endokrin_thyroid_2011.pptx

7/28/2019 Endokrin_Thyroid_2011.pptx

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Department of Physiology Diponegoro University Faculty of Medicine

The Endocrine System

Thyroid Gland


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Thyroid Gland


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Histologic Section of Normal Thyroid

colloidFollicular cells

C cells


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Thyroid hormonethe bodys majormetabolic hormone

Consists of two closely related iodine-

containing compounds T4 thyroxine; has two tyrosine molecules plus

four bound iodine atoms

T3 triiodothyronine; has two tyrosines with three

bound iodine atoms

Calcitonin

Thyroid Hormones


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OH

O

I I

CH2

I I

OH

O

I

CH2

I I

NH2CHCOOH NH2CHCOOH

Thyroxine (T4) Triiodothyronine (T3)

Thyroid Hormones


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Thyroglobulin is synthesized and discharged into the

lumen Iodides (I) are actively taken into the cell, oxidized

to iodine (I2), and released into the lumen

Iodine attaches to tyrosine, mediated by peroxidaseenzymes, forming T1 (monoiodotyrosine, or MIT),and T2 (diiodotyrosine, or DIT)

Iodinated tyrosines link together to form T3 and T4

Colloid is then endocytosed and combined with alysosome, where T3 and T4 are cleaved and diffuseinto the bloodstream

Synthesis of T3 and T4


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I + tyrosine monoiodotyrosine (MIT)

MIT + I diiodotyrosine (DIT)

DIT + DIT thyroxine (T4)

DIT + MIT triiodothyronine (T3)

hormones still attached to thyroglobulin


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Synthesis of Thyroid Hormone


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T4 and T3 bind to thyroxine-binding globulins(TBGs) produced by the liver

Both bind to target receptors, but T3 is ten timesmore active than T4

T3 also being produced in the peripheral tissuesby deiodination of T 4 (~ 80% of T 3 )

reverse T 3 (rT 3 ) is inactive Mechanisms of activity are similar to steroids

Regulation is by negative feedback Hypothalamic thyrotropin-releasing hormone

(TRH) can overcome the negative feedback

Transport and Regulation of TH

d


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T3 and T4

Bound to carrier proteins in the plasma

Mainly thyroxine (t4) is released

- thyroid binding globulin (TBG)

- albumin (10%)

- transthyretin (20%)

- T4:T3 ratio = 25

- T3 is formed by the deiodination of T4


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Iodine metabolisme The minimum adult daily requirement to maintain

thyroid function 100-150 g The thyroid secretes 80 g of I- per day as T3 &

T4, of which 60 g is metabolised in the liver with

release of I- into the ECF

The total I- added to the plasma per day : 500 g - average dietary intake

60 g - from the liver metabolism of T3

& T4

40 g - diffusion from the thyroid to theECF


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About 600 g of iodide is distributed throughoutthe ECF daily:

Thyroid takes up ~ 20% or ~ 120 g/day

Remaining 80% is taken up by the kidney and

excreted in the urine

Iodine metabolisme


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Iodine balance

f h d ll l


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Action of Thyroid Hormone in Cell Nuclei

The active form of thyroid hormone, triiodothyronine (T3), is produced by deiodination of thyroxine

(T4) by the enzymes T4 5'-deiodinase (5'-D) types I and II1. Type I T4 5'-deiodinase is found

predominantly in the liver and kidneys; its action is responsible for the production of two thirds of thetotal T3 in the body. Type II T4 5'-deiodinase is responsible for most of the T3 found in the pituitary,

the brain, and brown fat. T3 enters the cell or is produced locally and then transported into the

nucleus. Transcriptionally active forms of thyroid hormone receptors (TR) include monomers,

homodimers, and heterodimers with nuclear protein partners, such as the retinoid X receptor (RXR).

