Volume 14 Number 3 August 1998
IN THIS ISSUE
PROGRESS AGAINST IDD IN MYANMAR
IODINE IN PREGNANCY
SUSTAINABILITY OF IDD ELIMINATION IN JIANGSU PROVINCE,
CHINA
SUSTAINING THE VIRTUAL ELIMINATION OF IODINE
DEFICIENCY DISORDERS IN NIGERIA AND THE WEST
AFRICAN SUBREGION
REPEATED LOW ORAL DOSES OF LOCALLY PREPARED
IODIZED OIL FOR IODINE DEFICIENCY IN THAILAND
ABSTRACTS
IODINE INTAKE AND THE PATTERN OF THYROID
DISORDERS: A COMPARATIVE EPIDEMIOLOGICAL
STUDY OF THYROID ABNORMALITIES IN THE ELDERLY
IN ICELAND AND IN JUTLAND, DENMARK by R. Laurberg,
et al.
THE INCIDENCE OF HYPERTHYROIDISM IN AUSTRIA
FROM 1987 TO 1995 BEFORE AND AFTER AN INCREASE
IN SALT IODIZATION IN 1990, by A. Mostbeck, et al.
CONSEQUENCES OF IODINE DEFICIENCY IN CATTLE IN
SOME REGIONS OF THE CZECH REPUBLIC, by J. Kursa,
et al.
IN BRIEF
IODINE IN PREGNANCY BOOK
ANDEAN SUBREGIONAL MICRONUTRIENT PROGRAM
IODIZED WATER IN MEXICO
THYROMOBIL IN LATIN AMERICA
RUSSIA AND CENTRAL ASIA
WORKSHOP ON IDD CONTROL PROGRAMS IN RUSSIA
BELGIUM
NATIONAL IDD PROGRAM ASSESSMENT TOOL (ISPAT)
DELANGE HONORED
IODINE DEFICIENCY IN BREAST CANCER DISCUSSED IN
JAPAN
PROGRESS AGAINST IDD IN MYANMAR
Myanmar has a unique opportunity to achieve universal salt
iodization by the year 2000, according to a report entitled "Universal
Salt Iodization in Myanmar: From Sea Water to IDD Elimination,"
published by UNICEF in June 1998 and kindly forwarded to the IDD
Newsletter by Dr. Juan Aguilar Leon, UNICEF Representative in
Myanmar. The report traces the history of efforts to control IDD in
Myanmar during the past 30 years, supplementing occasional
reviews in the IDD Newsletter in the past decade.
Surveys in the 1960's reported prevalence rates for endemic
goiter of 50-90% with frequent evidence of cretinism, deaf-mutism,
and mental retardation, particularly in the states of Chin, Kachin, and
Shan. In addition to these mountainous areas, iodine deficiency also
was found in central low-lying areas. The government established a
National Goiter Control Committee in 1968, chaired by the Deputy
Minister of Health, with representation from the Ministries of Health
and of Trade and Mines. Iodized salt began to be distributed by the
Committee in pilot townships in Chin, Sagaing, and Magwe. The
Ministry structure at that time consisted of a Government Trade
Cooperation, the mandated buyer of all private salt production, and
salt was distributed through the Cooperation's shops. UNICEF
donated six salt iodization machines, iodine, and laboratory
equipment. The iodized salt was produced and distributed by the
Trade Cooperation, with staffing by the Ministry of Health. The cost
of iodization was subsidized by the government. The iodization level
was set at 80 ppm, estimated to supply 350-500 mcg iodine/person
daily.
Initial progress was encouraging. By 1972 goiter rates in five
townships in Chin were 25%, compared to 92% before the program
began. A change in government policy in 1976 shifted production
and distribution to the private sector. After that, production of iodized
salt steadily decreased, stopping completely in 1980. By 1982, the
goiter prevalence had returned to 76%. Later a National IDD Control
Committee was set up to plan another iodized salt distribution
program, but action was delayed until 1989, when it covered 25
townships. Meanwhile, an iodized oil program began, first starting in
1982 with Lipiodol by injection in nine townships with high goiter
prevalence. The primary targets were women of childbearing age
and children up to age 14. The coverage was estimated at 71% and
was accompanied by a decrease of 25% in goiter prevalence. Later,
between 1987 and 1990, iodized oil was administered orally in 13
townships, 200 mg of iodine for those under one year old, 400 mg
for those above, with 91% coverage. In 1991, an IDD Control
Program was defined by the National Health Plan with iodized salt
for the long term and oral iodized oil as a short-term measure.
The private sector produces most of the country's salt. The
Ministry of Mines developed training programs for managers of major
salt refineries with special attention to iodization techniques and
quality control. UNICEF provided iodine and laboratory equipment.
The Ministry of Health trained local health staff to monitor availability
and iodine content of iodized salt. Advocacy, aimed at local
authorities, the health sector, and the general population, was an
important part of the program.
