3.2.3 Iodine deficiency disorders

Iodine (atomic weight 126.9 g/mol) is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life (1). The native iodine content of most foods and beverages is low, and the most commonly consumed foods provide 3–80 μg/serving (1). The major dietary sources of iodine in the United States of America and Europe are bread and milk (2). Boiling, baking, and canning of foods containing iodized salt cause only small losses (≤10%) of iodine content. The iodine content in foods is also influenced by iodine-containing compounds used in irrigation, fertilizers, livestock feed, dairy industry disinfectants, and bakery dough conditioners. The recommendations for iodine intake by age and population group (3) are shown in Table 3.2.3.1.

Iodide is rapidly and nearly completely absorbed (>90%) in the stomach and duodenum (4). Iodate, widely used in salt iodization, is reduced in the gut and absorbed as iodide. Thyroid clearance of circulating iodine varies with iodine intake; in conditions of adequate iodine supply, no more than 10% of absorbed iodine is taken up by the thyroid. In chronic iodine deficiency, this fraction can exceed 80% (1). Under normal circumstances, plasma iodine has a half-life of about 10 h, but this is reduced in iodine deficiency. During lactation, the mammary gland concentrates iodine and secretes it into breast milk to provide for the newborn. The body of a healthy adult contains 15–20 mg iodine, of which 70–80% is in the thyroid. In chronic iodine deficiency, the iodine content of the thyroid may fall to less than 20 μg. In iodine-sufficient areas, the adult thyroid traps about 60 μg iodine/day to balance losses and maintain thyroid hormone synthesis; the sodium-iodide symporter (NIS), transfers iodide into the thyroid at a concentration gradient 20–50 times that of plasma (5). Iodine comprises 65 and 59% of the weights of thyroxine (T₄) and triiodothyronine (T₃), respectively. Turnover is relatively slow; the half-life of T₄ is approximately 5 days and for T₃ it is 1.5–3 days. The released iodine enters the plasma iodine pool and can be taken up again by the thyroid or excreted by the kidney. More than 90% of ingested iodine is ultimately excreted in the urine.

In 1811, Courtois noted a violet vapour rising from burning seaweed ash, and Gay-Lussac subsequently identified the vapour as iodine, a new element. The Swiss physician Coindet, in 1813, hypothesized the traditional treatment of goitre with seaweed was effective because of its iodine content, and successfully treated goitrous patients with iodine (6). Two decades later, the French chemist Boussingault, working in the Andes Mountains, was the first to advocate prophylaxis with iodine-rich salt to prevent goitre. The French chemist Chatin was the first to publish, in 1851, the hypothesis that iodine deficiency was the cause of goitre. In 1883, Semon suggested myxoedema was due to thyroid insufficiency, and the link between goitre, myxoedema, and iodine was established when, in 1896, Baumann and Roos discovered iodine in the thyroid. In the first two decades of the 20th century, pioneering studies by Swiss and American physicians demonstrated the efficacy of iodine prophylaxis in the prevention of goitre and cretinism (6).

Only a few countries—Switzerland, some of the Scandinavian countries, Australia, the United States of America, and Canada—were completely iodine sufficient before 1990. Since then, globally, the number of households using iodized salt has risen from less than 20% to over 70%, dramatically reducing iodine deficiency. This effort has been spurred on by a coalition of international organizations, including the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), WHO, Micronutrient Initiative (MI), and Unicef, working closely with national iodine deficiency disorders (IDD) control committees and the salt industry; this informal partnership was established after the World Summit for Children in 1990.

