Symposium: Clinical Nutrition in Developing Countries:
Toward the Application of
Contemporary Concepts and Technology
Iodine Deficiency Disorders: Contemporary
Scientific Issues1'2
GLEN F. MABERLY
Center for International Health, Emory School of Public Health, Atlanta,
ABSTRACT Iodine deficiency is the leading cause of
preventable intellectual impairment and is associated
with a spectrum of neurologic and developmental
pathology. More than one billion people are at risk. The
developing fetus, newborn, and young child are the most
susceptible to the effects of an iodine-deficient diet. If
intervention is not initiated in a timely fashion, the
pathophysiologic abnormalities become resistant to
treatment and permanent intellectual, neurologic, and
somatic deficits result. The technology of iodine defi
ciency intervention is well established. Iodized salt, the
preferred method, is easy to produce, administer in
physiologic doses, and is cost effective. The distribution
of iodized salt and social marketing are key to a suc
cessful iodine deficiency elimination program. In remote
regions, iodized oil is a useful interim intervention.
However, it is clear that technology is not enough. Any
national effort to eliminate iodine deficiency must extend
far beyond the Ministry of Health. The program will re
quire the full participation of a range of national
government ministries and agencies and the full support
and participation of local or regional governments. J.
Nutr. 124: 1473S-1478S, 1994.
INDEXING KEY WORDS:
•cretinism •intellectual impairment
•iodine deficiency •public health
•thyroid hormone
It is estimated that more than 1 billion people,
concentrated primarily in less developed countries,
are unable to consume adequate levels of iodine. Only
during the last decade has it been recognized that
iodine deficiency disorders are the leading cause of
intellectual impairment (1, 2). An adequate intake of
iodine is of immense importance to global de
velopment. Iodine deficiency on this magnitude
means that investments in economic development
and education can not achieve their desired outcomes
unless this problem is addressed. The prevention of
this deficiency is one of the most important
0022-3166/94 $3.00 ©1994 American Institute of Nutrition.
1473S
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GA 30329
achievable international health goals of the decade,
conceivably exceeding the impact of the global eradi
cation of smallpox (3). Although prevention of iodine
deficiency disorders is no panacea for such ills of the
Third World as famine, acquired immune deficiency
syndrome (AIDS), political strife and poverty, the
normal intellectual functioning and well being as
sociated with iodine sufficiency may be essential to
the long term resolution of these national and
regional problems.
Programs to eliminate iodine deficiency cannot be
separated from other national nutrition programs
such as food production, food security, and the elimi
nation of protein-energy malnutrition. In fact much
attention in the past has been directed towards an
adequate intake of protein or calories. It is clear that
attention to dietary quality is of tantamount impor
tance (3). The elimination of iodine deficiency dis
orders cannot be isolated from other major public
health problems or development issues. Success can
only come through the combined efforts of technical
experts who have the scientific knowledge and tech
nological know-how, food producers and marketers
who are able to create demand and deliver improved
products to people, and the policy makers who
possess the power to make decisions regarding public
health interventions. The relative simplicity and low
'Presented as part of the symposium "Clinical Nutrition in
Developing Countries: Toward the Application of Contemporary
Concepts and Technology" given at the Experimental Biology '93
meeting, New Orleans, LA, March 31, 1993. This symposium was
sponsored by the American Institute of Nutrition and the American
Society for Clinical Nutrition. Guest editor for this symposium
was Noel W. Solomons, Center for Studies of Sensory Impairment,
Aging and Metabolism, Guatemala City, Guatemala.
This presentation was made possible by support from the
Office of Nutrition, Bureau for Research and Development, U.S.
Agency for International Development, under Cooperative
Agreement No. HRN-5110-A-00-2048-00.
1474S MABERLY
cost of the interventions, and the enormous potential
benefit to nations that are successful may capture the
imagination of policy makers and help raise other
nutrition and health issues higher on the scale of
national development priorities (4).
This article reviews the nature and magnitude of
the problem of iodine deficiency disorders and dis
cusses strategies that can be adopted by agencies and
countries who are committed to its sustained elimi
nation.
HISTORICAL CONSIDERATIONS
The historical record of goiter dates back to about
2700 BC with a reference by the Chinese Emperor
Shen-Nung about the use of seaweed to treat goiter.