During the dry season (October to May), salt is evaporated from
sea water along the coast, at 11 government and more than 1070
private salt farms. Annual production can reach 250,000-300,000
metric tons, each year, enough to meet the country's requirement.
About 51% of the salt is for household use, and another 24% for
human consumption in the form of preservation and beverages. The
coordinating agency within the salt industry is the Myanma Salt and
Marine Chemical Enterprise (MSMCE). It licenses private salt farms,
monitors quality and quantity of production, conducts training, and
coordinates KIO3 supplies. It works through five zonal offices,
through which it participates as Secretary of the local IDD Committee
in the respective state or division. Currently, there are 109 private
refineries where salt is iodized, with production capacity ranging from
2 to 200 metric tons per day.
Refining involves grinding, washing, and drying in basket
centrifuges. The salt is iodized either by submerging the refined salt
in iodized brine and recentrifuging, by adding KIO3 in the wash brine
that circulates in the refining system, or by spraying KIO3 and brine
over salt during centrifugation. The latter method is currently
favored. It requires only a plastic container as KIO3 solution
reservoir, spraying equipment (an ordinary shower head is frequently
used), and plastic tubing to connect the two. Recommended
levels for iodization in Myanmar are 40-60 ppm at production, and 25
ppm at the consumer level, based on a daily salt consumption of 10
grams and iodine ration of 150 mcg/day. The iodized salt is packed
in bulk or small packs in HDPE bags, and transported to distributing
points.
The manufacturers are expected to carry out regular quality
control monitoring of their iodized salt. In addition, the MSMCE,
carries out periodic checks of salt producers, by examining records,
checking equipment and analyzing random samples in zonal
laboratories. The MSMCE has also established three private salt
producers association. Their form and activity differ, but all have the
objective of producing iodized salt.
Several years elapsed in the 1990's before iodized salt became
available. Producers balked because of the heavy income tax on
iodized salt, the dual market with noniodized salt, a perceived lack of
demand, and competition from the cheap subsidized iodized salt
produced by the government.
In 1996 the country adopted universal salt iodization, and the
managing director of the MSMCE ordered all producers to sell only
iodized salt. Failure to comply carried the risk of factory closure.
Similar orders were made by local authorities. The chairman of the
National Health Committee in 1997 demanded that all salt for human
and animal consumption should be iodized. Yearly production of
iodized salt rose from 2,103 MT in 1992 to 111,893 in 1998. A
target of 230,000 MT by the year 2000 was set, to include all salt for
human and animal consumption. UNICEF has supported the effort
through training, advocacy, and provision of KIO3 and laboratory
equipment.
Since 1997, increasing attention has been given to
sustainability. Strategies include resolving fund for purchase of KIO3,
strengthening of quality control at production sites, and consumer
education. Primary responsibility rests with the Ministry of Mines and
the MSMCE, with the National Nutrition Center of the Ministry of
Health designated for impact evaluation. A revolving fund for
obtaining additional supplies is being set up, with funds with KIO3
sales. UNICEF and UNDP have assisted. Quality control is carried
out at the production level by the producers themselves, analyzing
the iodized salt by titration. MSMCE officers visit salt factories,
check records, and offer training at least twice a month. They take
samples for analysis at the central labs.
At the consumer level, township IDD committees work with the
Department of Development Affairs and city development committees
to assess the availability and quality of iodized salt in the market.
Household consumption of iodized salt is monitored through the
schools, and will be extended to 30 sentinel townships, using test
kits. A national consumer education campaign is being planned,
through different media approaches. Impact monitoring is
programmed to include yearly urinary iodine excretion surveys in
schoolchildren, carried out by the National Nutrition Center, as well
as continuation of regular goiter surveys. Surveys assessing goiter
and urinary iodine excretion are scheduled for 1998, 1999, and 2000.
Conclusions
Approximately 30 million people live in iodine-deficient areas
and risk its consequences, particularly in the states of Chin, Kachin,
and Shan. A government program with iodized salt 30 years ago
later failed when government policy changed by shifting production
and distribution to the private sector. An IDD control program was
developed in 1991, leading to the adoption of universal salt iodization
in 1996. Yearly production of iodized salt has risen dramatically and
is expected to reach 230,000 metric tons in the year 2000, sufficient
for all human and animal needs. Monitoring of iodine levels in salt
and impact monitoring by urinary iodines and regular goiter surveys
are being carried out.
IODINE IN PREGNANCY
ICCIDD has published a book with the above title (Oxford
University Press, Delhi, 1998). Its production was prompted by the
increasing recognition that the most damaging consequences of
iodine deficiency occur in the early stages of human development.
Pregnancy makes iodine nutrition more complex because both the
mother and the fetus are affected, and proper nutrition for the fetus
must come via the mother. The most important concern for the fetus
is inadequate iodine, but it is also sensitive to excess iodine as well.