In 2007, the WHO estimated nearly two billion individuals had an insufficient iodine intake, including one-third of all school-age children (7) (Table 3.2.3.2)). The lowest prevalence of iodine deficiency is in the Americas (10.6%), where the proportion of households consuming iodized salt is the highest in the world (c.90%). The highest prevalence of iodine deficiency is in Europe (52.0%), where the household coverage with iodized salt is the lowest (c.25%), and many of these countries have weak or nonexistent IDD control programmes. The number of countries where iodine deficiency remains a public health problem is 47. However, there has been progress since 2003; 12 countries have progressed to optimal iodine status and the percentage of school-age children at risk of iodine deficiency has decreased by 5%. However, iodine intake is more than adequate, or even excessive, in 34 countries, an increase from 27 in 2003. In Australia and the USA, two countries previously iodine sufficient, iodine intakes are falling. Much of Australia is now mildly iodine deficient, and in the USA the median urinary iodine is 160 μg/l, still adequate but one-half the median value of 321 μg/l found in the 1970s (8). These changes emphasize the importance of regular monitoring of iodine status in countries to detect both low and excessive intakes of iodine.

There are several limitations to these WHO prevalence data. First, extrapolation from a population indicator (median urinary iodine) to define the number of individuals affected is problematic, e.g. a country in which the children have a median urinary iodine of 100 μg/l would be classified as being iodine sufficient, yet at the same time 50% of children would be classified as having inadequate iodine intakes. Second, nationally representative surveys represent only 60% of the global population included in the WHO data, and subnational data may under- or overestimate the extent of iodine deficiency (7). Finally, there are insufficient data from nearly all countries to estimate the prevalence of iodine deficiency in pregnant women.

Iodine deficiency has multiple adverse effects on growth and development in animals and humans. These are collectively termed the IDD (Table 3.2.3.3) and they result from inadequate thyroid hormone production due to lack of sufficient iodine (1).

Thyroid enlargement (goitre) is the classic sign of iodine deficiency and can occur at any age, even in the newborn. It is a physiological adaptation to chronic iodine deficiency. As iodine intake falls, secretion of thyroid-stimulating hormone (TSH) increases in an effort to maximize uptake of available iodine, and TSH stimulates thyroid hypertrophy and hyperplasia. Initially, goitres are characterized by diffuse homogeneous enlargement, but, over time, nodules often develop (Fig. 3.2.3.1). Many thyroid nodules derive from a somatic mutation and are of monoclonal origin; the mutations appear to be more likely to result in nodules under the influence of a growth promoter, such as iodine deficiency. Iodine deficiency is associated with a high occurrence of multinodular toxic goitre, mainly seen in women older than 50 years. Large goitres may be cosmetically unattractive, can obstruct the trachea and oesophagus, and may damage the recurrent laryngeal nerves and cause hoarseness. Surgery to reduce goitre has significant risks, including bleeding and nerve damage, and hypothyroidism may develop after removal of thyroid tissue.

The most serious adverse effect of iodine deficiency in pregnancy is damage to the fetus. Maternal thyroxine crosses the placenta before the onset of fetal thyroid function at 10–12 weeks and represents up to 20–40% of T₄ measured in cord blood at birth. Normal levels of thyroid hormones are required for neuronal migration and myelination of the fetal brain, and lack of iodine irreversibly impairs brain development (9). Severe iodine deficiency during pregnancy increases the risk for stillbirths, abortions, and congenital abnormalities (1). Iodine treatment of pregnant women in areas of severe deficiency reduces fetal and perinatal mortality and improves motor and cognitive performance of the offspring (10). Severe iodine deficiency in utero causes a condition characterized by gross mental impairment along with varying degrees of short stature, deaf-mutism, and spasticity that is termed cretinism (1). Two distinct types—neurological and myxoedematous—have been described, but it may also present as a mixed form (Figs. 3.2.3.2a, b). The more common neurological cretinism has specific neurological deficits that include spastic quadriplegia with sparing of the distal extremities. The myxoedematous form is seen most frequently in central Africa, and has the predominant finding of profound hypothyroidism with thyroid atrophy and fibrosis. In areas of severe iodine deficiency, cretinism can affect 5–15% of the population. Iodine prophylaxis has completely eliminated the appearance of new cases of cretinism in previously iodine-deficient Switzerland and many other countries, but it continues to occur in isolated areas of western China.

