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3d week 2 - hormones > physiology of thyroid and the HPT axis > Flashcards

physiology of thyroid and the HPT axis Flashcards

1
Q

HP-thyroid axis

A

hypothalamus (paravenricular nucleus) -> TRH release -> pituitary gland -> TSH release -> blood -> thyroid gland -> T3/T4 (aka thyroid hormone) release

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2
Q

how is T3/T4 transported through the body

A

bound to Thyroxine-binding globulins in the blood

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3
Q

role of thyroid hormone on bone

A

normal bone growth, turnover and mineralisation

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4
Q

role of thyroid hormone on muscle

A

normal muscular function and development

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5
Q

general role of thyroid hormone in all cells (6)

A
  1. increases basal metabolic rate
  2. increase O2 usage
  3. LDL uptake (i.e. removal of bad cholesterol from the blood)
  4. lipolysis
  5. glyolysis
  6. gluconeogenesis
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6
Q

what connects the two ‘wings’ of they thyroid gland

A

isthmus

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7
Q

how much does a normal thyroid gland weigh

A

15-20g

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8
Q

what is a large thyroid gland known as

A

a goitre -> may be associated with dysregulation of thyroid hormone biosynthesis

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9
Q

what is the pyramidal lobe of the thyroid

A

a normal anatomic variant representing a superior sliver of thyroid tissue arising from the thyroid isthmus - some people have a small part that sticks up

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10
Q

what is the thyroid gland made of (histologically)

A

follulcular cells surrounding colloid

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11
Q

what is the height of the follicular cells dependent on

A

activation by TSH

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12
Q

what is the colloid

A

the store of thyroid hormone in the thyroid gland - made of thyroglobulin

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13
Q

what are parafollicular cells and what do they do

A

they are cells cells situated between follicles that synthesize, store, and secrete calcitonin

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14
Q

what are the 2 prinicipal products of the thyroid gland

A
  1. thyroxine (T4)
  2. triiodo-L-thyronine (T3)
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15
Q

why is iodine key in diet

A

iodine is a key component to T3/4 formation -> the thyroid hormones are all based on the esterification of 2 tyrosine molecules which are then iodinated

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16
Q

T3 vs T4 iodine structure

A

T3 has 3 iodines per molecule;
T4 has 4 iodines per molecule

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17
Q

what is reverse T3

A

an isomer of T3 that is biologically inactive

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18
Q

which thyroid hormone is the most biologically active

A

T3

T4 is converted into T3 within cells

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19
Q

what is the major hormone produced by the thyroid gland

A

T4 - it is a store for T3

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20
Q

what is another name for thyroid hormone enzymes

A

deiodinases

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21
Q

what kind of proteins are deiodinases

A

selenoproteins -> active Se metal at the active site

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22
Q

what is the cofactor for the deiodinisation reaction (T4->T3)

A

glutathione

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23
Q

what are the 3 types of deiodinases and where are they expressed

A
  1. type 1 -> present in thyroid, liver, kidney;
  2. type 2 -> expressed everywhere;
  3. type 3 -> expressed in brain and placenta
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24
Q

which deiodinase is the major converter of T4->T3 in circulation

A

type 1 deiosinase

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25
Q

what drug is type 1 deiodinase sensitive to

A

propylthiouracil

26
Q

examples of food that contain iodine

A

fish (cod, tuna etc.); seaweed; shrimp; dairy products; iodised salt

27
Q

why is salt fortified with iodine in many countries

A

to stop iodine deficiencies which can lead to things like neonatal hypothyroidism

28
Q

what does deiodinase 3 do

A

it inactivates T4 (by turning it into rT3) and T3 (by further metabolising it to 3,3’-diiodothyronine

29
Q

how much iodine is needed to be ingested per day

A

150 micrograms, 200 in pregnancy

30
Q

where is the majority of iodine excreted

A

in the urine (15% in stool)

31
Q

how much iodine is used by the kidney

A

75 micrograms -> BUT 25 mcg is put back

32
Q

what organs absorb iodine

A

placenta, mammary glands, colon, stomach

33
Q

what are the 2 key receptors in the basolateral membrane of the thyroid follicular cell and what do they do

A
  1. N+/I- symporter -> allows iodine to enter the cell;
  2. TSH receptor -> TSH must bind in order for TH production to be stimulated
34
Q

what cells produce TSH

A

thyrotrophs in the pit gland

35
Q

what is the alpha subunit of TSH almost identical to

A

the alpha subunit of hCG, LH and FSH

36
Q

what is the TSH alpha subunit thought to be responsible for

A

stimulation of adenylate cyclase -> needed for generation of cAMP

37
Q

what determines the receptor specificity of TSH

A

the beta subunit -> this is unique to TSH

38
Q

other than the thyroid gland, where else is are TSH receptors present and why is this clinically significant

