Iodine Deficiency Disorders (IDD): Causes, Effects, and Epidemiology

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Iodine Deficiency Disorders
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Menon K., and Skeaff S. (2016) Iodine: Iodine Deficiency Disorders (IDD). In: Caballero, B., Finglas, P., and
Toldrá, F. (eds.) The Encyclopedia of Food and Health vol. 3, pp. 437-443. Oxford: Academic Press.
© 2016 Elsevier Ltd. All rights reserved.

Iodine: Iodine Deficiency Disorders (IDD)
K Menon and S Skeaff, University of Otago, Dunedin, New Zealand
ã2016 Elsevier Ltd. All rights reserved.
Introduction
Iodine (I) is an essential anionic trace element and occurs
naturally in the environment as iodide found in seawater and
soils. The distribution of iodine varies widely in the Earth’s
crust. The soils of mountainous and volcanic areas have low
iodine content. The soil iodine content directly determines the
iodine content of foods and water and indirectly determines
the iodine status of human and animals in the region. Humans
derive iodine through their diets, 90% via food and 10%
from water. Rich sources of dietary iodine include seafood and
seaweeds due to high concentrations of iodine in the ocean,
good sources include eggs and dairy products, while trace
amounts of iodine are present in grains and vegetables. Addi-
tionally, foods such as breads, fish sauce, salt, and water can be
fortified with iodine. The use of iodized salt is widely recom-
mended for populations inhabiting endemically iodine-
deficient regions. Dietary iodide in food is absorbed in the
stomach and duodenum and enters the circulation where it is
cleared by the thyroid and kidney. The thyroidal uptake of
iodine in the blood depends on iodine status, with 10% in
iodine-sufficient and >80% uptake in iodine-deficient
individuals.
The adult human body contains 15–50 mg of iodine with
two-thirds found in the thyroid gland and the remaining one-
third in the circulating blood, primarily contained in the thy-
roid hormones (TH). Iodine is an essential component of the
TH, which include the prohormone, thyroxine (T
4
), and the
active hormone, 3,5,30-tri-iodothyronine (T
3
). T
4
contains four
iodine atoms with a half-life of 5 days, while the bioactive and
more potent T
3
contains three iodine atoms and has a half-life
of 1.5–3 days. TH regulate a wide variety of physiological
processes such as protein synthesis and enzymatic activities;
cell differentiation, growth, and development of different tis-
sues, especially of the central nervous system; maturation; and
energy production and cellular respiration, which influences
the metabolic rate of the body. The main organs influenced by
TH are the developing brain, muscle, heart, pituitary, and
kidney. The human body regulates TH concentrations through
thyroid-stimulating hormone (TSH) secreted by the pituitary
gland via a negative auto-feedback mechanism. In addition,
TSH influences iodine metabolism through uptake of iodine
by the thyroid and synthesis and secretion of TH.
Iodine requirements vary throughout the life cycle. The
World Health Organization (WHO)-, United Nations Children’s
Fund (UNICEF)-, and the International Council for Iodine Defi-
ciency Disorders (ICCIDD)-, now known as the Iodine Global
Network (IGN)-recommended iodine intakes for different stages
of the life cycle are outlined in Table 1. The requirement
for iodine is highest in pregnant and lactating women. In
pregnancy, iodine requirements escalate due to increased pro-
duction of TH and transfer of iodine to the fetus and, in lactating
women, to support the excretion of iodine in breast milk.
A constant low daily intake of iodine below the requirement
leads to chronic iodine deficiency (ID), which decreases TH
secretion and, eventually, impairs normal thyroid function;
this is the most important cause of ID. Low iodine content in
the diet is caused by environmental factors such as glaciation,
floods, and erosion resulting in the depletion of soil iodine
content. Consequently, locally grown foods in these regions
contain insufficient iodine for human beings and animals.
