Iodine

1. Iodine By Alix, Kaitlin, Michele, Lindsay, and Allana 1

2. Functions Required for the synthesis of the thyroid hormones Thyroxine (T4) and Triiodothyronine (T3) • Makes up 65% and 59% of their respective weights  • These hormones regulate many biochemical reactions including • Protein synthesis • Enzymatic activity These processes affect the heart, kidneys, pituitary gland, muscles and brain • Plays a role in growth and development • Control and regulate basal metabolic rates *May have beneficial roles in mammary dysplasia an fibrocytic breast disease. 2

3. Food Sources • Iodine is an essential trace mineral that is not naturally made by the body, and can only be acquired through dietary sources. • Iodine is added to all table salt in Canada • Processed foods may have higher levels of iodine because the addition of salts and preservatives • Best natural occurring source is salt water seafood • Iodine content varies depending on mineral content of the soil. 3

4. Absorption and Metabolism • Bioavailability of iodine is greater than 90%. Most iodine that is ingested is reduced to iodide and is absorbed almost completely, primarily in the small intestine. • Although, some iodine containing compounds (thyroid hormones) are absorbed intact. • Once in circulation, iodide is mainly removed by thyroid gland and kidneys. 4

5. Transport • The protein responsible for iodide transport is the sodium/iodide symporter • This symporter is located in the thyroid basal membrane and is used to transfer iodide from the circulation into the thyroid gland at a concentration gradient of 20-50 times the rate of plasma. • This ensures that the thyroid gland obtains sufficient amounts of iodide for hormone synthesis. 5

6. Storage and Excretion • The thyroid selectively concentrates iodide in amounts required for adequate thyroid hormone synthesis. • Several other tissues can also concentrate iodine, including salivary glands, gastric mucosa, breast and choroid plexus. • Most excretion of iodine occurs through the urine with the remainder excreted in the feces. 6

7. Iodine Deficiency Disorders (IDD) • Because iodine has a direct relation with the thyroid gland, chronic deficiency results in goiter; swelling of the thyroid gland and neck. Other symptoms may include: • Mental deficiency • Hair Loss • Fatigue • Hearing and speech defects • Stunted growth • Other neurological disorders • Increased occurrences of fibrocystic breast disorder and breast cancer • Replacement therapy with thyroid hormones alone will increase total body iodine deficiency, making matters worse. 7

8. The Gold Standard Method Urinary iodine estimation is the gold standard employed for the assessment of iodine status and of IDD There are 4 methods of assessing IDD, however, the urinary Iodine excretion test is the most widely used biochemical method. The Three Methods are: • Goiter Growth Rate by measuring the size of the thyroid gland • Blood concentration of Thyroid Stimulating Hormone (THS), • Blood concentrations of Thyroglobulin 8

9. Thyroid Size • By neck palpation: Preformed by feeling the area of the neck where the thyroid gland is located to gain a relative measurement that is then compared to a size chart to determine the stage of deficiency. • By ultrasound: Preformed by using an ultrasonic device to determine the size of the goiter as well. However, this method provides a better measurement of the gland in mild cases when it may be small and is not as visible on the body. 9

10. Problems with…Goiter Growth Rate Method • When Iodine levels are low, the pituitary gland secretes more thyroid stimulating hormone to promote iodine uptake by the thyroid . This is done to produce more thyroid hormones that are lacking in the blood. Increased uptake of iodine causes the thyroid gland in the neck to enlarge. • Measuring the size of the thyroid gland provides a better reflection of the past, rather than present iodine status and the gland my not return to normal for several months to years after the deficiency has been addressed. • This method is also not recommended for children, as they have relatively small thyroid glands, which makes the measurements difficult to attain. 10

11. TSH Measurement • A measurement of the thyroid stimulating hormone is taken from either serum or whole blood. This is mainly performed on new borns and is done via heel prick approximately 72 hours after birth to allow for the levels to stabilize after the stress of the birthing process. 11

