The size of the thyroid gland changes inversely in response to iodine intake, and due to a relatively long lag time, it can give an indication of historical iodine intakes, though it is not suitable to assess response to recent changed in iodine intakes. Goitre means a thyroid gland that is enlarged, with a volume greater than the terminal phalanx of the thumbs of the subject being examined (16). This non-invasive, empirical technique has been used in many epidemiological surveys of iodine nutrition and endemic goitre, and population total goitre rate was one of the first measurements undertaken to assess the iodine status of a population. A more precise assessment of thyroid volume (Tvol) by ultrasound has been widely used to assess iodine deficiency. Tvol tends to decrease with time following initiation of iodine supplementation in previously endemic countries, though because Tvol can also increase with excessive iodine intakes, Tvol is not a sensitive stand-alone biomarker to distinguish between deficient and excessive population iodine intakes.
The assessment of Tvol by palpation requires careful training by medical personnel. The basic method is given in the WHO Guide for Programme Managers (2007).
Measuring thyroid size by ultrasound is a safe and non-invasive technique that can be done in 2-3 minutes per subject in the field. It requires specialist training to be undertaken correctly because results may be biased by inter-observer variation (i.e. between different technicians). It is more accurate than palpation.
Reference values have been proposed by a WHO/Nutrition for Health and Development Iodine Deficiency Study Group Report (49), available here.
Method for determining thyroid size by ultrasonography (courtesy of IGN, linked to the WHO Guide for Programme Managers (2007).)
Method for determining thyroid size by ultrasonography (courtesy of EUthyroid)
Thyroid Stimulating Hormone (TSH)
TSH, also known as thyrotropin, is secreted from the pituitary gland in response to changes in circulating thyroid hormone, in an intricate negative feedback mechanism involving the hypothalamus-pituitary-thyroid (HPT) axis. Serum TSH rises when T4 levels are low, to stimulate the thyroid gland to produce more T4. When T4 levels are high, TSH falls. Moderate to severe iodine deficiency may lower circulating T4 levels, therefore moderately-to-severe iodine deficient populations may have a higher serum TSH level than iodine-sufficient populations (16).
TSH is routinely measured in many countries as part of neonatal congenital hypothyroidism screening programs, usually by heel prick. It is not recommended to monitor TSH as a biomarker of iodine surveillance, though secondary analysis of neonatal data can help establish population iodine status (16).The prevalence of neonates with elevated TSH levels is therefore a good indication of moderate-to-severe iodine deficiency during pregnancy, but its value in mild iodine deficiency is uncertain (50, 51).
In addition to newborn screening, TSH is routinely used in clinical practice as a sensitive marker for hypo- and hyperthyroidism, and can be used as a diagnostic tool (alone or in conjunction with other tests) for thyrotoxicosis (52). Paired with T4 data, population-level TSH values are valuable in estimating population prevalence of thyroid dysfunction.Age-specific reference values should always be used (48).
When a sensitive TSH assay is used on samples collected 3-4 days after birth a <3% frequency of TSH values >5 mIU/L indicates population iodine sufficiency (16).
Note: interpretation can be confounded by use of iodine-containing antiseptics at birth (16).
For more guidance, see the WHO Guide for Programme Managers (2007).
Breast milk iodine concentration
During lactation, breast milk iodine concentration is a more accurate biomarker of iodine status than urinary iodine concentration in exclusively breastfeeding women (15). It is recommended as an adjunct to urinary iodine concentration measurement in lactating women.
Analysis of breast milk iodine concentration (BMIC) can be performed using ICP-MS.
Examples of ICP-MS methods in published literature (53, 54) are found via the following open-access links:
Dold et al. Thyroid, 2016.
Huynh et al. J Trace Elem Med Biol 2015.