Also, some foods contain a variety of substances or goitrogens
that interfere with thyroidal iodine uptake (Table 2). Industrial
pollutants such as perchlorate are competitive inhibitors of
thyroidal iodine uptake. Cigarette smoking increases serum
thiocyanate levels that compete with iodine for uptake into
both the thyroid and the secretory epithelium of the lactating
breast. When iodine intakes are adequate, goitrogens are nor-
mally not harmful; however, in the presence of ID, goitrogens
might exacerbate the clinical effects of ID. Further, coexisting
deficiencies of selenium, iron, and vitamin A aggravate the
effects of ID either via impairing activities of mineral-dependent
enzymes such as selenium-dependent deiodinases and iron-
dependent thyroperoxidase or by vitamin A-mediated suppres-
sion of the pituitary TSHbgene. Thus, chronic insufficient
intakes of iodine eventually precipitate ID in human beings.
Epidemiology
ID is the most common cause of preventable mental impair-
ment and affects about 2 billion people worldwide; it is a
major public health challenge. ID is widespread in both devel-
oped and developing countries. According to ICCIDD, 29.8%
of school-age children worldwide are iodine-insufficient and
more than a half of these children reside in two regions: 78
million in Southeast Asia and 58 million in Africa. The pro-
portion of school-age children with insufficient iodine intake
is highest in Europe (43.9%; 30.5 million), followed by Africa
(39.5%; 58.1 million). There has been a decline in the global
prevalence of ID in school-age children from 36.5% in 2003 to
29.8% in 2011, the overall progress being marginal in Africa.
In 2011, ICCIDD classified 32 countries with ID (9 moderately
with ID and 23 with mild ID), 69 countries as iodine adequate,
36 as more than adequate, and 11 as excessive. Globally, there
is a dearth of nationally representative prevalence estimates of
ID in pregnant and lactating women.
Iodine Deficiency Disorders
ID has several adverse effects on human beings. As coined by
Hetzel in 1983, the term iodine deficiency disorders (IDDs)
collectively refers to the adverse effects of ID on growth and
development in human and animal populations (Table 3).
Chronic insufficient iodine intake stimulates the production
Encyclopedia of Food and Health http://dx.doi.org/10.1016/B978-0-12-384947-2.00399-8 437
The Encyclopedia of Food and Health, (2016), vol. 3, pp. 437-443
Author's personal copy

of TSH from the pituitary gland. A series of TSH-mediated
adaptations occur in the thyroid gland before the onset of
goiter. TSH stimulates thyroidal uptake of iodide, enhances
the breakdown of thyroglobulin (Tg), and promotes secretion
of T
3
and conversion of T
4
to T
3
in peripheral tissues to con-
serve the number of iodine atoms used. The serum Tg concen-
tration increases due to TSH stimulation. Increased iodide
uptake by the thyroid leads to decreased renal clearance, thus
a fall in the urinary iodine concentration (UIC). Further, the
hyperplasia (i.e., increase in the number of cells) and hyper-
trophy (i.e., increase in the size of cells) of the thyroid cells
enhance the use of available iodine efficiently to synthesize TH
and underpin the enlargement of the thyroid gland or goiter.
Goiter is the classic and most visible effect of IDD. In chronic
ID, the initial diffused homogeneous enlargement of the thy-
roid gland gradually results in the formation of thyroid nod-
ules. Women over 50 years with chronic ID have a high
prevalence of multinodular goiter. IDD affects all ages of the
population in manifold ways. Goiter, physical sluggishness,
growth retardation, and decreased productivity are the well-
known adverse outcomes of ID.
WHO/UNICEF/ICCIDD recommends the use of UIC to
assess the iodine nutrition of children >2 years old, adults,
Table 2 Goitrogens and their mechanisms
Goitrogens Mechanism of action
Foods
Cassava, lima beans, linseed,
sorghum, sweet potato
Contain cyanogenic glucosides;
they are metabolized to
thiocyanates that compete with
iodine for thyroidal uptake
Cruciferous vegetables such as
cabbage, kale, cauliflower,
broccoli, turnips, rapeseed
Contain glucosinolates; metabolites
compete with iodine for thyroidal
uptake
Soy, millet Flavonoids impair thyroid
peroxidase activity
Industrial pollutants
Perchlorate Competitive inhibitor of the
sodium/iodine symporter,
decreasing iodine transport into
the thyroid
Others (e.g., disulfides from coal
processes)
Reduce thyroidal iodine uptake
Smoking An important goitrogen; smoking
during breastfeeding is
associated with reduced iodine
concentrations in breast milk;
high serum concentration of
thiocyanate due to smoking
might compete with iodine for
active transport into the secretory
epithelium of the lactating breast
Nutrients
Selenium deficiency Accumulated peroxides might
damage the thyroid, and
deiodinase deficiency impairs
thyroid hormone synthesis
Iron deficiency Reduces heme-dependent
thyroperoxidase activity in the
thyroid and might blunt the
efficacy of iodine prophylaxis
Vitamin A deficiency Increases TSH stimulation and
goiter through decreased vitamin
A-mediated suppression of the
pituitary TSHbgene
TSH, thyroid-stimulating hormone
Source: Zimmermann, M. B., Jooste, P. L., and Pandav, C. S. (2008) Iodine-deficiency
disorders. Lancet.372: 1251–1262.
