Useful links and references

Useful links and further reading on iodine biomarkers

Iodine Global Network

The Iodine Global Network (formerly the International Council for the Control of Iodine Deficiency Disorders, ICCIDD), is a non-profit non-governmental organisation that was established in 1986. It has the strategic goal to attain optimal iodine nutrition worldwide. The IGN core role is to advise on scientific and policy issues to achieve optimal iodine nutrition, in partnership with over 100 regional and national coordinators and partner agencies including UNICEF, the Global Alliance for Improved Nutrition and Nutrition International. The IGN provides numerous resources for program managers and researchers working on iodine nutrition.
– IGN have created a resource of information for programme managers on iodine, and offer a regularly-updated global scorecard of worldwide iodine status.

World Health Organization

The World Health Organisation (WHO) provides guidance on the assessment of population iodine status: Assessment of Iodine Deficiency Disorders and Monitoring their Elimination. A Programme Manager’s Guide; available here.

The WHO Vitamin and Mineral Nutrition Information Service (VMNIS) have several resources on iodine:

Biomarkers of Nutrition for Development

For a comprehensive review of iodine biology and biomarkers, including the interpretation of biomarker results and constraints around using them, consult the Biomarkers of Nutrition for Development (BOND) review for iodine, available as an open-access resource here.

UNICEF

UNICEF Nutrition features a wealth of information on iodine, including:

US Centers for Disease Control and Prevention (CDC)

Along with running the EQUIP scheme to ensure the quality of urinary iodine assessment (see page 4), CDC have several resources on iodine:

Iodine and breastfeeding
International Micronutrient Malnutrition Prevention and Control (IMMPaCt) Program, which works with global partners to contribute CDC skills and resources to eliminate micronutrient malnutrition among vulnerable populations throughout the world. IMMPaCt focuses primarily on helping eliminate deficiencies in iron, vitamin A, iodine, folate, and zinc.

EUthyroid

The EUthyroid Project is a pan-European initiative with the aim of investigating and optimising the iodine intake of the European population, in cooperation with national European authorities. One of its primary goals is to optimise and harmonise population iodine biomarker assessment methods across Europe. Euthyroid has created guidelines for researchers conducting population studies, with a focus on the monitoring of iodine deficiency disorders. It includes general recommendations and issues related to study planning; detailed instructions and recommendations for specimen collection and sample handling, and an overview of laboratory analysis related to urinary iodine concentration and thyroid function parameters. The guideline is available here.

The American Thyroid Association

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. The ATA produces numerous guidelines and manuals on thyroid health.

The European Thyroid Association

The aims of the European Thyroid Association are to promote knowledge in the thyroid field (fundamental and clinical) and improve knowledge of the thyroid gland and its diseases. Similarly to the ATA, the ETA produce many useful guidelines and publications.

Stinca S, Andersson M, Weibel S, Gowachirapant S, Aeberli-Herter I, Hess SY, Jaiswal N, Jukić T, Kusic Z, Mabapa NS, Nepal AN, San Luis TOL, Jia QZ, Zimmermann MB. Dried blood spot thyroglobulin as a biomarker of iodine status in pregnant women. J Clin Endocrinol Metab. 2017 Jan 1;102(1):23-32. doi: 10.1210/jc.2016-2829

BREAST MILK IODINE CONCENTRATION AS BIOMARKER FOR IODINE STATUS IN LACTATING WOMEN:

Dold S, Baumgartner J, Zeder C, Krzystek A, Osei J, Haldimann M, Zimmermann MB, Andersson M. Optimization of a new mass spectrometry method for measurement of breast milk iodine concentrations and an assessment of the effect of analytic method and timing of within-feed sample collection on breast milk iodine concentrations. Thyroid. 2016 Feb;26(2):287-95. doi: 10.1089/thy.2015.0317.

Dold S, Zimmermann MB, Aboussad A, Cherkaoui M, Jia QZ, Jukic T, Kusic Z, Quirino A, Sang Z, Luis TOL, Vandea E, Andersson M. Breast milk iodine concentration is a more accurate biomarker of iodine status than urinary iodine concentration in exclusively breastfeeding women. J Nutr. 2017;147:528-537. doi: 10.3945/jn.116.242560.