The T3-receptor complex interacts with specific sequences in DNA regulatory regions and modifies

gene expression. T3 causes both increases and decreases in gene expression and may also influence

the stability of messenger RNA (mRNA). 9-cis RA denotes 9-cis-retinoic acid, the ligand for RXR


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Physiological Actions of Thyroid Hormones


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Physiological Actions of Thyroid Hormones

effects of T3 and T4 are nearly identical except for latency and potency

essential for growth in childhood

various metabolic effects:

- increase breakdown of carbohydrates

- increase breakdown of lipids- determine metabolic rate

- level of heat production

Effects on Organ Systems


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Effects on Organ Systems

HEART increases rate, decreases force

VASCULAR vasodilation

GI increased motility and absorption

SKELETAL increased bone turnover

NEUROMUSCULAR hyperactivity, increased muscle contraction


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TH is concerned with:

Glucose oxidation

Increasing metabolic rate

Heat production

TH plays a role in:

Maintaining blood pressure

Regulating tissue growth

Developing skeletal and nervous systems

Maturation and reproductive capabilities

Effects of Thyroid Hormone

Regulation of Thyroid Hormone Release


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Regulation of Thyroid Hormone Release

Production and secretion of T3 and T4 is controlled by thyroid stimulating hormone

(TSH) released from the anterior pituitary

increasing plasma TSH causes:

TSH release under feedback control

release of formed T3 and T4

increased rate of iodide uptake

increased rate of synthesis

increased size and number of follicles

Th id H C t l P th


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Thyroid Hormone Control Pathways

Thyroid hormone pathway

Additional Mechanism of T3/T4 Release


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Additional Mechanism of T3/T4 Release

Cold exposure:

a decrease in temperature acts via the hypothalamic

thermoregulatory centre to increase release of TRH

an increase in temperature has the reverse effect


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TPOAb= Thyroid Peroxidase Antibody


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Department of Physiology Diponegoro University Faculty of Medicine

Increase in thyroid binding globulin due to increase in

estrogen (stimulation of hepatic production and

decreased degradation) Increase in total T4 and T3

Increase in GFR leads to increase in renal iodine

clearance

HCG has similar properties to TSH therefore hasintrinsic thyroid stimulating activity

Increase FT4 and FT3 levels during first trimester


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TSH upper reference limit (2.53.0 mIU/L). Below 2.5 mIU/L in the first trimester

and preconception and 3.0 mIU/L in the second and third trimesters

The range of normal serum total T4 changes during pregnancy

Rapid increases in TBG levels T4 increase

Total T4 level 50% higher than non-pregnant levels (512 g/dL or 50150

nmol/dL)

In the second and third trimester multiply this range by 1.5-fold.


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Thyroid Dysfunctions


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Thyroid Dysfunctions

Hypothyroidism


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Hypothyroidism

Hyperthyroidism


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Hyperthyroidism


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Cretinism


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Cretinism

Congenital absence of T3 and T4 or chronic iodine

deficiency during childhood

- Retarded growth

- Sluggish movements

- Mental deficiencies- Big tongue

Adult hypothyroidism


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Adult hypothyroidism

- Low rate of

metabolism andlethargy

- Decreased body temp

- Decreased heart rate

- Outer skin becomes

scaly

- Myxedema non

pitting edema due to

swelling of

subcutaneuous

connective tissues

Myxedema


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Myxedema


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Hyperthyroidsm

Hyperthyroidism: the thyroid becomes over-active and

produces too much of its hormones thyrotoxicosis

Hyperthyroidism over-activity of the organs resulting

in symptoms such as sweating, feeling hot, rapid

heartbeats, weight loss, and sometimes eye problems.

Thyroid storm: the levels of thyroid hormones become

very high in a patient who has hyperthyroidism.

One major sign of thyroid storm is a marked elevation ofbody temperature 41o C. It is a life-threatening

emergency.

Adult hyperthyroidism


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Adult hyperthyroidism -Graves disease

Tall stature

Hyperactive

High rate of

metabolism High body

temperature

High heart rate


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Exophthalmus


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Exophthalmus

edematous swelling at the rear of eye socket


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Goiter


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swelling in neck due to thyroid

hypertrophy

both hypo- and hyperthyroidism

endokrin_thyroid_2011.pptx

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