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IDD FestivalMedical Publication Editors Society24-25 May-2010Tehran-IR-Iran

Dr.S. Zahedi, PhD,Professor of Endocrine Physiology, Endocrine Research Center, Research Institute for Endocrine Sciences Shaheed Beheshti University of Medical Sciences, Tehran-IR-Iran zahedi@endocrine.ac.ir

Iodine and Thyroid Physiology

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Iodine

• Atomic Number: 53 • Symbol: I • Atomic Weight: 126.90447 • Discovery: Bernard Courtois 1811 (France)• Melting point :of 113.5°C• Slightly soluble in water

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Evaporative salts .........................avg. 10 ppb (Roeber)Ocean ................................................... 50 ppb Igneous rocks ...............................avg. 100 ppb (R. Fuge)Average Crustal Content ................... 300 ppb (Manson)Sedimentary rocks .......................avg. 1800 ppb (Itkina, Lygalova)Soils ............................................avg. 4800 ppb (Goudge, 260,000 + soil samples)

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Sources

• Iodine is primarily retrieved from underground brines (water with many dissolved salts and ions) that are associated with natural gas and oil deposits.

• It is also retrieved as a by-product with nitrate deposits in caliche deposits. Chile’s production of iodine is from this source.

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• Seawater contains 50 ppm (parts per million) iodine which means that there are approximately 76 billion pounds of iodine in the world’s oceans.

• Iodine was first discovered in seaweed. • Dried seaweeds, particularly those of the

Liminaria family, contain as much as 0.45% iodine.

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• Seaweed was a major source of iodine before 1959.

• Seaweed is a significant source for iodine in the diets of many people around the world.

• Production from caliche is presently the most economical of the options listed here

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• "The basic source of iodine in soils is iodine of the atmosphere.“

• " The ocean is the reservoir from which all of the iodine of the atmosphere is drawn"

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• Seafood – Cod – Sea bass – Haddock – Perch – Kelp

• Dairy products • Plants grown in soil rich in iodine

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In each 100 gr• Iodized Salt 3000 mcg• Cereals and Breads 10-11 mcg• Meat 26-27 mcg• Vegetables 32-33 mcg• Fruits 25-70 mcg• Haddock Almost 300 mcg• Malt bread29-30 mcg• Jaffa cakes More than 32 mcg• Cod More than 90 mcg• Boiled Egg 1 egg 23.76 mcg• Mayonnaise 35-36 mcg

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• The highest iodine content is found in brown algae, with dry kelp ranging from 1500-8000 ppm (parts per million) and dry rockweed (Fucus) from 500-1000 ppm.

• In most instances, red and green algae have lower contents, about 100-300 ppm in dried seaweeds, but remain high in comparison to any land plants.

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• Daily adult requirements, currently recommended at 150 µg/day, could be covered by very small quantities of seaweed.

• Just one gram of dried brown algae provides from 500-8,000 µg of iodine

• Even the green and red algae (such as the purple nori that is used in Japanese cuisine) provides 100-300 µg in a single gram.

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Iodine absorption

• Oral. Iodine appears to be inactivated by combination with gastrointestinal contents. Absorption is poor due to rapid conversion of iodine to iodide. (Reynolds, 1989; Gilman et al., 1990).

• "Inhalation. Iodine is absorbed from the lungs, converted to iodide in the body, (ILO 1971). Pulmonary absorption of vapour may result in systemic poisoning (Gosselin et al., 1984).

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Absorption…….

"Dermal. Only very small quantities of iodine are absorbed through an intact skin, (Reynolds, 1989).

• Iodine can be absorbed by wounds and abrasions. • Enhanced absorption occurs through denuded skin,

decubitus ulcers, mucosal surfaces with high absorptive capacity , or large areas of intact skin, (Dela Cruz et al., 1987; Vorherr et al., 1989; Prager & Gardner 1979; Cosman et al., 1988).

• "Eye. Iodine can be absorbed when applied on the eye, (Geisthoevel, 1984).

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Iodine secretion

• Iodine is secreted in saliva, other gastrointestinal fluids, and breakdown of iodine from hormones is reabsorbed in the digestive tract

• Intestinal parasitic infestations interfere with iodine absorption

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Iodine Absorption

• The question of where and how dietary I is absorbed in the gastrointestinal tract has long been of major interest.

• Reports on the absorption of I in the intestine appeared as early as 1912 .

• In the 1950s, some authors suggested that I might be both absorbed from and secreted to the intestinal lumen.

• Passive or simple diffusion of iodide from the intestinal lumen to the bloodstream was believed to be the mechanism in iodide absorption.