Page 1: Iodine: home // Page 2: Importance of iodine for health // Page 3: Human biomarkers for measuring iodine intake and status: summary // Page 4: Urinary Iodine Concentration // Page 5: Thyroglobulin // Page 6: Other methods // Page 7: Quality control and technical assistance // Page 8: Useful links // Page 9: References

1. Delange F, Ermans A 1996 Iodine deficiency. In: Braverman LE, Utiger RD, (eds) Werner and Ingbar’s The thyroid: a fundamental and clinical text. Vol.

2. Zimmermann MB, Boelaert K 2015 Iodine deficiency and thyroid disorders. The lancet Diabetes & endocrinology 3:286-295.

3. Eastman CJ, Zimmermann MB 2000 The Iodine Deficiency Disorders. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP, (eds) Endotext. Vol. MDText.com, Inc., South Dartmouth (MA).

4. Farebrother J, Zimmermann M, Assey V, Castro MC, Cherkaoui M, Fingerhut R, Jia Q, Jukic T, Makokha A, San Luis TOL, Jr., Wegmuller R, Andersson M 2019 Thyroglobulin is markedly elevated in 6-24-month-old infants at both low and high iodine intakes and suggests a narrow optimal iodine intake range. Thyroid.

5. Shi X, Han C, Li C, Mao J, Wang W, Xie X, Li C, Xu B, Meng T, Du J, Zhang S, Gao Z, Zhang X, Fan C, Shan Z, Teng W 2015 Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: A cross-sectional study of 7190 pregnant women in China. Journal of Clinical Endocrinology and Metabolism 100:1630-1638.

6. Stinca S, Andersson M, Weibel S, Herter-Aeberli I, Fingerhut R, Gowachirapant S, Hess SY, Jaiswal N, Jukic T, Kusic Z, Mabapa NS, Nepal AK, San Luis TO, Zhen JQ, Zimmermann MB 2017 Dried Blood Spot Thyroglobulin as a Biomarker of Iodine Status in Pregnant Women. J Clin Endocrinol Metab 102:23-32.

7. Zimmermann MB, Aeberli I, Andersson M, Assey V, Yorg JA, Jooste P, Jukic T, Kartono D, Kusic Z, Pretell E, San Luis TO, Jr., Untoro J, Timmer A 2013 Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 mug/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab 98:1271-1280.

8. Bougma K, Aboud FE, Harding KB, Marquis GS 2013 Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis. Nutrients 5:1384-1416.

9. Rohner F, Zimmermann M, Jooste P, Pandav C, Caldwell K, Raghavan R, Raiten DJ 2014 Biomarkers of nutrition for development-iodine review. The Journal of nutrition 144:1322S-1342S.

10. Yarrington C, Pearce EN 2011 Iodine and pregnancy. J Thyroid Res 2011:934104.

11. Zimmermann MB 2011 The role of iodine in human growth and development. Semin Cell Dev Biol 22:645-652.

12. Pearce EN, Lazarus JH, Moreno-Reyes R, Zimmermann MB 2016 Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr 104 Suppl 3:918S-923S.

13. Institute of Medicine, Academy of Sciences, USA 2001 Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. National Academy Press, Washington DC.

14. Dold S, Zimmermann MB, Jukic T, Kusic Z, Jia Q, Sang Z, Quirino A, San Luis TOL, Fingerhut R, Kupka R, Timmer A, Garrett GS, Andersson M 2018 Universal Salt Iodization Provides Sufficient Dietary Iodine to Achieve Adequate Iodine Nutrition during the First 1000 Days: A Cross-Sectional Multicenter Study. The Journal of nutrition 148:587-598.

15. Dold S, Zimmermann MB, Aboussad A, Cherkaoui M, Jia Q, Jukic T, Kusic Z, Quirino A, Sang Z, San Luis TO, Vandea E, Andersson M 2017 Breast Milk Iodine Concentration Is a More Accurate Biomarker of Iodine Status Than Urinary Iodine Concentration in Exclusively Breastfeeding Women. The Journal of nutrition 147:528-537.

16. World Health Organization 2007 Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. – 3rd ed. In: Press W, (ed), Geneva.

17. United Nations Children’s Fund 2018 Guidance on the monitoring of salt iodization programmes and determination of population iodine status.