12. Problems with…TSH Measurement • When iodine levels are low, the thyroid gland cannot synthesize sufficient thyroid hormones. When blood concentration of these hormones gets too low, thyroid stimulating hormone (TSH) is secreted by the pituitary gland to stimulate hormone synthesis. • TSH measurements of the blood can be used to identify severe cases of IDD in adults, however in borderline deficiencies, TSH levels may be within range, while iodine concentrations excreted in the urine are low. • TSH measurement is not a sensitive indicator for adults, however it can be used in new born infants to assess the adequacy of thyroid hormone in the brain. This can be used as an indicator of hypothyroidism and is important to detect due to the impact it has on central nervous system development in children. 12

13. Thyroglobulin Concentration • Thyroglobulin is measured in serum and from this value an average iodine intake can be established. The levels of thyroglobulin and iodine intake are inversely related in that when thyroglobulin levels are high, there is a possibility of iodine deficiency. 13

14. Problems with…Thyroglobulin Concentration • Thyroglobulin is the most abundant thyroid protein and its levels reflect iodine concentration over a period of months. When iodine levels are low, the turnover rate of thyroid gland cells is increased, which releases more thyroglobulin into the blood in an effort to increase thyroid hormone production. This may be especially useful to observe short term changes in thyroid. • Due to lack of standardization processes, no cutoff point has been established and it is worth noting that thyroglobulin levels at birth are higher than in older children and adults, therefore possibly resulting in unreliable data. 14

15. Other Tests: • Thyroxine & Triiodo-thyronine Concentration: Levels of these hormones are measured in serum and can be used as a measure of thyroid function. However, these results can be normal even in a case of severe deficiency and low levels can simply be a result of fasting. • Radioactive Iodine Uptake: A dose of radioactive iodine is administered that will be concentrated in the thyroid gland, this will be used to determine thyroid function. These results are also subject to error as the uptake can be altered by hyperthyroidism, hypothyroidism, variations in renal function and some medications. 15

16. The Gold Standard (Why is it best?) • Urinary iodine level does not reflect thyroid function, which may alter the results from the previous 3 tests. The concentration of iodine in the urine is a direct result of dietary iodine. Over 90% of iodine intake is excreted in the urine and using a 24 hour urine volume sample, average daily iodine intake can be calculated. • Fasting urine samples or 24 hour samples may be taken and several different methods of analysis can be used to determine the iodine concentration. • Studies have shown this to be the most valid test and it is an indicator of immediate iodine inadequacy in the diet, rather than observing the damages resulting from a long term deficiency. This is beneficial for the prevention of damage from deficiency. This method can also be used to assess excess levels of iodine in the diet. • Can be done in the field • Suitable for children and adults • Relatively simple and inexpensive • Approved by WHO/UNICEF/ICCIDD 16

17. Evidence used to set the EAR • The estimated average requirement was set to provide a sufficient intake of iodine intake to allow for adequate production of thyroid hormones in order to prevent IDD • Evidence used to set the EAR: thyroidal radioiodine accumulation and turnover studies  Indicators for estimating the requirements:   • The affinity of the thyroid gland for iodine is estimated by the fraction of an orally administered dose of active radioiodine  that is concentrated in the thyroid gland • The thyroid concentrates more radioactive iodine in deficiency and less in when it is in excess 17

18. Iodine EAR and RDA Summary EAR for Men (adults ages 19 years or older) • 95 ug/day of iodine EAR for Women (adults 19 years or older) • 95 ug/day iodine • There is no evidence to suggest that that iodine requirements are altered with aging • the CV was calculated to be 40%, large variation due to complexity of experimental design and calculations to estimate turnover • RDA = EAR + 2(CV) in order to cover 98% the needs of individuals in the population RDA for Men (adults 19 years and older) • 150 ug/day of iodine RDA for Women (adults 19 years and older) • 150 ug/day of iodine 18