The potential adverse effects of mild-to-moderate iodine deficiency during pregnancy are unclear. Maternal subclinical hypothyroidism (an increased TSH in the second trimester) and maternal hypothyroxinaemia (a free T₄ concentration <10th percentile at 12 weeks gestation) are associated with impaired mental and psychomotor development of the offspring (12). However, in these studies, the maternal thyroid abnormalities were unlikely to have been due to iodine deficiency. In Europe, several randomized controlled trials of iodine supplementation in mild-to-moderately iodine-deficient pregnant women have been done (13). Iodine reduced maternal and newborn thyroid size, and, in some, decreased maternal TSH. However, none of the trials showed an effect on maternal and newborn total or free thyroid hormone concentrations, the most important outcome, and none measured long-term clinical outcomes, such as maternal goitre, thyroid autoimmunity, or child development (13).

Although iodine deficiency in utero impairs fetal growth and brain development, its postnatal effects on growth and cognition are less clear. Cross-sectional studies of moderate to severely iodine deficient children have generally reported impaired intellectual function and fine motor skills; meta-analyses suggest populations with chronic iodine deficiency experience a reduction in IQ of 12.5–13.5 points (14). However, observational studies are often confounded by other factors that affect child development, and these studies could not distinguish between the persistent effects of in utero iodine deficiency and the effects of current iodine status. In a controlled trial in 10- to 12-year-old moderately iodine deficient children who received oral iodized oil or placebo, iodine treatment significantly improved information processing, fine motor skills, and visual problem solving compared to placebo (15). Thus, in children born and raised in areas of iodine deficiency, cognitive impairment is at least partially reversible by iodine repletion (15).

Data from cross-sectional studies on iodine intake and child growth are mixed, with most studies finding modest positive correlations. In five Asian countries, household access to iodized salt was correlated with increased weight-for-age and mid-upper arm circumference in infancy (16). In iodine-deficient children, impaired thyroid function and goitre are inversely correlated with insulin-like growth factor (IGF)-1 and IGF binding protein 3 (IGFBP3) concentrations. Iodine repletion in school-age children increased IGF-1 and IGFBP3 and improved somatic growth (16).

Overall, iodine deficiency produces subtle but widespread adverse effects in a population, including decreased educability, apathy, and reduced work productivity, resulting in impaired social and economic development. Because mild-to-moderate iodine deficiency affects up to 30% of the global population (7) and can impair cognition, iodine deficiency is likely to be a common cause of preventable mental impairment worldwide. The International Child Development Steering Group identified iodine deficiency as one of four key global risk factors for impaired child development where the need for intervention is urgent (17).

Four methods are generally recommended for assessment of iodine nutrition: (1) urinary iodine concentration, (2) the goitre rate, (3) serum TSH, and (4) serum thyroglobulin (3, 18). These indicators are complementary, in that urinary iodine is a sensitive indicator of recent iodine intake (days), thyroglobulin shows an intermediate response (weeks to months), while changes in the goitre rate reflect long-term iodine nutrition (months to years).

Two methods are available for measuring goitre: (1) neck inspection and palpation and (2) thyroid ultrasonography. By palpation, a thyroid is considered goitrous when each lateral lobe has a volume greater than the terminal phalanx of the thumbs of the individual being examined (3). However, palpation of goitre in mild iodine deficiency has poor sensitivity and specificity, and measurement of thyroid volume by ultrasonography is preferable (18). Thyroid ultrasonography is noninvasive, quickly done (2–3 min/individual), and feasible even in remote areas using portable equipment. However, interpretation of thyroid volume data requires valid reference criteria and age- and gender-specific references are available for 6- to 12-year-old children (3), but there are no established reference values for adults. Goitre can be classified by thyroid ultrasonography only if thyroid volume is determined by a standard method. Thyroid ultrasound examination is subjective; differences in technique can produce interobserver errors in thyroid volume as high as 26% (18).