18. Stinca S, Andersson M, Erhardt J, Zimmermann MB 2015 Development and Validation of a New Low-Cost Enzyme-Linked Immunoassay for Serum and Dried Blood Spot Thyroglobulin. Thyroid25:1297-1305.

19. Zimmermann MB, de Benoist B, Corigliano S, Jooste PL, Molinari L, Moosa K, Pretell EA, Al-Dallal ZS, Wei Y, Zu-Pei C, Torresani T 2006 Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. J Clin Endocrinol Metab 91:4881-4887.

20. Demers LM, Spencer CA 2003 National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines. Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. .

21. Zimmermann MB, Moretti D, Chaouki N, Torresani T 2003 Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt. Am J Clin Nutr 77:1453-1458.

22. Farebrother J, Zimmermann M, Andersson A 2019 Excessive iodine intake: sources, assessment, extent and effects on thyroid function (Accepted). Ann N Y Acad Sci.

23. Zimmermann MB, Andersson M 2012 Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev 70:553-570.

24. König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB 2011 Ten repeat collections for urinary iodine from spot samples or 24-h samples are needed to reliably estimate individual iodine status in women. The Journal of nutrition 141:2049-2054.

25. Karmisholt J, Laurberg P, Andersen S 2014 Recommended number of participants in iodine nutrition studies is similar before and after an iodine fortification programme. European journal of nutrition 53:487-492.

26. Vejbjerg P, Knudsen N, Perrild H, Laurberg P, Andersen S, Rasmussen LB, Ovesen L, Jorgensen T 2009 Estimation of iodine intake from various urinary iodine measurements in population studies. Thyroid 19:1281-1286.

27. Haap M, Roth HJ, Huber T, Dittmann H, Wahl R 2017 Urinary iodine: comparison of a simple method for its determination in microplates with measurement by inductively-coupled plasma mass spectrometry. Sci Rep 7:39835.

28. Ristic-Medic D, Piskackova Z, Hooper L, Ruprich J, Casgrain A, Ashton K, Pavlovic M, Glibetic M 2009 Methods of assessment of iodine status in humans: a systematic review. Am J Clin Nutr 89:2052S-2069S.

29. Andersen S, Karmisholt J, Pedersen KM, Laurberg P 2008 Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br J Nutr 99:813-818.

30. Remer T, Montenegro-Bethancourt G, Shi L 2014 Long-term urine biobanking: storage stability of clinical chemical parameters under moderate freezing conditions without use of preservatives. Clin Biochem 47:307-311.

31. Sellitti DF, Suzuki K 2014 Intrinsic regulation of thyroid function by thyroglobulin. Thyroid 24:625-638.

32. Suzuki K, Kohn LD 2006 Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin. The Journal of endocrinology 189:247-255.

33. Luo Y, Ishido Y, Hiroi N, Ishii N, Suzuki K 2014 The Emerging Roles of Thyroglobulin. Advances in Endocrinology 2014:1-7.

34. Marino M, Pinchera A, McCluskey RT, Chiovato L 2001 Megalin in thyroid physiology and pathology. Thyroid 11:47-56.

35. Spencer CA, Wang CC 1995 Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls. Endocrinology and metabolism clinics of North America 24:841-863.

36. Targovnik HM 2013 Thyroglobulin: structure, function, and biosynthesis. In: Braverman LE, Cooper DS, (eds) Werner and Ingbar’s The Thyroid: A Fundamental and Clinical Text. Vol. Lippincott Williams & Wilkins, Philadelphia, PA, 74-92.

37. Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, Thomas S, Thomas T, Winichagoon P, Srinivasan K, Zimmermann MB 2017 Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. The lancet Diabetes & endocrinology5:853-863.

38. Andersen S, Noahsen P, Westergaard L, Laurberg P 2017 Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status. Br J Nutr 117:441-449.

39. Netzel BC, Grebe SK, Carranza Leon BG, Castro MR, Clark PM, Hoofnagle AN, Spencer CA, Turcu AF, Algeciras-Schimnich A 2015 Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes. J Clin Endocrinol Metab 100:E1074-1083.

40. Stinca S 2016 Serum and dried blood spot thyroglobulin as a novel biomarker of iodine status in pregnancy. Zurich, Switzerland: Human Nutrition Laboratory, Institute for Food, Nutrition and Health, ETH Zurich.

