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103 Cards in this Set

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What is the weight of the thyroid glands?
10-20 g
Width of lateral lobes?
4 cm
Blood supply of thyroid glands?
-External carotids giving superior thyroid a.
-Subclavian artery giving Inferior thyroid a.
Use of thyroid hormones in foetal developments and in infants?
Brain and somatic development.
What is the main importance of thyroid hormones in adults?
Metabolic activity: O2 consumption,protein,carbo,lipid and vitamin metabolism.
Where do you find large stores of thyroid?
In circulation and in thyroid.(attached to binding proteins)
Thyroid hormones levels are not maintained closely within narrow limits.
False
Main active form
T3
Biologically inactive thyroid hormone
Reverse T3(made up at time of stress/illness)
T4 can be produced in other tissues apart from thyroid.
FALSE.T4 only made in thyroid glans.
T4
thyroxine
Where is T3 made/
-thyroid
-deiodination of I4 in liver,brain.
Where does thyroid hormone usually stays within thryoid follicular cell?
Colloid droplet-gets ingested from apex of cell and travels twds base to get released in blood.
Check the iodide cycle
OK!!
Iodine
Essential for normal thryoid function.
Low iodine
In mountainous and inland regions
Sufficient/excess I2
Costal regions
Recommended daily intake of iodine in adults
150g
Iodine daily intake is high in
Pregnant women.200-250g
Dietary sources of Iodine
Bread,salt,medical products(cough syrups,vitamins,antiseptics)
Heart drug having large amt of Iodine in it.
Amiodarone
Iodine gets reduced before absorption to
Iodide
Principal site of I2 absorption
Small intestine
Is absorption virtually complete?
Yes
Plasma conc. of inorganic Iodide is
< 1 microgram/L
Iodide is removed from plasma by
thyroid and kidneys
Iodide also appears in
Breast milk and sweat.
Amt of Iodide perfusing thyroid being removed in each passage
20 %
Normal thyroid maintains a conc. of Iodide which is
20-50 times higher than that of plasma
Which protein responsible for transport and where is it found?
Sodium/Iodide transporter(NIS)
-in thyrocyte basal mb
What increases iodide transport activity?
Chronic TSH stimulation
NIS is a protein of
643 a.a with 13 mb spanning domains.
Carboxy terminus of NIS is
INSIDE cell( and amino is outside)
What first binds to transporter?
Na+ which forms a complex in presence of Iodide--->transfers 2Na+ and iodide inside cell.
Gene for NIS located on
chrm 19p
main cell inside thyroid gland
thyrocyte
Protein which transports iodine from cell to lumen
Pendrin-Cl-/I- transporter across thyroid apical mb.(genetic abno. leads to goitre)
Other transporter from cell to lumen
Apical Iodide Transporter(ATI)-passive iodide transport activity.
Check diagram of thyroid hormone synthesis
OK
Iodide oxidized by
Thyroid peroxidase(requires H2O2)
Iodide covalently bound to what in the exocytotic vesicles fused with apical cell mb.
Tyrosyl residues of thyroglobulin.
Thyroid peroxidase(TPO)
Protoporphyrin-IX heme protein uniquely expressed in thyroid.
What rapidly increases Thyroid peroxidase mRNA transcription?
TSH or cAMP
TPO synthetized where?
on polysomes
TPO undergoes glycosylation where?
Golgi apparatus.
With what is thyroid peroxidase packaged into exocytotic vesicles?
Thyroglobulin
TSH stimulate mvt of vesicles to
Apical mb.
TPO found in
mb-associated with microvilli.
C-terminal of TPO is
Hydrophobic
C-terminal of TPO is on
Apex of microvilli.
H202 produced from
NADPH thyroid oxidase
TPO is an enz. that helps to
bind Iodine onto tyrosine.
Iodine and tyrosine have
Separate binding sites on enzyme.(each oxidised by loss of 1 electron)
Iodine and tyrosine combine to form
Iodotyrosine
What is the most abundant protein in the thyroid?
Thyroglobulin
Main function of thyroglobulin(TG) is
Provide peptide backbone for synthesis and storage of thyroid hormones.