Table 1 Recommended iodine intake
Age or population group
Recommended iodine intake
(mg day
1
)
Children 0–5 years 90
Children 6–12 years 120
Children >12 years and
adults
150
Pregnant women 250
Lactating women 250
Source: WHO/UNICEF/ICCIDD (2007). Assessment of iodine deficiency disorders and
monitoring their elimination. Report of a joint WHO/UNICEF/ICCIDD consultation.
Geneva: WHO
Table 3 Spectrum of iodine deficiency disorders
Age groups Health consequences of iodine deficiency
All ages Goiter, including toxic nodular goiter
Increased occurrence of hypothyroidism in
moderate-to-severe iodine deficiency; decreased
occurrence of hypothyroidism in mild-to-moderate
iodine deficiency
Increased susceptibility of the thyroid gland to
damage and thyroid cancer from iodine radio
isotopes (e.g., from radioactive fallout)
Fetus Abortion
Stillbirth
Congenital abnormalities
Perinatal mortality
Psychomotor defects
Neonate Infant mortality
Endemic cretinism
Impaired physical growth
Neonatal hypothyroidism
Child and
adolescent
Impaired mental function
Delayed physical development
Adults Impaired mental function
Lower intelligence quotient and cognitive index
Iodine-induced hyperthyroidism, goiter
Overall, moderate-to-severe iodine deficiency
causes subtle but widespread adverse effects in a
population secondary to hypothyroidism, including
decreased educability, apathy, and reduced work
productivity, resulting in impaired social and
economic development
Pregnant
women
Subclinical hypothyroidism
Poor pregnancy outcomes
Premature delivery
Source: WHO/UNICEF/ICCIDD (2007). Assessment of iodine deficiency disorders and
monitoring their elimination. Report of a joint WHO/UNICEF/ICCIDD consultation.
Geneva: WHO.
438 Iodine: Iodine Deficiency Disorders (IDD)
The Encyclopedia of Food and Health, (2016), vol. 3, pp. 437-443
Author's personal copy

pregnant women, and lactating women. The use of UIC centers
on the fact that 90% of ingested iodine is excreted in the
urine. Although useful to estimate recent dietary intake, the
collection of 24 h urine samples is cumbersome in the field.
Thus, to facilitate the process of sample collection, WHO/
UNICEF/ICCIDD recommends the use of nonfasting casual
or spot urine samples from a representative population. The
median UIC, expressed as mgl
1
, determined in spot urine
samples are only useful as a population estimate and cannot
be used to assess iodine status in individuals (Table 4). IDD is
considered as a public health problem when a population has
median UIC<100 mgl
1
in a representative sample of school-
age children; the median UIC of the sample can also be used to
categorize the degree of ID, which can be mild, moderate, or
severe as shown in Table 4. UIC has only been validated in
school children although it is used for adults. Given the higher
dietary iodine requirements of pregnant women, a median
UIC between 150 and 250 mgl
1
is used to indicate adequate
iodine status in this group.
Recently, the use of Tg concentrations in school-age chil-
dren to assess iodine status has been proposed to assess iodine
status in a population. A median Tg concentration >13 mgl
1
and/or >3% of Tg values >40 mgl
1
indicates ID in the pop-
ulation. In pregnant women, TH and TSH are used to deter-
mine the optimum thyroid function, which may be used as a
surrogate marker for ID; however, the normal reference ranges
of TH and TSH are wide; thus, these measures are considered
insensitive in areas of moderate-to-mild ID. The epidemiolog-
ical criteria for the assessment of severity of ID based on the
TSH concentration in neonates and total goiter rate in school-
age children are extensively used in some countries (Table 5).
IDD in Pregnancy, Lactation, and Infancy
ID during pregnancy has a deleterious impact on the fetus and
the mother. Healthy women from iodine-sufficient areas have
about 15–20 mg of iodine stores in the thyroid. There is a 50%
increase in iodine requirements in pregnant women to produce
adequate TH that meets maternal and fetal needs. Additional
iodine is needed to maintain maternal TH concentration and
transfer TH to the fetus before the fetal thyroid begins to func-
tion in the second trimester (around 16–20 weeks of gestation),
transfer iodine to the fetus during late gestation, and maintain
iodine levels in response to increased renal iodine clearance by
the mother. Until the second semester, maternal T
4
serves as the
only source of TH for the developing fetus. Pregnant women in
chronic ID areas have little iodine stored in their thyroid. In
such situations, poor iodine intake may lead to the onset of ID
in the mother, and subsequently the fetus. Despite mild-to-
moderate maternal ID during the first trimester of pregnancy,
maternal TH concentrations typically remain within the normal
reference range due to suppression of TSH secretion by the
human chorionic gonadotrophin in response to an increase in
maternal T
4
(i.e., maternal euthyroidism or normal thyroid
function) and the physiological adaptations of the thyroid
gland in response to ID. Regardless of the maternal euthyroid-
ism, the fetus is exposed to hypothyroxinemia (i.e., low T
4
in the
blood). Consequently, specific parts of the developing fetal
brain suffer from a hypothyroxinemic insult, which impairs
neurodevelopment. In the second trimester, the fetal thyroid
begins to function but is not fully matured and cannot auto-
regulate the mechanisms needed to normalize TH secretion.
This may lead to a surge in fetal TSH production and subse-
quently fetal hypothyroidism.
Normal concentrations of maternal TH are essential for
fetal brain growth. TH influence two phases of brain growth;
Table 4 WHO epidemiological criteria for assessment of iodine
nutrition in a population based on median or range of UIC
Median UIC
(mgl
1
)
Iodine
intake Iodine nutrition
School-aged children
<20 Insufficient Severe iodine deficiency
20–49 Insufficient Moderate iodine deficiency
50–99 Insufficient Mild iodine deficiency
100–199 Adequate Optimum
200–299 More than
adequate
Risk of iodine-induced hyperthyroidism
in susceptible groups
>300 Excessive Risk of adverse health consequences
(iodine-induced hyperthyroidism,
autoimmune thyroid disease)
Pregnant women
<150 Insufficient
150–249 Adequate
250–499 More than
adequate
500
a
Excessive
Lactating women
b
<100 Insufficient
100 Adequate
Children <2years of age
<100 Insufficient
100 Adequate
a
The term excessive means in excess of the amount needed to prevent and control
iodine deficiency.
b
In lactating women, the numbers for median urinary iodine are lower than the iodine
requirements, because of the iodine excreted in breast milk.
Source: WHO/UNICEF/ICCIDD (2007). Assessment of iodine deficiency disorders and
monitoring their elimination. Report of a joint WHO/UNICEF/ICCIDD consultation.
Geneva: WHO.
Table 5 WHO epidemiological criteria for assessment of severity of
iodine deficiency in populations
Criteria None Mild Moderate Severe
Total goiter rate (%) 0–4.9 5–19.9 20–29.9 >30
Neonatal TSH >5 mlU ml
1
(%)
<3 3–20 20–40 >40
Classification of goiter by palpation
Grade 0 No visible or palpable goiter
Grade 1 A goiter that is palpable but not visible
when the neck is in the normal position
Grade 2 A palpable, visible, and enlarged thyroid
when the neck is in the normal position
TSH, thyroid-stimulating hormone
Source: WHO/UNICEF/ICCIDD (2007). Assessment of iodine deficiency disorders and
monitoring their elimination. Report of a joint WHO/UNICEF/ICCIDD consultation.
Geneva: WHO
Iodine: Iodine Deficiency Disorders (IDD) 439
The Encyclopedia of Food and Health, (2016), vol. 3, pp. 437-443
Author's personal copy