Sem 4 Week 11 Lecture 2

Front 1

What is the weight of the thyroid glands?

Back 1

10-20 g

Front 2

Width of lateral lobes?

Back 2

4 cm

Front 3

Blood supply of thyroid glands?

Back 3

-External carotids giving superior thyroid a.
-Subclavian artery giving Inferior thyroid a.

Front 4

Use of thyroid hormones in foetal developments and in infants?

Back 4

Brain and somatic development.

Front 5

What is the main importance of thyroid hormones in adults?

Back 5

Metabolic activity: O2 consumption,protein,carbo,lipid and vitamin metabolism.

Front 6

Where do you find large stores of thyroid?

Back 6

In circulation and in thyroid.(attached to binding proteins)

Front 7

Thyroid hormones levels are not maintained closely within narrow limits.

Back 7

False

Front 8

Main active form

Back 8

T3

Front 9

Biologically inactive thyroid hormone

Back 9

Reverse T3(made up at time of stress/illness)

Front 10

T4 can be produced in other tissues apart from thyroid.

Back 10

FALSE.T4 only made in thyroid glans.

Front 11

T4

Back 11

thyroxine

Front 12

Where is T3 made/

Back 12

-thyroid
-deiodination of I4 in liver,brain.

Front 13

Where does thyroid hormone usually stays within thryoid follicular cell?

Back 13

Colloid droplet-gets ingested from apex of cell and travels twds base to get released in blood.

Front 14

Check the iodide cycle

Back 14

OK!!

Front 15

Iodine

Back 15

Essential for normal thryoid function.

Front 16

Low iodine

Back 16

In mountainous and inland regions

Front 17

Sufficient/excess I2

Back 17

Costal regions

Front 18

Recommended daily intake of iodine in adults

Back 18

150g

Front 19

Iodine daily intake is high in

Back 19

Pregnant women.200-250g

Front 20

Dietary sources of Iodine

Back 20

Bread,salt,medical products(cough syrups,vitamins,antiseptics)

Front 21

Heart drug having large amt of Iodine in it.

Back 21

Amiodarone

Front 22

Iodine gets reduced before absorption to

Back 22

Iodide

Front 23

Principal site of I2 absorption

Back 23

Small intestine

Front 24

Is absorption virtually complete?

Back 24

Yes

Front 25

Plasma conc. of inorganic Iodide is

Back 25

< 1 microgram/L

Front 26

Iodide is removed from plasma by

Back 26

thyroid and kidneys

Front 27

Iodide also appears in

Back 27

Breast milk and sweat.

Front 28

Amt of Iodide perfusing thyroid being removed in each passage

Back 28

20 %

Front 29

Normal thyroid maintains a conc. of Iodide which is

Back 29

20-50 times higher than that of plasma

Front 30

Which protein responsible for transport and where is it found?

Back 30

Sodium/Iodide transporter(NIS)
-in thyrocyte basal mb

Front 31

What increases iodide transport activity?

Back 31

Chronic TSH stimulation

Front 32

NIS is a protein of

Back 32

643 a.a with 13 mb spanning domains.

Front 33

Carboxy terminus of NIS is

Back 33

INSIDE cell( and amino is outside)

Front 34

What first binds to transporter?

Back 34

Na+ which forms a complex in presence of Iodide--->transfers 2Na+ and iodide inside cell.

Front 35

Gene for NIS located on

Back 35

chrm 19p

Front 36

main cell inside thyroid gland

Back 36

thyrocyte

Front 37

Protein which transports iodine from cell to lumen

Back 37

Pendrin-Cl-/I- transporter across thyroid apical mb.(genetic abno. leads to goitre)

Front 38

Other transporter from cell to lumen

Back 38

Apical Iodide Transporter(ATI)-passive iodide transport activity.

Front 39

Check diagram of thyroid hormone synthesis

Back 39

OK

Front 40

Iodide oxidized by

Back 40

Thyroid peroxidase(requires H2O2)

Front 41

Iodide covalently bound to what in the exocytotic vesicles fused with apical cell mb.

Back 41

Tyrosyl residues of thyroglobulin.

Front 42

Thyroid peroxidase(TPO)

Back 42

Protoporphyrin-IX heme protein uniquely expressed in thyroid.

Front 43

What rapidly increases Thyroid peroxidase mRNA transcription?

Back 43

TSH or cAMP

Front 44

TPO synthetized where?

Back 44

on polysomes

Front 45

TPO undergoes glycosylation where?

Back 45

Golgi apparatus.

Front 46

With what is thyroid peroxidase packaged into exocytotic vesicles?

Back 46

Thyroglobulin

Front 47

TSH stimulate mvt of vesicles to

Back 47

Apical mb.

Front 48

TPO found in

Back 48

mb-associated with microvilli.

Front 49

C-terminal of TPO is

Back 49

Hydrophobic

Front 50

C-terminal of TPO is on

Back 50

Apex of microvilli.

Front 51

H202 produced from

Back 51

NADPH thyroid oxidase

Front 52

TPO is an enz. that helps to

Back 52

bind Iodine onto tyrosine.

Front 53

Iodine and tyrosine have

Back 53

Separate binding sites on enzyme.(each oxidised by loss of 1 electron)

Front 54

Iodine and tyrosine combine to form

Back 54

Iodotyrosine

Front 55

What is the most abundant protein in the thyroid?

Back 55

Thyroglobulin

Front 56

Main function of thyroglobulin(TG) is

Back 56

Provide peptide backbone for synthesis and storage of thyroid hormones.

Front 57

Each TG molecule contains abt

Back 57

140 tyrosyl residues

Front 58

TG coded by

Back 58

gene on chrm 8 & consists of 2 identical subunits bound together by ionic and disulphide bonds

Front 59

How long is iodinated TG stored for in colloid?