Each TG molecule contains abt
140 tyrosyl residues
TG coded by
gene on chrm 8 & consists of 2 identical subunits bound together by ionic and disulphide bonds
How long is iodinated TG stored for in colloid?
hours to 100 days
How is TG resorbed into the cell?
micropinocytosis
TG is degraded into iodothyronines in
Lysosomes
TG measurement is relevant
In follow up of pts with thyroid cancer.If TG present in circulation,recurrence of cancer.
How is iodothyronine formed?
Iodinated hydroxyphenol group of 1 iodotyrosine residue to phenolic hyroxyl of another
TPO is also responsible for
Coupling
2 diodotyrosine residues couple within 1 TG molecule to give
T4
1 monoiodotyrosine and 1 diodotyrosine couple within 1 TG to give
T3
In what form is thyroglobulin resorbed in follicular cell?
Colloid droplets
TG hydrolyzed to
T4 and T3---> ECF then circulation
Most thyroid hormones made in
Colloid
Deiodination of T4 to T3 leads to
Increased biological activity
T4
-produced at 80-100ug/day
-degraded at 10%/day
-80% deiodinated(40% to T3,40% to rT3)
T3
triiodothyronine
T3
-80% produced by extrathyroidal deiodination of T4 and rest by thyroid.
-production rate 30-40 ug/day
rT3
all produced by extrathyroidal deiodination of T4(30-40 ug/day)
What are the serum binding pz for thyroid hormones?
-Thyroxine Binding globulin(TBG)
-Transthyrethrin
-Albumin
-Lipopz
TBG binds
75 % of circulating T4(also binds T3/rT3)
Fraction of TBG in serum containing T4
1/3
TBG synthetized where?
Liver
Increased estrogen levels
Increase TBG
Androgens
Decrease TBG
What determines biological activity?
FREE T4 and T3
What delays hypothyroidism if thyroid secretion ceases?
T4 stored in serum.
Thyroxine(T4)
-75% bound to TBG
-10% bound to TTR
-12% to albumin
-3% to lipopz
-0.03 % free in serum(10-26 pmol/L)
T3
-80% bound to TBG
-5% bound to TTR
-15% to albumin and lipopz
-0.3% free(3-6pmol/L)
Wolff-Chaikoff effect is
Inhibition of organification of iodide with sudden exposure to excess serum Iodide-decreased hormone biosynthesis.(resumes in 2-4 wks)
T4/T3 can dissociate from binding pz instantaneously.
True
T4/T3 enter cells by
processes that energy dependent or Na+ dep.
Transporters for cellular uptake of thyroid hormones?
-monocarboxylate transporter(MCT8)
-OATP1
MCT8
-gene on chrm Xq13.2
-mutations of MCT8 assoc. with psychomotor retardation/ elevated T3 levels.
-MCT8 role in T3 supply to neurons.
How many enz. catalyze deiodination?
3.
-D1 in liver,kidneys and thyroid
-D2 in brain,pituitary,muscle,heart.
-D3 in brain,placenta,foetal tissues.
Clinical thyroid disorders assoc. with
Iodine metabolism and thyroid hormone production.
Iodine deficieny
Global problem where soil is deprived of Iodine-assoc. with cretinism.
Australia is
Deficient in Iodine
Myxedematous Endemic Cretinism:
-Dwarfism
-Retarded sexual dev.
-Puffy features
-Dry skin and hair
-Severe mental retardation
Hashimoto's thyroiditis clinical features:-
-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
In Hashimoto's,
T4 is low and TSH high (high levels of Thryoid peroxidase Ab and thyroglobulin Ab present)
Commonest cause of Hypothyroidism is
Hashimoto's
What happens in Hashimotos?
-Gradual thyroid failure,goitre or both due to autoimmune mediated destruction of thyroid follicular cells.
What kind of cells infiltrate thyroid gland in Hashimotos?
Lymphocytes
T4/T3 regulation via negative feedback is by acting on
Hypothalamus,releasing TRH if low T4/T3---> act on pituitary to release TSH.
Lab. dx of Hypothyroidism:-
-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)
Useful tests to dx hypothyroidism :-
-thyroid Ab
-thyroglobulin
-thyroid peroxidase.
Tx of hypothyroidism in pts < 60 y.o and in absence of ischemic HD :-
Thyroxine 50-100g orally daily with increase over 3-6 months to 100-200 ug/day