6. Thyroid Flashcards
where is the thyroid gland located
lies across the trachea at the base of the larynx
is the thyroid palpable in health
no - one of the larger endocrine glands (15-20g) but should NOT be palpable in health
what does the thyroid gland do
synthesises thyroid hormones
how many physiologiclly active forms of thyroid hormone are there
2:
T3 - triiodothyronine
T4 - thyroxine
what are the 2 cell types found in the thyroid
- C (clear) cells
2. Follicular cells
what do C cells do
secrete calcitonin (a Ca2+ regulating hormone)
what do follicular cells do
- support thyroid hormone synthesis
- manufacture enzymes to make TH
- produce THYROGLOBULIN (large protein rich in tyrosine residues)
- actively concentrate iodide from the plasma
what are thyroid follicles
spherical structures whose walls are made of follicular cells - centre of the follicle is filled with colloid (where TH stored)
what is colloid
the sticky glycoprotein matrix in the centre of thyroid follicles
how much TH does the thyroid contain in the colloid
2-3 months supply
how does iodide enter into follicular cells
enters from the plasma vi Na+/I- transporter = symport (i.e. Na and I travelling in the same direction)
coupling to Na allows I to move against the concentration gradient into the cell
once in follicular cells, what happens to iodide
transported into the colloid via the pendrin transporter
what inhibits transport of iodide into the thyroid gland
thiocyanates - compounds formed from detoxification of cyanide
what is thyroid peroxidase (aka thyroperoxidase)
enzyme present on the colloidal side of the cells - catalyses addition of iodide to tyrosine resides in thyroglobulin
what does the addition of one iodide to tyrosine form
MIT - monoiodotyrosine
what does the addition of two iodides to tyrosine form
DIT - diiodotyrosine
when iodide is added to tyrosine it looses an electron to form
iodine
how is T3 formed
when MIT and DIT join
how is T4 formed
when DIT and DIT join
what does TSH stimulate
portions of colloid to be taken back up into follicular cells by endocytosis
what happens to the colloid taken back into the follicles by endocytosis
form vesicles which contain proteolytic enzymes
what do the proteolytic enzymes in the vesicles do
cut through thyroglobulin to release thyroid hormones
what allows T3 and T4 to pass from the follicular cell into the plasma
the fact they are both lipid soluble means they can easily pass through cell membranes
what do T3 and T4 do once in the plasma
bind to plasma proteins- mainly thyroxine-binding globulin
what TH circulate in the plasma
BOTH T3 and T4
what percent of T3 and T4 circulate bound to plasma protein
99.8%
why does T4 have a longer half life than T3 - what are theses half lifes
thyroxine binding globulin (TBG) has a very high affinity for T4 and so releases it very slowly into the plasma
T4 half life - around 6 days
T3 half life - around 1 day
what is the only hormone form that exerts an inhibitor effect on TSH and TRH
free hormone
what is the most common form of TH in the plasma
protein bound T4
50x more total (free+bound) T4 in plasma than T3
what TH binds the most to TH receptors inside cell
T3 - makes up 90% of TH that binds to TH receptors
why does more T3 than T4 bind to TH receptors
TH receptors have a much higher affinity for T3 than T4 - means T3 3-5 times more PHYSIOLOGICALLY ACTIVE
why is there more T3 to bind to TH receptors
T4 is deiodinated to T3 by deiodinase enzymes - half in the plasma, half inside the target cells
can the level of deiodinase of T4 activity be altered
yes - can be altered at different times in different tissues to suit demand
what drives continuous secretion and stable [plasma] of TH
thyrothrophic releasing hormone (TRH) released from the hypothalamus
what factors increase TH secretion
cold, exercise, pregnancy
what inhibit TH secretion and how
- glucocorticoids - inhibit TSH and conversion of T4 to T3
3. somatostatins -inhibit TSH
How do TH work
to change transcription and translation to alter protein synthesis in target cells - do this by binding to nuclear receptors
what are the 6 functions of TH
- raise metabolic rate/promote thermogenesis
- increase hepatic gluconeogenesis
- net increase in proteolysis
- net increase in lipolysis
- critical for growth (lack of TH = retarded growth)
- required for foetal brain development
what is hyperthyroidism
thyroid over activated
what are two causes of hyperthyroidism
- graves disease (common)
2. thyroid adenoma (rare)
what is the mechanism behind hyperthyroidism in graves disease
antibodies are produced that mimic TSH so continually activate thyroid - increased release of TH switches off TSH release from ant. pit. - [TSH] plasma very low - thyroid may be 2-3x bigger due to hyperplasia (GOITRE) - hyperactivity in cells
what is the mechanism behind hyperthyroidism in thyroid adenoma
rare thyroid tumour is hormone-secreting - leads to increased hormone levels
what are the four effects of hyperthyroidism
- increased metabolic rate and heat production
- increased protein catabolism
- altered nervous system fucntion
- elevated cardiovascular function - TH is permissive to epinephrine, Beta receptors
what symptoms do increased metabolic rate and heat production cause
weight loss and heat intolerance
what symptoms does increased protein catabolism cause
weight loss and muscle weakness
what symptoms does altered nervous system function cause
hyper-excitable reflexes and physiological disturbances
what symptoms does elevated CV function cause
increased heart rate/contractile force, high output and cardiac failure
what is hypothyroidism
under active thyroid
what are three causes of hypothyroidism
- hashimoto’s disease
- deficiency in dietary iodine
- idiopathic
what is the mechanism behind hypothyroidism in hashimoto’s disease
autoimmune attack of the thyroid gland
what are good dietary sources of iodine
milk, fish, seafood, seaweed
what are 4 effects of hypothyroidism
- decreased metabolic rate and heat production
- disrupted protein synthesis
- altered nervous system function
- reduced CV function
what symptoms arise from decreased metabolic rate and heat production
weight gain and cold intolerance
what symptoms arise from disrupted protein synthesis
brittle nails and thins skin
what symptoms arise from altered nervous system function
slow speech/reflexes and fatigue
what symptoms arise form reduced CV function
slow heart rate and weaker pulse
what is a goitre
thyroid pathology (hyper/hypo) leading to a significant enlargement of the thyroid gland
what is the possible cause of goitre
increased trophic action of TSH on thyroid follicular cells (Hypo)
OR
over activity as a result of autoimmune disease (graves - Hyper)
what is a primary thyroid disease
disease resulting from gland not producing end hormone - could be from iodine deficiency e.g. hashimoto’s
what is a secondary thyroid disease
disease resulting from issue at anterior pituitary e.g. defects
what is a tertiary thyroid disease
disease resulting from issue in the hypothalamus e.g. defects