Careful attention to delivering the optimal amount to the fetus
through the mother should be the major objective of iodization
programs. The book reviews iodine requirements during brain
development, fetal and maternal thyroid physiology, field studies on
the effects of iodized oil during pregnancy, and related topics
including treatment in nuclear radiation exposure, assessment and
monitoring techniques, and economic consequences. The present
article summarize the individual chapters. Some of their topics have
been discussed extensively in recent Newsletters and elsewhere,
and are described only briefly here.
Thyroid hormone and iodine requirements in man during
brain development, by D. A. Fisher and F. M. Delange - This
chapter provides a detailed review of the requirements for iodine and
thyroid hormone during the period from conception to the third
postnatal year. The fetal thyroid is first capable of function around
12 weeks of gestation, and becomes progressively active thereafter.
The placenta has limited permeability to thyroid hormones,
throughout gestation. Distribution of thyroid hormone action may be
selective for individual tissues, with response developing in different
tissues at different times; an approximate order is placenta,
pancreas, pituitary, brain, bone, heart, lung, and liver. Only 10-15%
of T4 in the fetus is metabolized to active T3, because of a relative
deficiency of deiodination, and active sulfation of thyroid hormones.
During the 20th to 40th weeks of gestation, serum TSH and
free T4 steadily increase, reaching a plateau at about 35 weeks.
Premature infants have immature thyroid function, but treatment in
the period 25-30 weeks of gestation did not improve development in
several experimental studies. The authors discuss the optimal
treatment dose for thyroid hormone in congenital hypothyroid infants,
noting that adequate early treatment can prevent or minimize brain
damage. After reviewing extensive observational data, they
recommend an initial dose of 11 mcg/kg/day, then 8-10 mcg/kg/day
for one to six months, 6-8 mcg/kg/day for six to 12 months and 5-6
mcg/kg/day from the period one to five years. Previous
recommendations have been 40 mcg iodine/day in infants aged 0-6
months. Existing data on breast milk iodine content show wide
variations. An average breast milk consumption of 700 ml/day gives
an iodine intake of about 56 mcg in Europe and 112 in the United
States. A net positive iodine intake is important in the young infant
to meet the increasing need for iodine stores in the thyroid, and
requires at least 15 mcg/kg/day in the full term infant and 30
mcg/kg/day in the preterm infant. This corresponds to 90 mcg/day
from birth onward. To reach this level, the iodine content of formula
milk should be 100 mcg/L for full term and 200 mcg/L for preterm
infants. Based on these considerations, WHO and ICCIDD now
recommend an iodine intake of 90 mcg/day from birth through the
first year, 90 mcg/day for one to six years, 120 mcg/day from seven
to 12 years, 150 mcg/day in adults, and 200 mcg/day during
pregnancy and lactation. Newborns may also be exposed to iodine
excess, for example, from iodine-containing skin antiseptics applied
to the mother or infant. This may result in transient hypothyroidism,
and should be considered if such exposure has occurred.
Thyroid size and thyroid function during pregnancy, by A.
Berghout and W. M. Wiersinga - The authors give a
comprehensive review of some 15 publications that assess thyroid
size during pregnancy, and relate it to iodine intake in the test
community. Studies since 1987 rely on ultrasound, and the authors
emphasize the relative crudeness of assessments by palpation in
studies before that time. Six of the earlier studies carried out in
areas of iodine sufficiency failed to find thyroid enlargement during
pregnancy. An increase was typical in studies from iodine deficient
countries. In an example from Belgium, thyroid volume increased
from 12.1 ml to 13.9 during pregnancy and to 15.0 shortly after
delivery. Another report from Belgium described an increase of
thyroid volume by 30% from first trimester to delivery. Similar
enlargement was reported in Italy and Ireland. In contrast, in the
iodine-sufficient Netherlands (mean iodine concentration 147 mcg/24
hours), thyroid volumes were 10.3 ml before pregnancy and
remained essentially the same during all three trimesters. Studies
from some of the iodine-deficient areas showed that treatment with
iodine during pregnancy could eliminate or reduce the enlargement
found in untreated controls. Fewer data exist on thyroid function
tests, but at least some suggest a decrease in T4 and an increase in
TSH in association with iodine deficiency. The authors found in an
iodine-sufficient area a decrease in free T4 by about 30% in the
second and third trimester. In the first trimester, free T4 increases,
probably in response to stimulation by HCG which peaks in the first
trimester. TSH concentrations generally did not change in iodine-
sufficient areas. Overall, the thyroid does not increase its size during
pregnancy in the presence of adequate iodine, but does enlarge with
iodine deficiency.
Iodine supplementation of a cross-section of iodine-
deficient pregnant women: does the human fetal brain undergo
metamorphosis? by G. R. DeLong, C. Xue-Yi, J. Xin Min, D. Zhi-
Hong, M. A. Rakeman, Z. Ming Li, K. O'Donnel, Ma Tai, K.