Because more than 90% of ingested iodine is excreted in the urine, urinary iodine is an excellent indicator of recent iodine intake. Urinary iodine can be expressed as a concentration (micrograms/litre), in relation to creatinine excretion (micrograms iodine/gram creatinine), or as 24-h excretion (micrograms/day). For populations, because it is impractical to collect 24-h samples in field studies, urinary iodine can be measured in spot urine specimens from a representative sample of the target group and expressed as the median in micrograms/litre (3) (Table 3.2.3.4). However, the median urinary iodine is often misinterpreted. Individual iodine intakes and, therefore, spot urinary iodine concentrations are highly variable from day to day and a common mistake is to assume that all people with a spot urinary iodine of less than 100 μg/l are iodine deficient. To estimate iodine intakes in individuals, 24-h collections are preferable but difficult to obtain. An alternative is to use the age- and sex-adjusted iodine:creatinine ratio in adults, but this also has limitations (18). Creatinine may be unreliable for estimating daily iodine excretion from spot samples, especially in malnourished people where the creatinine concentration is low. Daily iodine intake can be extrapolated from the median urinary iodine in populations using estimates of mean 24-h urine volume and assuming an average iodine bioavailability of 92% using the following formula: urinary iodine (μg/l) × 0.0235 × body weight (kg) = daily iodine intake (4). Using this formula, a median urinary iodine of 100 μg/l in adults corresponds roughly to an average daily intake of 150 μg.

Because serum TSH is determined mainly by the level of circulating thyroid hormone, which in turn reflects iodine intake, TSH can be used as an indicator of iodine nutrition. However, in older children and adults, although serum TSH may be slightly increased by iodine deficiency, values often remain within the normal range. TSH is therefore a relatively insensitive indicator of iodine nutrition in adults (3). In contrast, TSH is a sensitive indicator of iodine status in the neonatal period. Compared to the adult, the thyroid in the newborn contains less iodine but has higher rates of iodine turnover. Particularly when iodine supply is low, maintaining high iodine turnover requires increased TSH stimulation. Serum TSH concentrations are, therefore, increased in iodine-deficient infants for the first few weeks of life, a condition termed transient newborn hypothyroidism. In areas of iodine deficiency, an increase in transient newborn hypothyroidism, indicated by more than 3% of newborn TSH values above the threshold of 5 mU/l whole blood collected 3–4 days after birth, suggests iodine deficiency in the population (3). Newborn TSH is an important measure because it reflects iodine status during a period when the developing brain is particularly sensitive to iodine deficiency.

Thyroglobulin is synthesized only in the thyroid, and is the most abundant intrathyroidal protein. In iodine sufficiency, small amounts of thyroglobulin are secreted into the circulation, and serum thyroglobulin is normally less than 10 μg/l (18). In iodine deficiency, serum thyroglobulin increases due to greater thyroid cell mass and TSH stimulation. Serum thyroglobulin is well correlated with the severity of iodine deficiency, as measured by urinary iodine. Thyroglobulin falls rapidly with iodine repletion, and is a more sensitive indicator of iodine repletion than TSH or T₄ (18).

A new assay for thyroglobulin has been developed for dried blood spots taken by a finger prick, thus simplifying collection and transport (19). In prospective studies, dried blood spot thyroglobulin has been shown to be a sensitive measure of iodine status and reflects improved thyroid function within several months after iodine repletion (19). However, several questions need to be resolved before thyroglobulin can be widely adopted as an indicator of iodine status, including the need for concurrent measurement of antithyroglobulin antibodies to avoid potential underestimation of thyroglobulin; it is unclear how prevalent antithyroglobulin antibodies are in iodine deficiency, or whether they are precipitated by iodine prophylaxis. Another limitation is large interassay variability and poor reproducibility, even with the use of standardization. This has made it difficult to establish normal ranges and/or cut-offs to distinguish severity of iodine deficiency. However, an international reference range and a reference standard for dried blood spot thyroglobulin in iodine-sufficient school-age children (4–40 μg/l) is now available (19).

