Iodine

Iodine is necessary for proper foetal brain development, and there is mixed evidence that high levels of iodine may affect thyroid function 1. The most usual indicator of population iodine status is the median urinary iodine concentration (UIC) of the population.

There are clinical and other biological indicators of iodine status, including goitre and thyroid volume by ultrasonography, however these are not currently recommended for large national cross-sectional surveys. Assessment of goitre is not recommended either, because it is a more subjective method, especially if conducted by palpation. More importantly, thyroid size responds very slowly after the introduction of an intervention (such as iodized salt) to improve iodine intake, and does not provide a reliable indication of recent individual or population iodine intake 1.

More recently, thyroglobulin has been proposed as a sensitive indicator of both low and excess iodine intake for use at the population level, following a U‐shaped association with the urinary iodine concentration (UIC) in school-age children, pregnant women and infants. Due to high day‐to‐day variability, however, the utility of thyroglobulin as an individual biomarker of iodine status is uncertain 2.

Urinary iodine concentration (UIC):

The recent iodine intake of an individual can be assessed by measuring urinary iodine excretion (UIE), the iodine level in a 24-hour collection of urine that mitigates diurnal variations in iodine excretion. However, it is not feasible to include 24-hour urine collections as part of a large cross-sectional survey, and thus it is not possible to estimate the iodine status of individual survey participants. With a sufficiently large number of single urine samples, the median UIC will represent the status of the entire sample population.

Specimen collection and management: Urine samples are normally collected at the household but depending on the survey they can be collected from a clinic or laboratory. Samples do not require refrigeration but are usually kept in cool boxes or refrigerated with other specimens until they are processed.

Urine samples are relatively easy to collect from older children and adults. Only a small amount of urine is required (approximately 1 mL) for duplicate laboratory testing of iodine content. Infants and very young children may have difficulty urinating on demand or into the collection cup.

Biomarker analysis: The urinary iodine ammonium persulfate method 3 is considered the “gold standard” assay for analysis of UIC. Reagents and calibration materials, including ammonium persulfate, arsenious acid, ceric ammonium sulphate solutions and sulfuric acid are necessary for the sample analysis. A sample of 250 µL is needed, but a minimum of 1 mL of urine should be collected for potential repeat analysis. It is recommended to use internal quality controls during each analytical run in order to assess the accuracy and precision of the results. CDC also offers the Ensuring the Quality of Urinary Iodine Procedures (EQUIP) programme for urinary iodine, available globally to all laboratories so that bias and imprecision of their method can be tested against the CDC method three times a year 4. The urinary iodine ammonium persulfate method is relatively simple to perform but requires special attention to prevent iodine contamination of the laboratory area and equipment. Although urinary iodine excretion can be expressed in relation to creatinine excretion (µg iodine/g creatinine), the ratio of urinary iodine to creatinine can be misleading 5. Therefore, WHO recommends reporting urinary iodine as µg/L 6.

Approximate budget requirements for analysis: Instrumentation needed for this method includes a spectrophotometer, laboratory glassware, regents, a vortex, a heating block with a timer, and various pipettes (costing approximately US$ 10 000). The cost for materials and supplies is approximately US$ 2 - 5 per sample.

Interpretation of results: Table 3.6 presents the median UIC that indicates iodine status among different population groups 6. It is important to note that only population-level assessments of iodine status are possible from the survey methodology of casual, spot urine sample collection. Iodine status estimates based on the methodology of casual spot urine sample collection cannot be used to classify individual status and should not be presented as a prevalence of deficiency or adequacy 1. The information provided in Table 3.6 is frequently misinterpreted to reflect the situation of individuals. The correct interpretation is that populations with a median urinary iodine <20 μg/L have “severe” iodine deficiency, populations with a median urinary iodine 20-49 μg/L have “moderate” iodine deficiency, and populations with a median urinary iodine 20-49 μg/L have “mild” iodine deficiency.

Table 3.6. Epidemiologic criteria for assessing population-level iodine nutrition based on median urinary iodine concentrations in different population groupsa

Median urinary iodine concentration (μg/L)
Indication of population iodine intake
Indication of population iodine status
School-age children (6-12 years of age)
<20
Insufficient
Severe iodine deficiency
20-49
Insufficient
Moderate iodine deficiency
50-99
Insufficient
Mild iodine deficiency
100-199b
Adequate
Adequate iodine nutrition
200-299
Above requirements
May pose a slight risk of more than adequate iodine intake in these populations
≥300
Excessivec
Risk of adverse health consequences (iodine-induced hyperthyroidism, autoimmune thyroid disease)
Pregnant women
<150
Insufficient
150-249
Adequate
250-499
Above requirements
≥500
Excessivec
Lactating women and children under 2 years of age
≥500
Insufficient
≥100
Adequate

a Source: reference 6

b A UIC range of 100-299 µg/L has been proposed to indicate optimal iodine status among school age children1,7.

c The term “excessive” means in excess of the amount required to prevent and control iodine deficiency.

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  1. Guidance on the monitoring of salt iodization programmes and determination of population iodine status. New York: United Nations Children’s Fund; 2018 (https://www.unicef.org/nutrition/files/Monitoring-of-Salt-Iodization.pdf, accessed 14 June 2020).  2 3

  2. Farebrother J, Zimmermann MB, Andersson M. Excess iodine intake: sources, assessment, and effects on thyroid function. Ann NY Acad Sci. 2019;1446:44–65. doi:10.1111/nyas.14041. 

  3. Pino S, Fang SL, Braverman LE. Ammonium persulfate: a safe alternative oxidizing reagent for measuring urinary iodine. Clin Chem. 1996;42:239–43. 

  4. Caldwell KL, Makhmudov AR, Jones RL, Hollowell JG. EQUIP: a worldwide program to ensure the quality of urinary iodine procedures. Accred Qual Assur. 2005;10:356–61. doi.org/10.1007/s00769-005-0003-x. 

  5. Hollowell JG, Staehling NW, Hannon WH, Flanders DW, Gunter EW, Maberly GF et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971–1974 and 1988–1994). J Clin Endocrinol Metab. 1998;83:3401–8. 

  6. Urinary iodine concentrations for determining iodine status in populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2013 (WHO/NMH/NHD/EPG/13.1; https://apps.who.int/iris/bitstream/handle/10665/85972/WHO_NMH_NHD_EPG_13.1_eng.pdf, accessed 15 July 2019).  2

  7. Zimmermann MB, Aeberli I, Andersson M, Assey V, Yorg JA, Jooste P et al. 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 μg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab. 2013;98:1271–80. doi: 10.1210/jc.2012-3952.