Amette, and N. DeLong - The authors' objective was to clarify the
point during fetal and postnatal development at which the effects of
iodine deficiency are still reversible. The study was carried out in
Tusala in Xinjiang in western China, an area where 2% of the
population were cretins, 54% had visible goiter, and the mean urinary
iodine excretion was less than 25 mcg/L. The authors treated 689
children, from newborn to three years of age, and 295 women at
different stages of pregnancy, with oral iodized oil (50 mg iodine 0-12
months, 200 mg for older children, and 400 mg for adults). Indices
were neurological examination, head circumference (which correlates
with brain weight in the first postnatal year), and developmental
achievement. Control subjects were children first seen before
receiving treatment. Treatment with iodine at any time after the
second trimester had no effect on neurological outcome when
assessed at age one to two years. Treatment during the first or
second trimesters clearly improved neurological outcome.
Interpretation was complicated because the mothers treated in the
first trimester mistakenly received only a small dose of iodine (100
mcg for each of four days). The children treated during the second
trimester had a significantly larger head circumference, lower
prevalence of microcephaly, and a development score of 90,
compared with those treated in the third trimester (80), 0-3 months
(79), 3-12 months (80), and untreated (75) on assessment at two
years. Results show that after the beginning of the third trimester
the abnormalities in head growth and neurological development are
irreversible, although some improvement occurred in those treated
during the third trimester.
The authors conclude that a T4-dependent event occurs at a
fairly narrow interval at the beginning of the third trimester and this is
important for subsequent brain growth. They refer to this as a
metamorphosis in that provision of adequate iodine is essential to
provide adequate thyroid hormone. The authors point to the parallel
of premature infants born at less than 27 weeks of gestation whose
subsequent mental development score was improved by
administration of thyroxine compared with those given placebo.
Relationship of maternal iodine status to neonatal TSH
levels, by L. Shi, Z. Shi, and S. C. Boyages - The authors review
their experience in Guizhou Province in China with neonatal TSH
monitoring as an indicator of iodine deficiency. The area had a
goiter prevalence of 60%, a cretinism rate of 5.2%, and a mean
urinary iodine level of 27 mcg/L. They examined 95 pregnant
women and their neonates. Capillary or cord blood samples were
collected on filter paper and analyzed for TSH by IRMA. They found
that 61% had blood spot TSH levels between 0-5 mIU/L, 11% had
more than 10, and none were greater than 20. In iodine-sufficient
Australia 95% of newborns have blood spot TSH values less than 5.
The maternal TSH levels at the end of pregnancy were all normal.
While the median urinary iodine level in the mothers was sufficient
(102 mcg/L), the range (22-238 mcg/L) was wide. A strong inverse
correlation existed between neonatal blood spot TSH and maternal
urinary iodine levels. The authors conclude that neonatal TSH
monitoring is a sensitive indicator of the iodine deficiency in a
community, and provides a better overall picture than other biological
measures. They suggest two important phases of brain vulnerability
to iodine deficiency, the first between 12 and 18 weeks of fetal life,
and the second beginning in mid-pregnancy and maximal around
birth and the following six months.
Studies of the effect of iodized oil on fetal development in
severely iodine deficient sheep, by B. S. Hetzel - This paper
summarizes experimental work on the effects of iodine deficiency in
a sheep model and its implications for effects of iodine on human
brain development. Dietary iodine deficiency was established in 30
ewes, and 10 of them were given IM iodized oil as a control. Ewes
were mated with iodine sufficient rams and at 100 days, 8 of the
iodine-deficient ewes received an IM dose of iodized oil, 400 mg. All
ewes were delivered at 140 days (10 days before normal parturition).
Iodized oil administration at 100 days of gestation restored the fetal
wool coat that was absent in the iodine-deficient fetus, and also
changed abnormalities in the cranium, foot joints and bone
maturation, although body weight remained significantly below
control values. Iodized oil reduced fetal thyroid weight, increased
iodine content, and returned thyroid histology towards normal.
Maternal and fetal TSH values were reduced compared to those in
the iodine-deficient controls. Iodized oil increased fetal brain weight
but not to the size of iodine-sufficient controls. Brain cholesterol
followed a similar pattern. Iodine deficiency was associated
histologically with changes in the areas of cerebellar layers and
these were corrected by iodine administration. Iodine-deficient brains
showed deficient synaptic density, which improved considerably with
iodine supplementation but did not reach the status of the iodine-
sufficient controls. The author concludes, based on the sheep
model, that administration of iodized oil during pregnancy had
marked benefit on brain development and did not have any adverse
effects. Extrapolation from the sheep model suggests that iodized oil
administered during pregnancy has beneficial effects.
The pharmacology and toxicity of iodinated oil, by J. B.
