can cause congenital hypothyroidism?
Anatomical defect of the thyroid gland
Iodine deficiency
Inborn error of thyroid metabolism
List two causes of hyperthyroidism
Graves disease - common, antibodies mimicking TSH continuously stimulate TH production
Thyroid adenoma - rare hormone secreting thyroid cancer
List the features of Graves disease
Graves 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 may be 2-3x normal size due to hyperplasia (goitre)
Hyperactivity of cells also apparent.
List the symptoms of hyperthyroidism and why they occur
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, β receptors = increased HR/contractile force, high output, cardiac failure
List 3 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
List the symptoms of hypothyroidism and why they occur
Decreased metabolic rate and heat production = weight gain/cold intolerance (lost catabolic effect to produce energy)
Disrupted protein synthesis = brittle nails/thin skin
Altered nervous system function = slow speech, reflexes, fatigue
Reduced cardiovascular function = slow heart rate, weaker pulse
What is goitre and what causes it?
Thyroid pathologies (hypo- and hyperthyroidism) are often accompanied by significant enlargement of the thyroid gland, which is termed goitre
Goitre formation may be caused by:
- increased trophic action of TSH on thyroid follicular cells (hypothyroidism)
- over-activity as a result of autoimmune disease (Graves Disease) which results in hypertrophy (overgrowth) of thyroid gland
How are goitres treated?
Treatment for a goitre can include medication, hormone therapy and surgery (e.g. thyroidectomy).
The treatment you receive will depend on:
o The size of the goitre
o The symptoms the goitre is causing
o Whether you have any underlying thyroid condition
