This presentation describes how the thyroid actively traps iodine, a rare micronutrient, to produce thyroid hormones. Iodine is important for normal fetal and adult development.

1. Iodine and the Thyroid:Iodine and the Thyroid:
How the thyroid uniquely adapts toHow the thyroid uniquely adapts to
its environment to achieve normalits environment to achieve normal
somatic and neurologicalsomatic and neurological
development.development.
International Society for Enzymology AnnualInternational 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. Boyages
Westmead HospitalWestmead Hospital
The university of Sydney, AustraliaThe university of Sydney, Australia

2. Nutrition Related DisordersNutrition Related Disorders
MicronutritionMicronutrition
Undernutrition PCMUndernutrition PCM
Minerals and VitaminsMinerals and Vitamins
Folic AcidFolic Acid
Vitamin D deficiencyVitamin D deficiency
Vitamin A deficiencyVitamin A deficiency
Fe deficiencyFe deficiency
Selenium deficiencySelenium deficiency
Iodine deficiencyIodine deficiency
MicronutritionMicronutrition
Undernutrition PCMUndernutrition PCM
Minerals and VitaminsMinerals and Vitamins
Folic AcidFolic Acid
Vitamin D deficiencyVitamin D deficiency
Vitamin A deficiencyVitamin A deficiency
Fe deficiencyFe deficiency
Selenium deficiencySelenium deficiency
Iodine deficiencyIodine deficiency
MacronutritionMacronutrition
ObesityObesity
HyperlipidemiaHyperlipidemia
Insulin ResistanceInsulin Resistance
DiabetesDiabetes
AlcoholAlcohol
MacronutritionMacronutrition
ObesityObesity
HyperlipidemiaHyperlipidemia
Insulin ResistanceInsulin Resistance
DiabetesDiabetes
AlcoholAlcohol

4. Iodine Deficiency DisordersIodine Deficiency Disorders
SIGNIFICANCESIGNIFICANCE
 One of the commonest nutritional disordersOne of the commonest nutritional disorders
 Over 1 billion people live in deficientOver 1 billion people live in deficient
environmentsenvironments
 Affects primarily the thyroid but secondarilyAffects primarily the thyroid but secondarily
may impact on brain developmentmay impact on brain development
 Most preventable cause of mentalMost 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)

5. 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?

6. Thyroid PhysiololgyThyroid Physiololgy

7. Thyroid Function TestsThyroid Function Tests
 TSH, direct measure of thyroidTSH, direct measure of thyroid
hormone actionhormone action
– Different types of thyroid hormoneDifferent types of thyroid hormone
receptorsreceptors
 Free T4, estimatesFree T4, estimates
 Free T3, estimatesFree T3, estimates

8. Iodine is essential for normalIodine is essential for normal
thyroid hormone synthesisthyroid hormone synthesis

9. Na Iodide TransporterNa Iodide Transporter

10. 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?

11. What is normal intake?What is normal intake?
Too little and Too much can be aToo little and Too much can be a
problemproblem

12. 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

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

14. Sources of iodineSources of iodine
 Dietary iodine Daily intake (µg)Dietary iodine Daily intake (µg)
 Dairy productsDairy products 5252
 GrainsGrains 7878
 MeatMeat 3131
 Mixed dishesMixed dishes 2626
 VegetablesVegetables 2020
 DessertsDesserts 2020
 EggsEggs 1010
 Iodized saltIodized 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

15. 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?

17. Endemic GoitreEndemic Goitre

18. Adaptation to iodine deficiencyAdaptation to iodine deficiency

19. 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?

20. 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

21. 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 hormoneModel of prenatal thyroid hormone
action on fetal brain developmentaction on fetal brain development

22. Early recognition of goitre withEarly recognition of goitre with
impaired mental abilityimpaired mental ability
"Hence while travelling in a"Hence while travelling in a
certain region in the Countycertain region in the County
Tyrol, under the jurisdictionTyrol, under the jurisdiction
of the Bishop of Gurk, I wasof the Bishop of Gurk, I was
astonished at the very largeastonished at the very large
number ofnumber of madmen, fools andmadmen, fools and
doltsdolts; but when I considered; but when I considered
the frigidity and the humiditythe frigidity and the humidity
of the air, and also perceivedof the air, and also perceived
the crudity of the watersthe crudity of the waters
from the very frequentfrom the very frequent
occurrence ofoccurrence of goitregoitre... all... all
astonishment ceasedastonishment ceased
entirely."entirely."
 EUSTACHIUS RUDIUS, AEUSTACHIUS RUDIUS, A
PHYSICIAN FROM UTRECHTPHYSICIAN FROM UTRECHT
 (1551-1611)(1551-1611)