Stanbury - Iodinated vegetable oil was originally developed as a
radiocontrast medium. It was first applied for iodine prophylaxis in
Papua New Guinea in 1959, and subsequently in Ecuador, Zaire,
Peru, Nepal, China, and other countries. The most common
preparation available globally is Lipiodol, containing 480 mg
iodine/ml, manufactured by Laboratoire Guerbet in France. A related
oral preparation, Oriodol, also produced by Guerbet, contains 540
mg iodine/ml. Capsules of 200 or 400 mg iodine are available for
oral use. Linoleic acid is the principal fatty acid of Lipiodol. Work in
rats has shown some difference in retention and metabolism
depending on the specific fatty acid iodinated. Following
intramuscular administration, iodized oil is slowly released and
distributed by regional lymphatics to fat depots, and then slowly
released into the circulation and picked up by the thyroid. Following
oral administration, iodized oil is degraded in the intestine and
absorbed largely as iodide, but some is stored in fat. A number of
clinical studies suggest that a single oral administration of 480 mg
iodized oil provides coverage for about one year and administration
intramuscularly for two to three years. Considerable variation exists
among studies, probably related to the preparation and the group
being studied, particularly their nutritional status. Experiments in
animals show that the iodine from iodized oil is concentrated in the
mammary gland and appears in milk. Increase in breast milk iodine
has also been shown in humans after both intramuscular and oral
administration of iodized oil. Administration of iodized oil to pregnant
experimental animals has shown progressive accumulation in the
fetal thyroid. Iodized oil has been remarkably free of toxic effects;
transient salivary gland inflammation is occasionally noted. Some
cases of iodine-induced hyperthyroidism have also occurred. While
the issue of fetal damage from iodized oil administration in
pregnancy has been occasionally raised, careful review of the
literature fails to substantiate the occurrence of neonatal
hypothyroidism in iodine-deficient humans following administration of
iodized oil to mothers. To the contrary, it is well established that
iodized oil administration, particularly early in pregnancy, has clearly
beneficial effects on fetal development.
Acute effects of oral iodized oil in iodine deficient goitrous
subjects, by A. Boudiba, R. Maoui, and M. Benmiloud - An
elevated serum thyroglobulin concentration is a consistent although
nonspecific finding in endemic goiter and other conditions with
thyroid hyperplasia. An increase in serum thyroglobulin has been
reported after acute administration of iodine. The authors gave 0.5
ml iodized oil (240 mg iodine) orally a week before surgery to each
of seven goitrous subjects scheduled for thyroidectomy for
multinodular goiter. During the first three days serum concentrations
of T4, T3, free T4 and free T3 increased, and serum TSH decreased.
Urinary iodine levels reached a peak on the first day, at 26,000
mcg/g creatinine, decreasing to 2,309 by the eighth day. The
maximum serum thyroglobulin was on day 2. Despite the changes,
T4 and TSH remained within the normal range. The authors
conclude that the increased serum thyroglobulin is probably due to
increased release from a direct effect of iodine on the nodular
thyroid.
Iodine nutrition during pregnancy: iodinated oil and fetus:
results from Papua New Guinea, by P. O. D. Pharaoh and K. J.
Connoly - A control trial took place beginning in September 1966,
when women were given intramuscularly either 4 ml of iodinated
poppyseed oil (475 mg iodine/ml) or a saline placebo, and the
outcome of subsequent pregnancies assessed. Group 1 received
the iodized oil during pregnancy and group 2 received it prior to
conception. The authors had previously reported no difference in the
prevalence of cretinism between placebo and those receiving iodized
oil after conception. In the current study, they address the issue of
whether any adverse effects occurred following iodized oil. Follow-
up took place during the first few years after birth and also during the
following 15 years. Height was greater in the group whose mothers
had received iodine. Measurement of hearing ability and motor
function showed no significant differences between groups 1 and 2.
Also, cognitive function as measured by the specific design
construction test failed to show a difference. The authors note the
limitations of this retrospective analysis, and the difficulty of applying
conventional statistical approaches. However, in most of the
comparisons the children whose mothers had received iodized oil
performed better than the controls. The authors conclude that the
administration of iodized oil during pregnancy certainly had no
adverse effects on subsequent fetal development. It should be noted
also that the dose of iodized oil was quite high, much greater than
currently used for prophylaxis.
Acute effect of iodized oil on thyroid function in young
adults, by G. Gerasimov, N. Sviridenko, and F. Delange - This
study also addressed the question of whether iodized oil
administration is likely to have adverse effects on the fetus, by
assessing the acute effects on the thyroid axis of a single large dose
of 400 mg of iodine (two capsules of Lipiodol). The subjects were
five young males and five nonpregnant females from an area with
mild iodine deficiency in Russia (median urinary iodine 69-75 mcg/L).