As early as 200-300 AD goiter appears in art work
present in sculptures of Buddha and his disciples. The
association of goiter and cretinism is alluded to in
drawings from the 13th century and is first noted by
Paracelsus in the early 16th century. Surgery for
goiter was performed at the early medical schools in
Salerno (1170), Montpellier (1240), and Padua (1252).
Renaissance art also contains many examples of
goiter and is found in paintings by well known artists
including Rubens, Weyden, and Dürer.However, it is
not until the 17th century that the thyroid gland is
first described (5).
In the 18th century the word cretin appears in print
for the first time and is defined as "an imbecile who is
deaf and dumb with a goiter hanging down to the
waist". The 19th century was important in the
history of iodine deficiency. In the 1820s, iodine was
identified in seaweed and in salt from a mine in
Antioquia. It was in 1846 that Prévostand Maffoni
first hypothesized that goiter was due to iodine defi
ciency. The 19th century yielded one of the first
national goiter surveys, commissioned by King Carlo
Alberto of Sardinia (Sardinia included the provinces of
Savoy, Nice, Piedmont, Genoa, and the Island of
Sardinia) in 1848. The survey revealed 370,403
persons with goiter and 120,000 cretins or idiots in
France with an estimated total population of 36
million. The initial attempts to use iodine prepara
tions to treat goiter met opposition after symptoms of
thyroid toxicity were identified in large numbers of
patients because the dose was too high. Initially
thought to serve a humidifying role in the larynx, it is
not until the late 19th century that iodine was iden
tified in the thyroid gland and the thyroid's role as an
endocrine organ postulated (6).
In the 19th century David Marine stated that 'en
demic goiter is the easiest known disease to prevent'.
The first large scale trials with iodine were performed
by Marine and Kimball (1922) in Ohio. In 1924, the
first mass prophylaxis of goiter with iodized salt was
carried out in Michigan (7). The prevalence of goiter
and cretinism was high in the mountainous regions of
Europe and seemed to decrease precipitously after the
introduction of iodized salt. Also contributing to the
decline in the prevalence of goiter was the impor
tation of foods from outside the area of iodine defi
cient soil (6).
Iodine deficiency disorders have been eliminated
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for more than 40 years in several countries including
the USA, England, Switzerland, New Zealand and
Australia. Iodine deficiency disorders were severely
endemic in Bhutan 5 years ago, and, through salt iodi-
zation and iodized oil injections, now has been vir
tually eliminated. Similarly, Ecuador and Bolivia are
close to elimination of iodine deficiency disorders. On
the other hand, Europe, which was once considered
nonendemic, has once again been reported to have a
dangerous iodine deficiency disorders problem (18).
NATURE OF THE PROBLEM
Central nervous system development depends on
an adequate supply of thyroid hormone, which re
quires iodine for biosynthesis. Thus, iodine is an es
sential micronutrient for normal intellectual de
velopment and functioning. Without the biologically
required micro-quantities provided in the diet, mild
to severe intellectual impairment and mental
retardation may occur (9, 10).
Endemic cretinism is the most severe
manifestation of the lack of maternal and fetal
thyroid hormone arising from severe dietary iodine
deficiency. The hallmarks of endemic cretinism in
clude mental retardation and a brain disorder best
described as showing pyramidal signs in an upper
limb distribution and extrapyramidal signs. These
subjects have a diagnostic gait, which is not only
related to the neurological disorder but contributed to
by joint laxity and deformity. Other frequently en
countered clinical features include squinting,
deafness, and primitive brain reflexes. In some popu
lations there is additional manifestation of endemic
cretinism resulting from continuing postnatal thyroid
hormone deficiency. This results in the additional
clinical features of hypothyroidism: severe stunting of
growth; skeletal retardation,- and sexual immaturity.
A prevalence of cretinism from 3-15% is commonly
found in severely affected rural populations in many
endemias around the world (11, 12).
There is good evidence from community-based as
sessments and iodine intervention trials that iodine
deficiency disorders can leave entire populations with
a subnormal average intelligence quotient and im
paired motor functions. Mild iodine deficiency has
been reported to reduce IQ by 10-15% (13). Recently,
Bleichrot and Born reported results of a meta-analysis
of research on iodine and its relationship to cognitive
 SYMPOSIUM: CLINICAL NUTRITION
development (14). From the 18 publications suitable
for study they reported a large negative effect on the
cognitive function of subjects born in iodine deficient
situations compared with controls (d = 0.9). The mean
IQ scores in the iodine deficient group and the non-
iodine deficient group are 0.9 SD, or 13.5 IQ points
apart. In other words, a child with an average score in
the noniodine-deficient group scores higher than 82%
of the children from the iodine deficient group. Other
consequences of iodine deficiency include increased
stillbirths and increased perinatal and infant mor
tality.
PUBLIC HEALTH IMPORTANCE
In 1991 using the best available data from many
sources including member states and other interna
tional and bilateral organizations, the World Health
Organization estimated that 20% of humanity live in
areas at risk of iodine deficiency. The at risk and
affected persons live in 95 countries (15). The preva
lence and morbidity of iodine deficiency disorders
throughout the world requires further elucidation. It
is only recently that scientists are beginning to ap
preciate that the effects of iodine deficiency may be
insidious, causing mild to moderate intellectual im
pairment without the overt clinical signs of iodine
deficiency disorders. The development of a new sen
sitive TSH whole blood filter paper based assay has
detected prevalence of mild to moderately elevated
TSH of -20-40% among newborns in China and In
donesia (16). These findings are consistent with wide
spread iodine deficiency disorders and represent a
threat to the normal neurologic and somatic de
velopment of these infants. In fact, developing fetuses
and infants up to the age of 2 y are most susceptible
to the effects of iodine deficiency disorders. Although
iodine deficiency disorders is 100% preventable, most
of its effects are irreversible after the second year of
life (1).
The full scope of iodine deficiency disorders mor
bidity is entirely preventable with the administration
of the appropriate dose of iodine. The exposure or risk
factor for iodine deficiency disorders is soil that lacks
sufficient iodine and as such represents a regional
exposure. Iodine deficiency disorders has been noted
to affect not only whole families but large proportions
of villagers because the regions in which it occurs are
often remote and depend exclusively on locally
produced food. While the regional nature of the ex
posure may result in a high percentage of family
members or village inhabitants being affected, it also
means that intervention can be targeted regionally
and efforts focused.
The development of strategic plans for the elimi
nation of iodine deficiency disorders is critical to the
success of the process. This is relevant to activities at
IN DEVELOPING COUNTRIES 1475S
the global, national, provincial, county or community
level. The planning process needs to involve key
change agents and be adaptable to the situation where
they will be introduced. Any such plan can be broken
down to its components. However all components are
highly linked and their relationships to each other are
as important as the elements themselves. These key
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elements include: Õ)advocacy; 2} interventions,- 3)
communications and social marketing; and 4} evalu
ation. These components are closely linked and re
quire the support and perspectives of good
management and benefit from ongoing applied re
search and development (4).
ADVOCACY
Since the mid 1980s, The International Council for
the Control of Iodine Deficiency Disorders (ICCIDD)
has been instrumental in focusing the world's at
tention on iodine deficiency disorders. The ICCIDD,
founded by Basil Hetzel, has pioneered in the areas of
advocacy and research and development for iodine
deficiency disorders elimination. The board met for
the first time in Katmandu, Nepal, and since then has
met annually or bi-annually and has been active in
advocating the global elimination of iodine deficiency
disorders through international, regional and national
forums and training events, technical forums, publica
tions and consultations (17).
Elimination of micronutrient malnutrition, in
cluding iodine deficiency disorders, is on the global
agenda. Seventy-one heads of state and senior policy
makers from 80 other countries attended The World
Summit for Children in September, 1990 and en
dorsed The World Declaration and 1990-2000 Plan of
Action on the Survival, Protection and Development
of Children (18). The plan stated that the world is in a
position to "overcome the worst forms of mal
nutrition ... to halve protein-energy malnutrition, vir
tually eliminate iodine deficiency disorders, virtually
eliminate vitamin-A deficiency and its consequences,
including blindness, and to reduce by one third the
1990 levels of iron deficiency anemia among women
of child-bearing age". Recognizing the possibilities
created by this global movement, a historic con
ference "Ending Hidden Hunger: a Policy Conference
on Micronutrient Malnutrition" was convened by the
World Health Organization and the United Nations
Children Fund (UNICEF) in Montreal in October of
1991. The meeting was supported by the international
development agencies of the United States and
Canada, the World Bank, UNICEF, the United Na
tions Development Program (UNDP), the Food and
Agriculture Organization of the United Nations
(FAO) and WHO. In attendance were three hundred
ministers, policy-leaders and scientists from 55 coun
tries. There were representatives from more than 50
1476S
intergovernment, bilateral and nongovernment
ganizations actively interested in collaborating
overcome micronutrient malnutrition. As an
outcome of the conference, governments have begun
to include the elimination of micronutrient
nutrition as key elements of their plans for national
development (3).
In individual countries, multi-sectoral public
health programs are required on a scale commen
surate with the size and extent of the national
micronutrient malnutrition problem. Since 1991 the
Program Against Micronutrient Malnutrition
(PAMM) supported by UNICEF and the International
Development Agency of the United States of America
(USAID) commenced international training and tech
nical support programs. The strategic focus of PAMM
is to assist national governments to develop and
sustain the technical and management systems that
are required for such programs.
President Suharto of Indonesia included the elimi
nation of iodine deficiency disorders in his election
platform. The 1992 iodine deficiency disorders
control budget is three times that of the total 1991
nutrition budget. President Ramos in the Philippines
has included the control of micronutrient
nutrition in the program for the first 100 days of
office. The Health Ministers in the South Asia Region
Countries (SARC) have declared they wish to achieve
elimination by 1995. Similar high level political com
mitments are being made around the world.
High level regional and national advocacy meetings
are being conducted to address the goal of the elimi
nation of iodine deficiency disorders by the year 2000
such as the "Ending Hidden Hunger" Meeting in the
Philippines, June 9-10, 1993, where President Ramos
addressed his cabinet, private industry and governors
of provinces and the international community
ensure success of the national program. The "Na
tional Advocacy Meeting to eliminate Iodine Defi
ciency Disorders by 2000" in the Great Hall of the
People, Beijing, China, September 21-24, 1993, spon
sored by the state council launched a new national
initiative to eliminate iodine deficiency disorders as a
public health problem in China by the year 2000. If
successful, this will reduce by 30% the world's popu
lation at risk for iodine deficiency disorders. This
meeting also heralded a new level of national cooper
ation. It included, the highest level of government
(premier, vice-premier, state council, seventeen
ministers). A new multi-sectorial program of ac
tivities (health,.industry, agriculture, education, com
munication and finance) was launched. This included
the commitment of twenty provincial governors.
There was cooperation and coordination of support
efforts from the national UN system representatives
(UNDP, UNICEF, WHO, FAO and the World Bank)
and representatives of some of the bilateral donors
(Australia and Canada). The national nongovernment
MABERLY
or organizations (Disabled Association of China, China
to Medical Association, women and children groups) and
international nongovernment organizations (ICCIDD
and PAMM) are also committed to support the new
mal national program.
Recently, other governments are agreeing to meet
the challenge of elimination of iodine deficiency dis
orders. At the 1992 International Conference on
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Nutrition in Rome, governments again confirmed
their commitment to summit goals, this time
specifying particular policies and plans for meeting
these goals. Fortification, supplementation, dietary
diversification, and other public health measures are
feasible methods of preventing micronutrient mal
nutrition. Newly emerging laboratory and infor
mation technologies are simpler, more accurate, more
acceptable and less costly than previous technologies,
so countries will be able to readily determine where
interventions are needed, and to monitor program
activities (19).
United Nations agencies including UNICEF and
WHO have set a number of mid-decade goals towards
achieving the goals of the World Summit for
Children. Universal access by the entire population to
mal iodized salt in all countries with a serious iodine
deficiency disorders problem is perhaps the most tan
gible of these goals. This means that much attention
is being placed upon upgrading the salt system in
many countries, with new processing, packaging,
transport, storage and marketing systems.
INTERVENTIONS
Salt (in many countries), tea (in Tibet), water sup
plies (in certain parts of Asia and Africa), fish paste (in
to Thailand) and bread (in Australia) are examples of
foods that have been fortified to furnish iodine to
iodine-deficient populations. Iodized salt may be the
ideal way to deliver iodine to populations. It is
universally consumed and in a consistent amount
throughout the year. Because it is purchased, the cost
of sustaining the intervention can be passed on to
consumers. Iodine in salt can be delivered in a physio
logic dose with no side effects or toxicity and is very
cost effective at 2-4 cents per person per year. There
are numerous issues that affect the efficacy of salt
iodization programs. These include poor or poorly
enforceable legislation for fortification, poor quality
of salt, poor packaging, storage and transport proce
dures for iodine retention at households, multiple
small scale salt producers, inadequate or incorrect
labeling and market factors that inflate the cost of
iodized salt.