19. Radioiodine Accumulation and Turnover Studies Fischer and Oddie, 1969: • 18 men and women (aged 21 - 48 years) • average accumulation of radioiodine was 91.2 ug/day • accumulation of radioiodine by the thyroid gland correlated well with urinary radioiodine excretion DeGroot, 1966: • measured iodine turnover in 4 normal subjects • Three methods used: 1. Absolute Iodine Uptake (method of Riggs, 1952) --> 21 - 97 ug/day 2. Thyroid Hormone Secretion (method of Berson and Yalow, 1954) --> 69 -171 ug/day 3.  Thyroid Hormone Secretion (method of Ermans et al., 1963) --> 49 - 147 ug/day Supporting Data: • a study by Vought and London 1976: balance study of 13 subjects • the obligatory amount of iodine excreted was 57 ug/day when administered 100 ug/day with a slight positive balance observed • balance study has limitations, only supporting evidence 19

20. Strengths/Weaknesses of Evidence Strengths: • thyroid accumulation and turnover are well validated studies • used multiple studies and supporting evidence to set the EAR • accumulation of radioiodine correlates well with urinary iodine excretion Weaknesses: • all studies used to set the EAR are at least 50 years old • study sample are small and therefore representativeness is questionable • states there is no evidence to suggest a change in requirement due to age, has research been done to confirm this? What about the elderly? Factors that effect radioiodine uptake: • thyroidal over production of hormone • hypothyroidism • sub acute thyroiditis • many chemical and medicinal products * in order for turnover studies to be valid subjects are assumed adequate iodine status and are euthyroid 20

21. Upper limit and Toxicity of Iodine Upper limit: • >19 = 1,100mcg (including pregnant and lactating women). • 1-19 = 50mcg • Infants = 150mcg Toxicity symptoms • Similar to iodine deficiency • Goiter (thyroid enlargement) • Hyperthyroidism*  • Thyroid papillary cancer* • Increase incidence of autoimmune thyroid disease* *Generally only found in subpopulations where iodine intake is normally low. Especially occurs in elderly women who have has low intakes of iodine throughout their life and people with preexisting abnormalities of the thyroid gland. 

22. Further research The only accurate biomarker that we currently use is the urine test. Further research would be required to better assess iodine status. • Goiter Growth Rate - Doesn’t represent current iodine status, only long term status. • Blood concentration of Thyroid Stimulating Hormone (THS) – only used to detect severe deficiency, not very useful for inadequate iodine intake. • Blood concentrations of Thyroglobulin – only reflects long term deficiency, no standardized process or cut off points for blood concentrations of thyroglobulin. • A better understanding of the role of T4 on brain development • Role of Iodine in other diseases • Correlation data on the effect of Iodine intake on cancers

23. Key Points: Iodine • Is required for the synthesis of the thyroid hormones Thyroxine (T4) and Triiodothyronine (T3). • Chronic iodine deficiency and toxicity results in goiter - the swelling of the thyroid gland due to over active thyroid stimulation. • The gold standard method to assess iodine status is a urine sample. • The EAR was set to provide a level of iodine intake that would allow for sufficient production of the thyroid hormone to prevent Iodine Deficiency Disorders.

24. Key Points: Iodine • EAR = 95mcg/day for men and women > 19 • RDA = 150mcg/day for men and women >19 • UL = 1,100mcg/day for men and women >19

25. References • Otten, J., Hellwig, J., Meyers, L. (2006). Dietary Reference Intakes: The Essential Guide to Nutrient Requirements.  Retrieved from The National Academies Press: http://www.nap.edu/openbook.php?record_id=11537&page=320 • Dieticians of Canada (2010). Food Sources of Iodine. Retrieved from http://www.dietitians.ca/Nutrition-Resources-A-Z/Fact-Sheet-Pages(HTML)/Minerals/Food-Sources-of-Iodine.aspx • Gibson, R. (2005). Principles of Nutritional Assessment. New York: Oxford University Press. • Josh, i. A. (2006). Assessment of IDD problem by estimation of urinary iodine among school children. Retrieved from PubMed: http://www.ncbi.nlm.nih.gov/pubmed/17017401 • Zimmermann, M. (2008). Methods to assess iron and iodine status. Retrieved from PubMed: http://www.ncbi.nlm.nih.gov/pubmed/18598585 25