The median urinary iodine rose from 102 mcg/L before administration
to a maximum of 2380 on the third day, and was 290 at day 30. The
initial median serum TSH was 1.49 mU/ml, the free T4 15.1 pmol/L,
and the thyroglobulin 15.9 ng/ml. There were no significant changes
in any of these parameters during the 30 days following
administration. Initial thyroid volume was 17.6 ml for males and 14.5
for females, and these did not change during the 30 days following
iodized oil administration. The authors conclude that 400 mg of
iodine in iodized oil showed no significant inhibitory effects on the
thyroid axis in these young subjects. This indicated that
administration of iodized oil under these circumstances, which are
similar to those in an iodized oil program that includes pregnant
women, should have no adverse effects on the maternal thyroid
status and should, therefore, deliver adequate amounts of maternal
thyroid hormone to the developing fetus.
Iodine nutrition: consideration of prophylaxis and
treatment with regard to nuclear radiation exposure, by P. B.
Zanzonico and D. V. Becker - Nuclear reactor accidents, such as
Chernobyl, may release large amounts of radioactive iodine,
principally 131I. The emergency response to these accidents is
widespread administration of KI, to block thyroidal uptake of the
radioactive iodine and prevent its effects on the thyroid. The
potentially damaging effects of the radioactive iodine are
substantially higher in iodine deficiency because the deficient thyroid
concentrates iodine, including radioactive iodine, more avidly. The
long-range effect may be a substantial increase in childhood thyroid
cancer. In pregnancy, maternal iodine is rapidly distributed to the
fetus. The fetal thyroid does not accumulate iodine during the first
trimester. During the last half of pregnancy, the fetal thyroid may
accumulate up to a maximum of about 3% of the iodine administered
to the mother. Fetal radioiodine accumulation, when expressed as
absorbed radioactivity per gram thyroid tissue, reaches a maximum
at about 24 weeks of gestation, decreasing thereafter because the
fetal thyroid mass increases more rapidly. The fraction of
radioactivity in the fetal thyroid is about 0.1-0.3% per gram thyroid
tissue at the time of delivery. Dosimetry models indicate that the
fetal thyroid absorbed dose reaches a maximum of nearly 5,000 rads
per mCi 131I at 24 weeks, decreasing to about 2,000 rads per mCi at
term when the mother is euthyroid and iodine sufficient.
The authors review recommendations for use of KI following
nuclear accidents. A single dose of 30 mg KI will provide a 95%
protective effect, although the authors recommend the higher dose of
100 mg iodide (130 mg KI) as a standard adult dose, and 65 mg for
children. From models of iodine distribution, KI administration up to
48 hours before 131I exposure will block thyroidal uptake almost
completely. To be maximally effective, blockade with KI should be
given no earlier than three days before and not later than eight hours
after radioactive iodine exposure. Blockade before exposure is more
effective in the iodine deficient than in the iodine sufficient subject,
but it is less effective after 131I exposure. A compartmental model
can predict the amount of radioactive iodine absorbed by the fetus
with and without KI blocking. In iodine sufficiency, the maternal
thyroid has an absorbed dose of 1,460 rads per mCi 131I without
blocking and 19.9 with blocking, while the fetal thyroid has 4,820
without blocking and 65.6 with blocking. In iodine deficiency, the
respective figures are, for the mother 2,980 and 8.6, and for the
fetus, 1,960 and 45. Also, KI blocking greatly reduces the
extrathyroidal absorbed dose in both mother and fetus.
Following Chernobyl, some 17 million doses of 70 mg KI were
given rapidly with few and apparently mild adverse effects.
Professional and international groups have recommended rapid
administration of KI after nuclear exposure. The authors recommend
that KI should be given to infants, children, and adolescents up to
age 16 after both near and more distant radioactive exposure.
Different recommendations exist for level of exposure that should
trigger intervention, but generally are about 25 rem for adults and
about 5 rem for children. The recommended KI dose is 130 mg for
adults, 50 mg for children, and 12.5 mg for infants. Pregnant women
should specifically be included in such programs of prophylaxis.
Method for assessing and monitoring iodine nutrition, by J.
T. Dunn - Effective assessment and monitoring are essential for
achieving adequate iodine nutrition, especially in the most vulnerable
parts of the population - pregnant women, other women of
childbearing years, and children. This paper reviews the available
techniques. Most have been discussed in previous issues of the
Newsletter. Currently, the single most useful laboratory marker is
urinary iodine concentration. Most ingested iodine is eventually
excreted in the urine. Casual samples taken from 30 or more
individuals and expressed as a concentration are satisfactory for
epidemiologic purposes. Most available techniques depend on the
Sandell-Kolthoff reaction, in which iodide catalyzes the
disappearance of ceric ammonium sulfate's yellow color in the
presence of arsenious acid. A simple method, Method A, requiring
only a heating block and colorimeter, has been adapted by ICCIDD
and others and is widely used in developing countries. Thyroid size
can be evaluated by palpation, or better, by ultrasonography.