23. Endemic CretinismEndemic Cretinism
 Occurs in areas ofOccurs in areas of
severe iodinesevere iodine
deficiency anddeficiency and
almost universalalmost universal
endemic goitreendemic goitre
 GeographicGeographic
clusteringclustering
 Two predominantTwo predominant
clinical phenotypesclinical phenotypes

24. Iodine Deficiency DisordersIodine Deficiency Disorders
 ThyroidThyroid
 Mild to ModerateMild to Moderate
– Thyroid autonomyThyroid autonomy
– Nodular thyroidNodular thyroid
diseasedisease
– GoitreGoitre
– Thyroid MalignancyThyroid Malignancy
 BrainBrain
 SevereSevere
– Endemic cretinismEndemic cretinism
– DeafnessDeafness
– Subclinical deafnessSubclinical deafness
– intellectual disabilityintellectual disability
– ?Attention deficits?Attention deficits
– ? Colour perception? Colour perception
deficitsdeficits
Iodine Deficiency Disorders (IDD)Iodine Deficiency Disorders (IDD)
1000 million people at risk for the1000 million people at risk for the
development of IDDdevelopment of IDD

26. Mechanism of damageMechanism of damage
 Thyroid hormone is essential for normal brainThyroid hormone is essential for normal brain
gene expressiongene expression
– NeurogenesisNeurogenesis
– MyelinationMyelination
– MigrationMigration
– DifferentiationDifferentiation
 Classical sensitive window in the developingClassical sensitive window in the developing
brainbrain
 Timing and Region dependent gradient ofTiming and Region dependent gradient of
sensitivitysensitivity

27. Brain Damage: Shift in the IQBrain Damage: Shift in the IQ
distribution to the leftdistribution to the left
 The neurological sequelae are not an all orThe neurological sequelae are not an all or
none phenomenonnone phenomenon
 The population distribution of cognitiveThe population distribution of cognitive
function shows a marked shift to the leftfunction shows a marked shift to the left
towards lower IQ scorestowards lower IQ scores
 10 to 15 IQ points10 to 15 IQ points

28. 20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
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 IODISED
SALT PROPHYLAXIS

29. Timing of insultTiming of insult
Timing ofTiming of
insultinsult
PrenatalPrenatal PostnatalPostnatal
TargetTarget Fetal brainFetal brain
Fetal thyroidFetal thyroid
MaternalMaternal
thyroidthyroid
Child andChild and
AdultAdult
ThyroidThyroid
OutcomeOutcome EndemicEndemic
cretinismcretinism
Impaired IQImpaired IQ
EndemicEndemic
GoitreGoitre
ShortShort

30. Iodine Deficiency in AustraliaIodine Deficiency in Australia

31. TasmaniaTasmania
Urine Iodine DistributionUrine Iodine Distribution
Median UIE 84mcg/l

32. Thyroid Size Using ThyroidThyroid Size Using Thyroid
Ultrasound: Boys and GirlsUltrasound: Boys and Girls
24.6% 20.7%

33. Other Australian StatesOther Australian States

34. We need a new marker toWe need a new marker to
assess iodine statusassess iodine status
 Urine iodineUrine iodine
 Serum TSHSerum TSH
 Thyroid hormonesThyroid hormones
 ThyroglobulinThyroglobulin
 Protein Bound IodineProtein Bound Iodine
 IodinatedIodinated
thyroglobulinthyroglobulin
 Thyroid UltrasoundThyroid Ultrasound
 Needs to be stable,Needs to be stable,
reproducible andreproducible and
reflect iodine statusreflect iodine status
over weeks toover weeks to
months, not daysmonths, not days

36. CONCLUSIONCONCLUSION
 Thyroid hormone is essential for normalThyroid hormone is essential for normal
somatic and neurological development.somatic and neurological development.
 Iodine deficiency leads to thyroidIodine deficiency leads to thyroid
hormone deficiency at critical periods ofhormone deficiency at critical periods of
brain development that leads tobrain development that leads to
irreversible neurological damage.irreversible neurological damage.
 Prevention of iodine deficiency isPrevention of iodine deficiency is
essentialessential

37. 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