Thyroid hormone concentrations (T₄ and T₃) are poor indicators of iodine intake. In iodine-deficient individuals, serum T₃ increases or remains unchanged and serum T₄ usually decreases. However, these changes are often within the normal range and make thyroid hormone levels an insensitive measure of iodine nutrition, except in areas of severe IDD (3).

In nearly all regions affected by iodine deficiency, the most effective way to control iodine deficiency is through salt iodization (3). Universal salt iodization (USI) is a term used to describe the iodization of all salt for human (food industry and household) and livestock consumption. Although the ideal, USI is rarely achieved, even in countries with successful salt iodization programmes, as food industries are often reluctant to use iodized salt and many countries do not iodize salt for livestock.

WHO/UNICEF/ICCIDD recommend that iodine is added at a level of 20–40 mg iodine/kg salt, depending on local salt intake (3). Iodine can be added to salt in the form of potassium iodide (KI) or potassium iodate (KIO₃). Because KIO₃ has higher stability than KI in the presence of salt impurities, humidity, and porous packaging, it is the recommended form in tropical countries and those with low-grade salt. Iodine is usually added after the salt has been dried. Two techniques are used: (1) the wet method, where a solution of KIO₃ is dripped or sprayed at a regular rate onto salt passing by on a conveyor belt, or (2) the dry method, where KI or KIO₃ powder is sprinkled over the dry salt. Optimally, packaging should be in low-density polyethylene bags, as high humidity combined with porous packing may result in up to 90% loss of iodine after 1 year of storage in high-density polyethylene bags.

Salt iodization remains the most cost-effective way of delivering iodine and of improving cognition in iodine-deficient populations (11, 20). Worldwide, the annual costs of salt iodization are estimated at US$0.02–0.05 per child covered, and the costs per child death averted are US$1000 and per disability-adjusted life year (DALY) gained are US$34–36 (Fig. 3.2.3.3) (11). Looked at in another way, before widespread salt iodization, the annual potential losses attributable to iodine deficiency in the developing world have been estimated to be US$35.7 billion as compared with an estimated US$0.5 billion annual cost for salt iodization, i.e. a 70:1 benefit:cost ratio (1). The World Bank (20) strongly recommends that governments invest in micronutrient programmes, including salt iodization, to promote development, and concludes: ‘Probably no other technology offers as large an opportunity to improve lives at such low cost and in such a short time.’

In some regions, iodization of salt may not be practical for control of iodine deficiency, at least in the short term. This may occur in remote areas where communications are poor or where there are numerous small-scale salt producers. In these areas, iodized oil supplements can be used (3). Iodized oil is prepared by esterification of the unsaturated fatty acids in seed or vegetable oils and addition of iodine to the double bonds. It can be given orally or by intramuscular injection (3). The intramuscular route has a longer duration of action, but oral administration is more common because it is simpler. Usual dosages are 200–400 mg iodine/year and it is often targeted to women of child-bearing age, pregnant women, and children (3) (Table 3.2.3.5). Its disadvantages are an uneven level of iodine in the body over time and the need for direct contact with individuals with the accompanying increased programme costs.

Iodine can also be given as KI or KIO₃ in drops or tablets. Single oral doses of KI monthly (30 mg) or biweekly (8 mg) can provide adequate iodine for school-age children (21). Lugol’s iodine, containing approximately 6 mg iodine/drop, and similar preparations are often available as antiseptics in rural dispensaries in developing countries and offer another simple way to deliver iodine locally. In countries or regions where a salt iodization programme covers at least 90% of households, has been sustained for at least 2 years, and the median urinary iodine indicates iodine sufficiency (Table 3.2.3.4), pregnant and lactating women do not need iodine supplementation (3). In iodine-deficient countries or regions that have weak iodized salt distribution, supplements should be given to pregnant women, lactating women, and infants, according to the guidelines in Table 3.2.3.5 (3).

