Iodine and the Brain September 9, 2005 Rajata Rajatanavin, M.D., F.A.C.E. Ramathibodi Hospital, Mahidol University, Bangkok

I OH NH 2 II OCH 2 CH COOH Triiodothyronine (T 3 ) OH I NH 2 I I I OCH 2 CH COOH Thyroxine (T 4 ) Thyroid Hormone

Actions of Thyroid Hormone Brain development and maturation Physical growth and development Energy expenditure Regulating function of multiple organs

012 wksbirth1 yr PHASE I Thyroxine-Dependent-Human Brain Development PHASE IIPHASE III Neuronal differentiation, Axonal outgrowth, Dendritic ontogeny, synaptosis, Cerebellar neurogenesis, Gliogenesis Myelinogenesis Cerebral neurogenesis & migration 012 wksbirth1 yr Maternal T 4 Fetal T 4 Neonatal T 4

No. of births No. of cretins Birth-prevalence rate of cretinism (per 1,000) Injection before conception Injection after conception Oil Saline Oil Saline Pharoah and Connolty, 1989

Clinical Manifestation of IDD Depends upon onset severity duration of iodine deficiency + other environmental factors

Adult -Multinodular goiter and its consequences In utero -Abortion -Endemic cretins Neonates -Stillbirths -Increased perinatal mortallty - congenital hypothyroidism Preschool age -Mental deficiency -Psychomotor defect School age -Goiter

Endemic Cognitive Deficiency in Sicily Study areas Prevalence Psychomotor of Goiter (%) Defect (%) IDD area A IDD area B Control area 9 4 Vermiglio F, 1990

Cretinism 1-10 % 5-30 % Some Brain Damage % loss of Energy due to Hypothyroidism IDD ICEBERG

The Consequences of IDD Cretinism Cognitive and psychomotor deficiency Hypothyroidism Childhood mortality Reproductive failure Goiter Socioeconomic retardation

Odds ratio Rajatanavin R et al, Thyroid 1997;7:599

Odds ratio Rajatanavin R et al, Thyroid 1997;7:599

Maternal UI (  g/L) r = p = n = 203

Maternal UI (  g/L) * P = (9) (5) (49)

Indicators of IDD - UIE Population IDD Status WHO, UNICEF, ICCIDD (2001 ) Median value Iodine Status <20 µ g/l Severe iodine deficiency Moderate iodine deficiency Mild iodine deficiency Ideal iodine intake * More than adequate intake (may pose risk of IIH)* > 300 Excessive iodine intake In populations with longstanding iodine deficiency and rapid improvement in iodine intake, median values above 200 µ g/l are not recommended. *IIH : iodine induced hyperthyroidism

Urinary iodine level in pregnant women after supplement with iodized oil capsule Suibnugarn et al, capsule 2 capsules no supplement (2003) Recommended range 

Serum TSH Level of Neonatal Cord Blood Dansai Bangkok n Median TSH (mU/L) 95%Cl (mU/L) Dansai Suibnukarn et al, 2003

Median of urinary iodine in pregnant women Median urine iodine level (µg/l) Department of Health, MOPH : 2004

Median of urinary iodine in pregnant women Median urine iodine level (µg/l) Department of Health, MOPH : 2004

Median of urinary iodine in pregnant women Median urine iodine level (µg/l) Department of Health, MOPH : 2004

Division of Nutrition Department of Health:MOPH 2004 N = 55 provinces Status of Iodine Nutrition in Thailand

number of provinces North - East CentralSouth Adequate iodine Inadequate iodine Excessive iodine Division of Nutrition Department of Health: MOPH 2004 N = 55 provinces

Recommended Daily Iodine Intake and Urinary Iodine Excretion Intake Urinary Excretion  g/d  g/L RecomExcessRecomExcess Pregnant 250 > > 300 Women 200 Breast 250 > * Feeding 0-2 years 90 > * Of age *Need More data WHO/UNICEF Technical Conference, Geneva, January 2005

number of provinces North - East CentralSouth Inadequate iodine Adequate iodine Excessive iodine Division of Nutrition Department of Health: MOPH 2004 N = 55 provinces

คะแนนเฉลี่ยและค่าเบี่ยงเบน มาตรฐานของระดับเชาวน์ปัญญาเด็ก วัยเรียน การศึกษา ( ปี พ. ศ.) กรุงเ ทพฯ ภาค กลาง ภาค เหนือ ภาค อีสา น ภาคใ ต้ รวมทั้ ง ประเ ทศ การสำรวจ ภาวะ สุขภาพ ครั้งที่ 2 ( ) 96.5 (+13.7) 92.3 (+13.2) 87.9 (+15.9) 89.7 (+14.6) 94.7 (+14.5) 91.9 (+14.8) การศึกษา ครั้งนี้ (2545 ) 94.6 (+14.2) 88.8 (+12.0) 84.2 (+10.7) 85.9 (+11.1) 88.1 (+12.9) 88.0 (+12.6) นิชรา เรืองดารกานนท์ พัฒนาการและเชาวน์ปัญญาของ เด็กไทย, 2547

รายการ SD X SD <.001 X คะแนน IQ test Full IQ Verbal IO Performance IQ น้อย n = 100 รุนแ รง n = 100 ระดับการขาดสาร ไอโอดีนในพื้นที่ p Chavala Dhendhanoo, 1999

รายการ SD X SD <.001 X คะแนน subtest ของ IQ test Information Comprehension Arithmetic Similarity Digit Span Picture Completion Picture Arrangement Block Design Object Assembly Coding น้อย n = 100 รุนแรง n = 100 ระดับการขาดสารไอโอดีน ในพื้นที่ p Chavala Dhendhanoo, 1999