A

orbital muscle cells -> can result in ophthalmological conditions like thyroid eye disease -> proptosis can occur

39
Q

what kind of antibodies are seen in grave’s disease

A

thyroid stimulating antibodies

40
Q

what kind of antibodies are seen in hashimoto’s disease

A

thyroid inhibiting antibodies -> less cAMP productions

41
Q

what are the 6 steps of thyroid hormone biogenesis

A
  1. iodide uptake
  2. thyroglobulin synthesis
  3. hydrogen peroxide generation
  4. organification
  5. coupling
  6. uptake and breakdown of colloid
42
Q

where is thyroglobulin secreted into after being make by follicular cells

A

the colloid space

43
Q

what protein is essential in the secretion of iodine from the follicular cell into the colloid space

A

pendrin (see notes)

44
Q

what do babies with congential pendrin absence present with (2)

A
  1. kidney tube dysfunction
  2. sensorineural hearing loss
45
Q

apart from the thyroid, what other organ is pedrin present in

A

the kidneys

46
Q

what occurs in the peroxidation step of T3/T4 synthesis (2)

A
  1. H2O2 is generated by DUOX2 (stimulated by IP3 and Ca2+)
  2. H2O2 reacts with iodine and prepares it for binding with the tryosyl residues
47
Q

what is the organification step in T3/T4 synthesis

A

incorporation of iodine into thyroglobulin by Thyroid peroxidase (TPO) -> MIT/DIT residues formed

48
Q

describe the coupling mechanism of T3/T4 synthesis

A
  1. 2 DIT molecules are brought together to form T4
  2. 1 MIT and 1 DIT are brought together to form T3
    this is done by TPO -> stored in colloid
49
Q

describe the uptake and breakdown of colloid in T3/T4 synthesis

A
  1. thyroglobulin with in situ T3 and T4 is taken up into follicular cells by endocytosis
  2. cathepsins in lysosomes breakdown thyroglobulin -> releases T3/T4
  3. T3/T4 pass out of the follicular cell via MCT8/10
  4. free MIT/DIT is diodinated by iodotyrosine dehalogenase which allows MIT/DIT to be stored
50
Q

in biochemical analysis, what form or T3/T4 is measured

A

free T3/T4 (i.e. not protein bound)

51
Q

what proteins bind to T3/T4 (when circulating in the blood -3)

A
  1. thyroid binding globulin 60-70% (more in pregnancy, hepatitis and chronic heroine use)
  2. transthyretin 10%
  3. albumin 20%
51
Q

why are thyroid hormones bound to proteins when circulating (2)

A
  1. provides a pool of thyroid hormones
  2. increases the half life -> T4 for 8 days and T3 for 24hrs
52
Q

where does the T4 -> T3 conversion usually occur

A

inside the target organ cells

53
Q

what enzyme is responsible for T4 -> T3 conversion

A

3’/5’ monodeiodinase

54
Q

how does T3 act to produce an effect on a cell

A
  1. enters the cell nucleus and binds to Thyroid Hormone Receptor (THR) and Retinoid X Receptor (RXR)
  2. these alter the transcription of certain genes (promoting or inhibiting)
  3. proteins promoting certain actions e.g. Na+/K+ pump, myosin heavy chains,respiratory enzymes etc. are produced
55
Q

what are futile cycles

A

a set of biochemical reactions that concurrently run in opposite directions, consuming ATP in one of the directions e.g breaking down proteins but also building them upw

56
Q

why do futile cycles occur

A

to expend energy and burn fat, and to increase O2 demands

57
Q

how does increased fat mass result in thyroid hormone production

A

increased fat -> increased leptin -> stimulated HPT axis -> TH produced in an attempt to burn fat

58
Q

other than T3/4 what other molecules can inhibit TSH secretion

A
  1. DA
  2. somatostatin
59
Q

what is the direct T3/4 -ve feedback lool

A
  1. inhibition of TSH production (action of TRHR)
  2. inhibtion of TRH binding
60
Q

what is the indirect -ve feedback loop of T3/4

A

reduced the sensitivity to TRHRs

61
Q

when might low/normal T3 and T4 be seen but with a normal TSH

A

in illness

3d week 2 - hormones (8 decks)

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