Balance studies in healthy preterm infants have suggested iodine intakes of at least 30 μg/kg body weight per day are required to maintain positive balance, and experts generally recommend iodine intakes of 30–60 μg/kg per day for this group (22, 23). Formula milks for preterm infants contain 20–170 μg iodine/l, and, depending on the dietary iodine intake of the mother, breast milk generally contains 50–150 μg/l. Thus, particularly during the first postnatal weeks when feed volumes are often low, enterally fed preterm infants may not achieve the recommended intake of iodine (23). US and European clinical nutrition societies recommend parenteral iodine intakes of 1 μg/kg body weight per day (24), far below fetal accretion rates. This conservative recommendation assumes parenterally fed preterm infants will absorb iodine through the skin from topical iodinated disinfectants, and also receive small amounts of adventitious iodine in other infusions. Frequent use of iodinated antiseptics in infants can result in transcutaneous absorption of at least 100 μg iodine/day, iodine excess, and neonatal hypothyroidism.

Because of concerns over possible iodine excess, use of iodinated antiseptics in infants may be decreasing, putting infants at risk of iodine deficiency (25). If parentally fed preterm infants are not exposed to adventitious sources of iodine, they may receive only 1–3 μg iodine/kg body weight per day, and be in negative iodine balance during the first few postnatal weeks (23). Several authors have argued that iodine deficiency should be avoided during this period because it may transiently lower thyroid hormone levels in the first weeks of life (23, 25), and transient hypothyroxinaemia in preterm infants has been linked to impaired neurodevelopment (26). However, a recent review concluded that the available data are insufficient to support supplementation of preterm infants with iodine (26).

A daily dose of 1 μg iodine/kg body weight is recommended for children receiving parenteral nutrition (24), and parenteral trace element additives containing iodine are available for paediatric use. An example is Peditrace solution (Fresenius Kabi, Bad Homburg, Germany), which contains KI (1.3 μg/ml KI equivalent to 1 μg iodide/ml); the recommended dosage for infants and children weighing 15 kg or less, and 2 days old or older, is 1 ml/kg body weight per day, and the recommended daily dose is 15 ml to children weighing more than 15 kg.

Commercially available products for enteral nutrition generally supply 75–110 μg iodine/serving. A recent technical review recommended iodine intakes of 70–140 μg/day during parenteral nutrition (27). Although most parenteral nutrition formulations do not contain iodine, deficiency is not likely to occur because of cutaneous absorption from iodine-containing disinfectants and other adventitious sources of iodine. Iodine deficiency symptoms have not been reported with inhospital intravenous nutrition support. It is likely that thyroidal iodine stores are often adequate to meet the needs of patients requiring total parenteral nutrition for less than 3 months; in iodine-sufficient adults, thyroidal iodine content may be as high as 15–20 mg (1). For these reasons, supplemental iodine is not routinely recommended for patients receiving total parenteral nutrition (28). If needed, intravenous sodium iodide solutions are available. For example, Iodopen (APP Pharmaceuticals, Schaumberg, IL, USA) contains 100 μg iodine/ml, and the usual adult dosage for prophylaxis or treatment of iodine deficiency in adults is 1–2 μg iodine/kg body weight per day; for children and pregnant or lactating women, the recommended dosage is 2–3 μg iodine/kg per day.

Prospective data on the epidemiology of thyroid disorders caused by changes in iodine intake is scarce. In areas of iodine sufficiency, healthy individuals are remarkably tolerant to iodine intakes of up to 1 mg/day, as the thyroid is able to adjust to a wide range of intakes to regulate the synthesis and release of thyroid hormones. European (29) and US (4) expert committees have recommended tolerable upper intake levels for iodine, but caution that individuals with chronic iodine deficiency may respond adversely to intakes lower than these. In monitoring populations consuming iodized salt, the WHO/UNICEF/ICCIDD recommendations for the median urinary iodine that indicates more than adequate and excess iodine intake (3) are shown in Table 3.2.3.4.