Palpation is satisfactory for large thyroids, but is less reliable for
small thyroids or in children. Portable ultrasound instruments can be
carried to the field, require only electricity, and provide precise
quantitation of thyroid size. Urinary iodine concentration assesses
iodine nutrition over the several days before collection, while thyroid
size shows effects over a longer duration - months, or even years.
The serum thyroglobulin is another useful marker and, in general,
parallels thyroid size. It can be measured with blood spots.
Neonatal TSH by blood spot is also a good indicator of community
iodine nutrition. The incidence of transient neonatal hypothyroidism,
as shown by elevated neonatal TSH, is proportional to community
iodine deficiency. Most Western countries use universal neonatal
screening with TSH as a means for detecting congenital
hypothyroidism, which occurs in iodine-sufficient countries in
approximately one of every 4000 births, usually from thyroid aplasia.
It will be years before most developing countries establish programs
for neonatal screening, and until then, this indicator will not be a
practical way for them to assess iodine deficiency. Other standard
tests of thyroid function, including the serum thyroxine, serum
triiodothyronine, and thyroid radioiodine uptake, are less useful for
detecting iodine deficiency, because their ranges of normal are wide
and they may be more expensive and cumbersome than urinary
iodine. Dietary surveys, particularly iodized salt use, also provide
useful information for monitoring. Such data allow an estimate of
probable iodine intake at the community level, and complement, but
do not replace, information from direct biological monitoring.
Pregnancy, high risk population and iodine
supplementation in India - An economic analysis, by C. S.
Pandav - Sikkim, with a population of 400,000, has severe iodine
deficiency, with a goiter prevalence of 55%. Its government
considered establishing a salt iodization program, an iodized oil
injection program, or a combination. This paper examines the
economic consequences of these choices. It compares no
preventive program, an iodized salt program, and an iodized oil
program, with reference to the year 1991. The direct costs involved
in an iodized salt program include monitoring activities and
communication strategy from the health sector, and salt iodization
equipment, supplies, and personnel from the salt sector. Direct costs
in the iodized oil program are all in the health sector, and include the
iodized oil capsules, syringes, personnel, transportation, and a
communications strategy, professional time, and travel costs. Details
of each program are highly specific to individual countries. For
Sikkim, salt is imported from western Indian states, covers the entire
population, could be handled by one iodization plant, and would
require a communications strategy and salt monitoring laboratories.
An iodized oil program would aim at children and women of
childbearing age, injection of 1 ml (480 mg iodine), and would be
handled by the primary health care system. It also would require a
communications component. The analysis considered the
consequences of IDD related to physical function, and the changes
in resource use. The author carefully details the many assumptions
inherent in such an analysis including the incidence and the cost of
management of mental impairment from iodine deficiency, the
utilization of services in an ongoing program, medical care, and
productivity gained both from improved work performance and from
decreased demand for corrective health services. Cost estimates
are given in Indian rupees. The total capital cost for a salt iodization
plant is 2.3 million rupees, a total annual operating cost is about
700,000 rupees. Thus, the total cost for salt iodization for a year is
slightly over one million rupees. Additional costs are for monitoring
laboratories (283,000) and communications (296,000), bringing the
total cost per year for the program to 1,612,000. For the estimated
population of Sikkim, the cost would be 4 rupees per person per
year. The cost for the iodized oil program is estimated at 5,238,000
rupees, as a one-time administration, projected for five year's
coverage, giving an annual cost of 1,256,000 or 5.2 rupees per
person protected per year. Based on these and many other
assumptions, the analysis provided several cost estimates. It
estimated a benefit:cost ratio of 1.38 for the iodized salt and 1.71 for
iodized oil. The author stresses the limitation in the items included,
particularly benefits and the assumptions involved. Under these
circumstances, iodized oil program appears to be more cost effective
than iodized salt, but this conclusion is limited to the particular
assumptions involved and the specific example of Sikkim. This
general approach to cost benefit analysis can help identify the most
important elements and design the most cost effective strategies for
eliminating iodine deficiency.
World Health Organization statement on safe use of iodized
oil to prevent iodine deficiency in pregnant women - The
considerations and recommendations in this statement resulted from
a 1994 WHO consultation, chaired by and with prominent
representation from ICCIDD. The IDD Newsletter (11(2):25, 1995)
summarized its deliberations. The conclusion stated "based on the
available scientific and programmatic evidence, the proposed iodized
oil prevention schedule in this statement will lead to no detectable
adverse effects on human health. The potential benefits to be
derived greatly outweigh the potential risks in areas of moderate and
severe IDD prevalence where iodized oil is not available and is
unlikely to be made available in the short term, i.e., within one to two
years." Recommended doses for pregnant women were 480 mg
iodine (1 ml) of Lipiodol intramuscularly , 300-480 mg orally.