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Iodine transport

• Active I- accumulation in the thyroid is mediated by the Na+/ I- symporter (NIS), a plasma membrane glycoprotein

• Using as its driving force the Na+ gradient generated by the Na+_-K+_-ATPase, NIS couples the inward movement of Na+ in favor of its concentration gradient to the inward movement of I- against its electrochemical gradient. Characteristic hallmarks of

• Characteristic hallmarks of NIS are its Na dependence

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• NIS mediates I uptake in several tissues besides the thyroid, including :

• Lactating mammary gland, • Gastric mucosa,• & salivary glands• It appears that Na+/ I- symporter is present in

GI tract small intestine)

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Pyramidal lobe

About 20 grIn women> menComposed of follicles

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Originate from endoderm of primitive pharynx

Originate from neural crest

Innervation:SympatheticParasympatheticPeptidergic VIP NPY Sub. P Galanin

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Thyroid Cells© Tight Junctions© Adherent junctions© Desmosome junctions===================® Gap junctions® Polarity

Apical

Microvilli Ability to form Pseudopods Peroxidase Aminopeptidase H2O2 generating capacity --------------------------------------- polarity is also indicated by organelles

Besolateral K-Na ATPase TSH receptorsNa-I Symporter

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• Concentration of Iodine• Synthesis of Tg• Synthesis of TPO• H2O2 generation• Re-absorption of iodinated Tg• Degradation of iodinated Tg• ============================• Hormone synthesis and secretion

Function of Thyroid Cells:

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Pendrin

Passive diffusion can restore thyroid functionBut 50-100 fold iodine intake is nec.

-5-mv

Against gradient of charge and concentration

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THYROGLOBULIN

o Code for synthesis in human Ch. 8, rat Ch. 7o 2 subunit 330 KDa eacho Carbohydrate 8-10%, Mannose, Galactose, N-

acetylglucosamine, Sialic Acid, Fucoseo Idoinated form

o Dimmero .2-1% iodine

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H2O2 production

NADPH Oxidase NADPH Oxidase

NADPH NADPHNADP+ NADP+

O2 2O2-

H2O2

H2O2

O2 H2O2

Ca2+

Electron acceptor

Superoxide dismotase (SOD)

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Hormone synthesis

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Thyroid Hormone Secretion

• Pinocytosis, Macro( up to 3 um), Micro (100-200nm)• Colloid droplets, receptor mediated, low affinity• Lysosomes (0.1-1 um) containing hydrolytic enz( proteolytic).

Active at Acidic pH <6» Aspartic proteinase, CathepsinD» 2 Cystein proteinase Cath. L & B

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r= 1

r=.5T4/

T3

efflu

ent

T4/T3 in thyroid

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Thyroxine Binding Globulin• 54 KD• Acidic Glycoprotein (20%) 1 binding site• Asso. Constant 1*1010 (T4)• Asso. Constant 1*109 (T3)• X chromosome• In Euthyroid subjects 1/3 is occupied• Fully saturated 20 ug/dL• Half life ~ 5 days• Est incraese HL due to increase of the number of sialic acid

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Thyroxine Binding Pre albumin( Transthyretin TTR)

• 55 KD Tetramer• Each 127 AA• 1 T4 per mol• Chromosome 18• Half life ~ 2 days• It forma a complex with Retinol Binding

Protein: Stabilize the protein

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Albumin

• 66.5 KD Tetramer• 585 AA• Several binding site but only 1 has high affinity• Chromosome 4• Half life ~ 15 days

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Receptors

• T3 receptors are nuclear proteins of 400–500 amino acids containing several functional domains, especially the ligand and the DNA binding domains.

• There are two receptor genes, designated TRa and TRb, located in different chromosomes.• Types α1 , 2, & 3 Gen located at ch. 17• Types β1 , 2, &3Gen located at ch. 3

• They encode nine protein products that arise by alternative splicing and differential promoter usage.

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Thyroid hormone

• Metabolic• Thermogenic• Carbohydrate metabolism• Protein metabolism• Fat metabolism

• Effect on organs• Cardiovascular system• Respiratory system• Central system

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Thyroid hormones Metabolic effects

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Thyroid hormones Metabolic effects

• Heat production» Increased metabolism» Increased Na-K ATPase activity» Increased synthesis of uncoupling protein in adipose

tissue

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Thyroid hormones Metabolic effects

• Carbohydrate Met.» Increased glucose consumption» Increased glucose absorption» Increased insulin release

• Protein Met.» Increased anabolism» Increased catabolism» Net effect in hyoerthyroidism NNB

• Lipid Met.» Increased anabolism» Increased catabolism» Net effect = catabolism

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Ventromedial NSuprachiasmatic NPreoptic AreaParaventricular N

TRH5HT HistaminCathecolaminesOpioidsVas+

DopamineGlucocorticoidsTNF& IL-1bT3Somatostatin_

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