To investigate the effects of iodine intake on thyroid disorders in China, a 5-year prospective community-based survey was carried out in three rural Chinese communities with mildly deficient, more than adequate (previously mild iodine deficiency corrected by iodized salt), and excessive iodine intake from environmental sources; the median urinary iodine was 88, 214, and 634 μg/l, respectively. For the three communities, the cumulative incidence of hyperthyroidism was 1.4, 0.9, and 0.8%; of overt hypothyroidism, 0.2, 0.5, and 0.3%; of subclinical hypothyroidism, 0.2, 2.6, and 2.9%; and of autoimmune thyroiditis, 0.2, 1.0, and 1.3%, respectively. In most individuals, these last two disorders were not sustained (30).

Denmark has documented the pattern of thyroid disease after careful introduction of iodized salt. New cases of overt hypothyroidism were identified in two areas of Denmark with previously moderate and mild iodine deficiency (Aalborg, median urinary iodine = 45 μg/l, and Copenhagen, median urinary iodine = 61 μg/l) before and for the first 7 years after introduction of a national programme of salt iodization. The overall incidence rate of hypothyroidism modestly increased during the study period: baseline 38.3/100 000 per year; after salt iodization 47.2/100 000 (versus baseline, relative risk = 1.23; 95% CI = 1.07 to 1.42). There was a geographical difference because hypothyroidism increased only in the area with previous moderate iodine deficiency. The increase occurred in young and middle-aged adults. Similarly, new cases of overt hyperthyroidism in these two areas of Denmark before and for the first 6 years after iodine fortification were identified. The overall incidence rate of hyperthyroidism increased (baseline 102.8/100 000 per year; after salt iodization 138.7/100 000). Hyperthyroidism increased in both sexes and in all age groups, but many of the new cases were observed in young people—the increase was highest in adults aged 20–39 years—and were presumably of autoimmune origin (30).

The overall incidence of differentiated thyroid carcinoma in populations does not appear to be influenced by iodine intake. The distribution of the subtypes of thyroid carcinoma is related to iodine intake (30); in areas of higher iodine intake, there appear to be fewer of the more aggressive follicular and anaplastic carcinomas, but more papillary carcinomas. When iodine prophylaxis is introduced in populations, there may be an increase in the ratio of papillary to follicular carcinoma, and this shift towards less malignant types of thyroid cancer, as well as a lower radiation dose to the thyroid in case of nuclear fallout, are benefits of the correction of mild-to-moderate iodine deficiency.

Globally, two billion individuals have inadequate iodine intake. Iodine deficiency has multiple adverse effects on growth and development due to inadequate thyroid hormone production; these effects are termed the IDD. The most serious adverse effect of iodine deficiency is damage to the fetus, and iodine deficiency remains one of the most common causes of preventable mental impairment worldwide. Four methods are generally recommended for assessment of iodine nutrition: (1) urinary iodine concentration, (2) the goitre rate, (3) blood concentration of TSH, and (4) blood concentration of thyroglobulin. Iodine repletion in pregnant women reduces fetal and perinatal mortality and improves motor and cognitive performance of the offspring. In children born and raised in areas of iodine deficiency, cognitive impairment is at least partially reversible by iodine repletion. Iodine repletion also increases circulating IGF and improves somatic growth in children. In nearly all countries, the best strategy to control iodine deficiency is salt iodization, one of the most cost-effective ways to contribute to economic and social development. When salt iodization is not possible, iodine supplements can be targeted to vulnerable groups. Daily iodine requirements in adult patients receiving total enteral or parenteral nutrition are estimated to be 70–150 μg. Although most parenteral nutrition formulations do not contain iodine, deficiency is not likely to occur because of cutaneous absorption from iodine-containing disinfectants and other adventitious sources of iodine. Because of concerns over possible iodine excess, use of iodinated antiseptics in infants may be decreasing, potentially increasing the risk of iodine deficiency in this group. However, the available data are insufficient to support supplementation of preterm infants with iodine. Iodine intakes up to 1 mg/day are well tolerated by most adults, as the thyroid is able to adjust to a wide range of intakes and to regulate the synthesis and release of thyroid hormones. The introduction of iodine to regions of chronic IDD may transiently increase the incidence of thyroid disorders, but overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency.