iodine and the thyroid: how the thyroid uniquely adapts to its environment to achieve normal somatic...

Iodine and the Thyroid: Iodine and the Thyroid: How the thyroid uniquely adapts How the thyroid uniquely adapts

to its environment to achieve to its environment to achieve normal somatic and neurological normal somatic and neurological

development.development.International Society for Enzymology Annual International Society for Enzymology Annual

Conference 2016: Conference 2016: "An International Laboratory Medicine and "An International Laboratory Medicine and

Pathobiology Conference“ Syros GreecePathobiology Conference“ Syros Greece

Professor Steven C. BoyagesProfessor Steven C. BoyagesWestmead HospitalWestmead Hospital

The university of Sydney, AustraliaThe university of Sydney, Australia

Nutrition Related DisordersNutrition Related Disorders

MicronutritionMicronutritionUndernutrition PCMUndernutrition PCM

Minerals and VitaminsMinerals and VitaminsFolic AcidFolic Acid

Vitamin D deficiencyVitamin D deficiencyVitamin A deficiencyVitamin A deficiency

Fe deficiencyFe deficiencySelenium deficiencySelenium deficiency

Iodine deficiencyIodine deficiency

MacronutritionMacronutritionObesityObesity

HyperlipidemiaHyperlipidemiaInsulin ResistanceInsulin Resistance

DiabetesDiabetesAlcoholAlcohol

Iodine Deficiency DisordersIodine Deficiency DisordersSIGNIFICANCESIGNIFICANCE

One of the commonest nutritional disordersOne of the commonest nutritional disorders Over 1 billion people live in deficient Over 1 billion people live in deficient

environmentsenvironments Affects primarily the thyroid but secondarily Affects primarily the thyroid but secondarily

may impact on brain developmentmay impact on brain development Most preventable cause of mental Most preventable cause of mental disabilitydisability Not limited to developing countriesNot limited to developing countries Principles of food fortification to populationsPrinciples of food fortification to populations Structural basis of scientific thinking (Kuhn)Structural basis of scientific thinking (Kuhn)

OutlineOutline Nutritional DisordersNutritional Disorders Principles of thyroid physiologyPrinciples of thyroid physiology Iodine physiologyIodine physiology What is a normal iodine level?What is a normal iodine level? How do we adapt to iodine deficiency?How do we adapt to iodine deficiency? Iodine Deficiency DisordersIodine Deficiency Disorders Are we at risk?Are we at risk?

Thyroid PhysiololgyThyroid Physiololgy

Thyroid Function TestsThyroid Function Tests TSH, direct measure of thyroid TSH, direct measure of thyroid

hormone actionhormone action– Different types of thyroid hormone Different types of thyroid hormone

receptorsreceptors Free T4, estimatesFree T4, estimates Free T3, estimatesFree T3, estimates

Iodine is essential for normal Iodine is essential for normal thyroid hormone synthesisthyroid hormone synthesis

Na Iodide TransporterNa Iodide Transporter

What is normal intake?What is normal intake?Too little and Too much can be Too little and Too much can be

a problema problem

Recommended intakesRecommended intakes

The American Thyroid Association has recently recommended that all women receive 150 µg iodine supplements above their dietary intake during pregnancy and lactation, and that the iodine content in all prenatal vitamins should be standardized at 150 µg

Sources of iodineSources of iodine SaltSalt MilkMilk BreadBread Other foods, eg kelp, seaweed, laverOther foods, eg kelp, seaweed, laver MedicationsMedications

Sources of iodineSources of iodine Dietary iodine Daily intake (µg)Dietary iodine Daily intake (µg) Dairy products Dairy products 5252 GrainsGrains 7878 Meat Meat 3131 Mixed dishes Mixed dishes 2626 Vegetables Vegetables 2020 Desserts Desserts 2020 Eggs Eggs 1010 Iodized salt Iodized salt 380380 Other iodine sourcesOther iodine sources(µg)(µg) Vitamin/mineral prep (per tablet) Vitamin/mineral prep (per tablet) 150150 Amiodarone (per tablet) Amiodarone (per tablet) 75,00075,000 Povidone iodine (per mL) Povidone iodine (per mL) 10,00010,000 Ipodate (per capsule) Ipodate (per capsule) 308,000308,000

Endemic GoitreEndemic Goitre

Adaptation to iodine deficiencyAdaptation to iodine deficiency

OutlineOutline Nutritional DisordersNutritional Disorders Principles of thyroid physiologyPrinciples of thyroid physiology Iodine physiologyIodine physiology What is a normal iodine level?What is a normal iodine level? How do we adapt to iodine deficiency?How do we adapt to iodine deficiency? Iodine Deficiency DisordersIodine Deficiency Disorders

– Iodine and brain damageIodine and brain damage Are we at risk?Are we at risk?

Iodine Deficiency DisordersIodine Deficiency Disorders

Iodine Deficiency Disorders (IDD) refers to all of the ill effects of iodine deficiency in a population that can be prevented by ensuring that the population has an adequate intake of iodine

Iodine DeficiencyIodine Deficiency Iodine deficiency at critical stages

during pregnancy and early childhood results in impaired development of the brain and consequently in impaired mental function.

Model of prenatal thyroid hormone Model of prenatal thyroid hormone action on fetal brain developmentaction on fetal brain development

Early recognition of goitre with Early recognition of goitre with impaired mental abilityimpaired mental ability

"Hence while travelling in a "Hence while travelling in a certain region in the County certain region in the County Tyrol, under the jurisdiction of Tyrol, under the jurisdiction of the Bishop of Gurk, I was the Bishop of Gurk, I was astonished at the very large astonished at the very large number of number of madmen, fools and madmen, fools and doltsdolts; but when I considered ; but when I considered the frigidity and the humidity the frigidity and the humidity of the air, and also perceived of the air, and also perceived the crudity of the waters from the crudity of the waters from the very frequent occurrence the very frequent occurrence of of goitregoitre... all astonishment ... all astonishment ceased entirely." ceased entirely."

EUSTACHIUS RUDIUS, A EUSTACHIUS RUDIUS, A PHYSICIAN FROM UTRECHTPHYSICIAN FROM UTRECHT

(1551-1611)(1551-1611)

Endemic CretinismEndemic Cretinism Occurs in areas of Occurs in areas of

severe iodine severe iodine deficiency and deficiency and almost universal almost universal endemic goitreendemic goitre

Geographic Geographic clusteringclustering

Two predominant Two predominant clinical phenotypesclinical phenotypes

Iodine Deficiency DisordersIodine Deficiency Disorders ThyroidThyroid Mild to ModerateMild to Moderate

– Thyroid autonomyThyroid autonomy– Nodular thyroid Nodular thyroid

diseasedisease– GoitreGoitre– Thyroid MalignancyThyroid Malignancy

BrainBrain SevereSevere

– Endemic cretinismEndemic cretinism– DeafnessDeafness– Subclinical deafnessSubclinical deafness– intellectual intellectual

disabilitydisability– ?Attention deficits?Attention deficits– ? Colour perception ? Colour perception

deficitsdeficitsIodine Deficiency Disorders (IDD)Iodine Deficiency Disorders (IDD)1000 million people at risk for 1000 million people at risk for

the development of IDDthe development of IDD

Mechanism of damageMechanism of damage Thyroid hormone is essential for normal Thyroid hormone is essential for normal

brain gene expressionbrain gene expression– NeurogenesisNeurogenesis– MyelinationMyelination– MigrationMigration– DifferentiationDifferentiation

Classical sensitive window in the Classical sensitive window in the developing braindeveloping brain

Timing and Region dependent gradient of Timing and Region dependent gradient of sensitivitysensitivity

Brain Damage: Shift in the IQ Brain Damage: Shift in the IQ distribution to the leftdistribution to the left

The neurological sequelae are not an all or The neurological sequelae are not an all or none phenomenonnone phenomenon

The population distribution of cognitive The population distribution of cognitive function shows a marked shift to the left function shows a marked shift to the left towards lower IQ scorestowards lower IQ scores

10 to 15 IQ points10 to 15 IQ points

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70-7

9

80-8

9

90-9

9

100-

109

110-

119

120-

129

130-

139

140-

149

0

10

20

Iodine deficient (pre-prophylaxis)

Rural control (old)

City controls

City controls

Intelligence Quotient (IQ)

Frequency (%)

BEFORE IODISEDSALT PROPHYLAXIS

Timing of insultTiming of insultTiming of Timing of

insultinsultPrenatalPrenatal PostnatalPostnatal

TargetTarget Fetal brainFetal brainFetal thyroidFetal thyroid

Maternal Maternal thyroidthyroid

Child and Child and AdultAdult

ThyroidThyroid

OutcomeOutcome Endemic Endemic cretinismcretinism

Impaired IQImpaired IQ

Endemic Endemic GoitreGoitreShort Short

StatureStature

Iodine Deficiency in Iodine Deficiency in AustraliaAustralia

TasmaniaTasmaniaUrine Iodine DistributionUrine Iodine Distribution

Median UIE 84mcg/l

Thyroid Size Using Thyroid Thyroid Size Using Thyroid Ultrasound: Boys and GirlsUltrasound: Boys and Girls

24.6% 20.7%

Other Australian StatesOther Australian States

We need a new marker to We need a new marker to assess iodine statusassess iodine status

Urine iodineUrine iodine Serum TSHSerum TSH Thyroid hormonesThyroid hormones ThyroglobulinThyroglobulin Protein Bound Protein Bound

IodineIodine Iodinated Iodinated

thyroglobulinthyroglobulin Thyroid UltrasoundThyroid Ultrasound

Needs to be stable, Needs to be stable, reproducible and reproducible and reflect iodine reflect iodine status over weeks status over weeks to months, not to months, not daysdays

CONCLUSIONCONCLUSIONThyroid hormone is essential for Thyroid hormone is essential for

normal somatic and neurological normal somatic and neurological development. development.

Iodine deficiency leads to thyroid Iodine deficiency leads to thyroid hormone deficiency at critical periods hormone deficiency at critical periods of brain development that leads to of brain development that leads to irreversible neurological damage.irreversible neurological damage.

Prevention of iodine deficiency is Prevention of iodine deficiency is essentialessential

AcknowledgementsAcknowledgements AustraliaAustralia

– CJ EastmanCJ Eastman– JP HalpernJP Halpern– John K CollinsJohn K Collins– Li MuLi Mu

ChinaChina IndonesiaIndonesia The NetherlandsThe Netherlands

– Hemmo DrexhageHemmo Drexhage USA, AtlantaUSA, Atlanta

– GF MaberlyGF Maberly Italy, PisaItaly, Pisa

– Alessandro AntonelliAlessandro Antonelli

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