Iodine may also be delivered in oil either by in
jection or oral capsules. This has the advantage that a
single dose will supply adequate iodine for 1-3 years;
however, the dose is rather large and its safety in
 SYMPOSIUM: CLINICAL NUTRITION
certain populations, e.g., pregnant women, is not
clear. The cost is approximately U.S. $0.08 per year
per person for oral iodized oil and U.S. $0.50 for
iodized oil injection. This strategy may be more ap
propriate for remote regions which are problematic
from the point of view of salt distribution and
transport on a regular basis. In addition, no national
legislation is required (4).
COMMUNICATIONS AND SOCIAL
MARKETING
Programs directed towards the sustained elimi
nation of iodine deficiency disorders need to be
broadly based so that interventions become accepted
community practices. Hence program tactics need to
be synchronous with this objective and dependent
upon the empowerment of people to agree with and
arrange for an adequate intake of iodine. To achieve
and sustain this status requires a network of people
within various organizations who consider it worth
while to commit to this endeavor (20, 21).
SURVEILLANCE AND MONITORING
Accurate assessments of the extent of
micronutrient malnutrition throughout the world are
not currently available and are subject to change on a
yearly basis. There are several reasons for this. Many
of the most seriously affected countries have only
recently recognized the importance of iodine defi
ciency disorders. Most of the affected countries do not
have up-to-date epidemiological data on iodine defi
ciency disorders but have instead information about
outdated small selective studies in certain areas. The
nature of iodine deficiency disorders is such that it is
not overtly evident in the affected populations. Hence
the term "hidden hunger" has been coined by
UNICEF and WHO. Frequently used clinical criteria
of cretinism in the population and goiter in school
children are highly subjective. When tested against
thyroid ultrasound or biochemical factors, these
clinical methods have frequently been shown to
greatly underestimate the extent and severity of the
problem. Countries frequently have not invested the
resources to attain the technical capacity to un
dertake the surveys, process the samples and the data,
and interpret and act upon the results. Finally, more
data needs to be gathered and compared from a
number of affected countries with various levels of
severity of iodine deficiency disorders so that clear
public health criteria for severity can be agreed on to
enable effective surveillance in and among countries.
This surveillance data needs to be presented as
prevalence estimates for advocacy, policy and re
source allocation. Because resources for surveillance
IN DEVELOPING COUNTRIES 1477S
and monitoring are limited, other approaches need to
be taken. These include spot sampling or "lot quality
assurance" in suspected affected regions to determine
whether or not a program is in place. Issues of
representativeness of the sample in these circum
stances are much less important. Assessments need to
be made upon the efficacy of the program as well as
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the status of the population (4, 19).
TRAINING AND TECHNICAL SUPPORT
The Program Against Micronutrient Malnutrition
in Atlanta has provided in-depth multi-sectorial on
going training and technical support to 100 par
ticipants involved in national iodine deficiency dis
orders control from 20 countries during the last two
years. Training is then being replicated in country to
build strong provincial units. These units focus in
turn on the county or community. The establishment
of an ongoing technical communication network and
expert in country consultation are also an essential
part of this process. Other training and support pro
grams are being implemented from a number of other
institutions. Cooperation among these training and
support centers would facilitate the elimination of
iodine deficiency disorders.
RESEARCH AND DEVELOPMENT
Newly developed laboratory and information tech
nologies are simpler, more accurate, more acceptable
and less costly than those previously available so that
countries now can readily determine the magnitude
and distribution of the problem and evaluate potential
solutions. Further innovations in advocacy, commu
nications and social marketing, interventions and
evaluation would enhance the potential for successful
elimination.
LITERATURE CITED
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in Human and Animal Nutrition (Mertz, C., ed.), voi 2, pp.
139-208. Academic Press, New York, NY.
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3. Ramalingaswami, V. (1992) Challenges and opportunities—
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