Back 59

hours to 100 days

Front 60

How is TG resorbed into the cell?

Back 60

micropinocytosis

Front 61

TG is degraded into iodothyronines in

Back 61

Lysosomes

Front 62

TG measurement is relevant

Back 62

In follow up of pts with thyroid cancer.If TG present in circulation,recurrence of cancer.

Front 63

How is iodothyronine formed?

Back 63

Iodinated hydroxyphenol group of 1 iodotyrosine residue to phenolic hyroxyl of another

Front 64

TPO is also responsible for

Back 64

Coupling

Front 65

2 diodotyrosine residues couple within 1 TG molecule to give

Back 65

T4

Front 66

1 monoiodotyrosine and 1 diodotyrosine couple within 1 TG to give

Back 66

T3

Front 67

In what form is thyroglobulin resorbed in follicular cell?

Back 67

Colloid droplets

Front 68

TG hydrolyzed to

Back 68

T4 and T3---> ECF then circulation

Front 69

Most thyroid hormones made in

Back 69

Colloid

Front 70

Deiodination of T4 to T3 leads to

Back 70

Increased biological activity

Front 71

T4

Back 71

-produced at 80-100ug/day
-degraded at 10%/day
-80% deiodinated(40% to T3,40% to rT3)

Front 72

T3

Back 72

triiodothyronine

Front 73

T3

Back 73

-80% produced by extrathyroidal deiodination of T4 and rest by thyroid.
-production rate 30-40 ug/day

Front 74

rT3

Back 74

all produced by extrathyroidal deiodination of T4(30-40 ug/day)

Front 75

What are the serum binding pz for thyroid hormones?

Back 75

-Thyroxine Binding globulin(TBG)
-Transthyrethrin
-Albumin
-Lipopz

Front 76

TBG binds

Back 76

75 % of circulating T4(also binds T3/rT3)

Front 77

Fraction of TBG in serum containing T4

Back 77

1/3

Front 78

TBG synthetized where?

Back 78

Liver

Front 79

Increased estrogen levels

Back 79

Increase TBG

Front 80

Androgens

Back 80

Decrease TBG

Front 81

What determines biological activity?

Back 81

FREE T4 and T3

Front 82

What delays hypothyroidism if thyroid secretion ceases?

Back 82

T4 stored in serum.

Front 83

Thyroxine(T4)

Back 83

-75% bound to TBG
-10% bound to TTR
-12% to albumin
-3% to lipopz
-0.03 % free in serum(10-26 pmol/L)

Front 84

T3

Back 84

-80% bound to TBG
-5% bound to TTR
-15% to albumin and lipopz
-0.3% free(3-6pmol/L)

Front 85

Wolff-Chaikoff effect is

Back 85

Inhibition of organification of iodide with sudden exposure to excess serum Iodide-decreased hormone biosynthesis.(resumes in 2-4 wks)

Front 86

T4/T3 can dissociate from binding pz instantaneously.

Back 86

True

Front 87

T4/T3 enter cells by

Back 87

processes that energy dependent or Na+ dep.

Front 88

Transporters for cellular uptake of thyroid hormones?

Back 88

-monocarboxylate transporter(MCT8)
-OATP1

Front 89

MCT8

Back 89

-gene on chrm Xq13.2
-mutations of MCT8 assoc. with psychomotor retardation/ elevated T3 levels.
-MCT8 role in T3 supply to neurons.

Front 90

How many enz. catalyze deiodination?

Back 90

3.
-D1 in liver,kidneys and thyroid
-D2 in brain,pituitary,muscle,heart.
-D3 in brain,placenta,foetal tissues.

Front 91

Clinical thyroid disorders assoc. with

Back 91

Iodine metabolism and thyroid hormone production.

Front 92

Iodine deficieny

Back 92

Global problem where soil is deprived of Iodine-assoc. with cretinism.

Front 93

Australia is

Back 93

Deficient in Iodine

Front 94

Myxedematous Endemic Cretinism:

Back 94

-Dwarfism
-Retarded sexual dev.
-Puffy features
-Dry skin and hair
-Severe mental retardation

Front 95

Hashimoto's thyroiditis clinical features:-

Back 95

-Dislike of cold
-Demand for warmer room or more clothing
-Decrease in activity due to listlessness,lack of energy and fatigue
-mental dullness/drowsiness
-Constipation
-Increased menstrual flow
-Hair loss
-dizziness

Front 96

In Hashimoto's,

Back 96

T4 is low and TSH high (high levels of Thryoid peroxidase Ab and thyroglobulin Ab present)

Front 97

Commonest cause of Hypothyroidism is

Back 97

Hashimoto's

Front 98

What happens in Hashimotos?

Back 98

-Gradual thyroid failure,goitre or both due to autoimmune mediated destruction of thyroid follicular cells.

Front 99

What kind of cells infiltrate thyroid gland in Hashimotos?

Back 99

Lymphocytes

Front 100

T4/T3 regulation via negative feedback is by acting on

Back 100

Hypothalamus,releasing TRH if low T4/T3---> act on pituitary to release TSH.

Front 101

Lab. dx of Hypothyroidism:-

Back 101

-Total and free T4 down
-Total and free T3 down
-Increased TSH if primary hypothyroidism but can be NORMAL /DECREASED if central hypothyroidism(e.g pituitary tumours)

Front 102

Useful tests to dx hypothyroidism :-

Back 102

-thyroid Ab
-thyroglobulin
-thyroid peroxidase.

Front 103

Tx of hypothyroidism in pts < 60 y.o and in absence of ischemic HD :-

Back 103

Thyroxine 50-100g orally daily with increase over 3-6 months to 100-200 ug/day