41. Spencer C, Fatemi S 2013 Thyroglobulin antibody (TgAb) methods – Strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab 27:701-712.

42. Latrofa F, Ricci D, Bottai S, Brozzi F, Chiovato L, Piaggi P, Marino M, Vitti P 2018 Effect of Thyroglobulin Autoantibodies on the Metabolic Clearance of Serum Thyroglobulin. Thyroid 28:288-294.

43. Okosieme OE, Lazarus JH 2004 Thyroglobulin: a thyroid autoantigen and marker of DTC. Thyroid Disease October.

44. Knudsen N, Bulow I, Jorgensen T, Perrild H, Ovesen L, Laurberg P 2001 Serum Tg–a sensitive marker of thyroid abnormalities and iodine deficiency in epidemiological studies. J Clin Endocrinol Metab 86:3599-3603.

45. Krejbjerg A, Bjergved L, Bulow Pedersen I, Carle A, Knudsen N, Perrild H, Ovesen L, Banke Rasmussen L, Laurberg P 2016 Serum thyroglobulin as a biomarker of iodine deficiency in adult populations. Clin Endocrinol (Oxf) 85:475-482.

46. Gao Y, Yuan Z, Yu Y, Lu H 2007 Mutual interference between serum thyroglobulin and antithyroglobulin antibody in an automated chemiluminescent immunoassay. Clin Biochem 40:735-738.

47. Francesco L, Debora R, Sara B, Federica B, Luca C, Paolo P, Michele M, Paolo V 2018 Effect of Thyroglobulin Autoantibodies on the Metabolic Clearance of Serum Thyroglobulin. Thyroid : official journal of the American Thyroid Association 28:288-294.

48. Segni M 2017 Disorders of the thyroid gland in infancy, childhood and adolescence. https://www.ncbi.nlm.nih.gov/books/NBK279032/ (accessed 19th July 2018). Endotext.

49. de Benoist B, Pretell EA, Pearce EN, Delange F, Fujieda K, Moosa K, Braverman LE, Molinari L, Jooste PL, Hess SY, Shishiba Y, Ito Y, Zimmermann MB 2004 New reference values for thyroid volume by ultrasound in iodine-sufficient schoolchildren: a World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group Report. The American Journal of Clinical Nutrition 79:231-237.

50. Li M, Eastman CJ 2010 Neonatal TSH screening: is it a sensitive and reliable tool for monitoring iodine status in populations? Best Pract Res Clin Endocrinol Metab 24:63-75.

51. Peters C, Brooke I, Heales S, Ifederu A, Langham S, Hindmarsh P, Cole TJ 2016 Defining the Newborn Blood Spot Screening Reference Interval for TSH: Impact of Ethnicity. J Clin Endocrinol Metab 101:3445-3449.

52. Franklyn JA, Boelaert K 2012 Thyrotoxicosis. Lancet (London, England) 379:1155-1166.

53. Dold S, Baumgartner J, Zeder C, Krzystek A, Osei J, Haldimann M, Zimmermann MB, Andersson M 2016 Optimization of a New Mass Spectrometry Method for Measurement of Breast Milk Iodine Concentrations and an Assessment of the Effect of Analytic Method and Timing of Within-Feed Sample Collection on Breast Milk Iodine Concentrations. Thyroid 26:287-295.

54. Huynh D, Zhou SJ, Gibson R, Palmer L, Muhlhausler B 2015 Validation of an optimized method for the determination of iodine in human breast milk by inductively coupled plasma mass spectrometry (ICPMS) after tetramethylammonium hydroxide extraction. J Trace Elem Med Biol 29:75-82.

Useful links and references

Useful links and further reading on iodine biomarkers

Iodine Global Network

World Health Organization

The WHO Vitamin and Mineral Nutrition Information Service (VMNIS) have several resources on iodine:

Biomarkers of Nutrition for Development

UNICEF

US Centers for Disease Control and Prevention (CDC)

EUthyroid

The American Thyroid Association

The European Thyroid Association

Further reading

DRIED BLOOD SPOT THYROGLOBULIN AS A BIOMARKER FOR IODINE STATUS:

BREAST MILK IODINE CONCENTRATION AS BIOMARKER FOR IODINE STATUS IN LACTATING WOMEN:

Continue reading about Iodine:

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