Administration of iodized oil during pregnancy: a summary
of the published evidence, by F. M. Delange - This article is a
background scientific paper prepared by Dr. Delange in 1994 for the
WHO consultation, summarized briefly in the IDD Newsletter
(11(2):25, 1995). It presents a comprehensive review of available
studies of iodized oil administration during pregnancy. The author
concludes that "despite the massive doses of iodine administered, no
iodine-induced thyroid function abnormalities have ever been
conclusively demonstrated at the time of delivery or in the short or
long term follow-up of pregnant women and their offspring. The
potential benefits derived from using iodized oil immediately before or
during pregnancy greatly outweigh the potential risk in areas of
moderate and severe prevalence of iodine deficiency disorders,
where iodized salt is not available or unlikely to be available within
one to two years."
Also, ICCIDD published a short statement (IDD Newsletter
11(2):25, 1995) recommending that pregnant women should be
included in programs where iodized oil administration is appropriate.
SUSTAINABILITY OF IDD ELIMINATION IN JIANGSU PROVINCE,
CHINA by Zhao Jinkou, Department of Endemic Disease Control,
Station for Health and Epidemic Prevention, Nanjing.
Jiangsu is a coastal province of 70 million people, north of
Shanghai. Following the Chinese National Advocacy Meeting to
Eliminate IDD by the year 2000 in 1993, and a comparable
commitment made by the Jiangsu provincial governor in 1994, great
progress has been made to implement a comprehensive control
program, based on universal salt iodization, oral iodized oil to
vulnerable targets, and health education.
In 1994, the Chinese government issued the "Regulation on Edible Salt Iodization as a
Means to Eliminate IDD," which governs salt production, iodization,
marketing, quality assurance, and IDD surveillance. The Jiangsu
provincial governor endorsed a comparable ordinance based on the
national regulation, stipulating the responsibility of the relevant social
sectors concerning IDD elimination in the province. Since then, a
substantial proportion of the human and financial resources required
to achieve the goal has been mobilized. The province established a
system of professional organization and team. The responsible vice
governor appointed the chief of the office of endemic diseases
control (EDC) to coordinate the program. Funding of about 150
million yuan (US $200,000) was provided in the provincial annual
financial budget. Many sectors were involved in disseminating
information on the consequences of IDD and the importance of its
control.
These efforts lead to steady improvements in the quality and
coverage of iodized salt. Currently, 90% of the population receives
adequate iodine by this means. Extra supplements of iodized oil are
given to women of childbearing age and schoolchildren, as
necessary. The total goiter rate among schoolchildren decreased
from 17.4% in 1995 to 8.8% in 1997. Urinary iodine levels have
increased from 85 mcg/L in 1995 to 377 mcg/L in 1997. Nine
counties, with a combined population of 5 million people, had
achieved IDD elimination by 1997. As the end of the century nears,
we continue to track progress towards the goal of IDD elimination in
the province. While confident the problem will be solved by the year
2000, we now must consider how to sustain the achievement. The
present article considers the IDD program elements that are
necessary for sustainability, by examining them in a provincial
program.
The product - iodized salt
Soil and water in Jiangsu province contain very little iodine and
this condition will not change. Therefore, we will continue to need
additional iodine for a long time. Universal salt iodization (USI) is a
proven, cheap and effective way to supplement iodine to deficient
populations and is also safe for non-deficient people as well. To
produce iodized salt, high quality raw materials - salt and iodine -
must always be available. In Jiangsu, 90% of the salt is produced by
evaporation of seawater, 10% by mining. Although salt is plentiful,
its quality is often poor. Crude salt frequently contains impurities
such as calcium and magnesium that may be harmful to human
health. Salt for iodization purposes should be washed, dried, and
refined to reach 98% NaCl, with low or absent amounts of possible
harmful contaminants such as arsenic and mercury.
The iodine supply in China is limited. The total annual iodine
requirement for USI is about 400 tons, of which only 25% is
produced nationally. The remainder is imported, principally from
Chile and Japan. In January 1996, the Jiangsu provincial
government ceased subsidy for KIO3 purchased by salt companies.
At the same time the international price of iodine has risen because
of a large demand. Salt producers are concerned about the high
price of iodine in face of a low price for iodized salt, taxes, and the
permissible large margin for iodine loss (from 50 ppm iodine at
production to 20 ppm at households).
Jiangsu has one KIO3 plant in Lianyungang, and five
unauthorized plants in coastal cities. The latter should be registered
with the provincial Department of Medicine and Pharmaceuticals
Administration and the quality of their product monitored. They will
be an important source of KIO3. A reasonable pricing and taxing
mechanism should be established, and should be supported by
effective legislation.
At present, all salt producers and distributors are involved in the
USI program. Iodization is still carried out manually, and the
necessary quality control and supervision have been difficult to
implement. It will be more effective to advocate and support
modernization of the salt industry so that a relatively small number of
large producers compete to produce high quality iodized salt, rather
than to provide iodization facilities to hundreds of small producers.
We are now prepared to set up eight modernized salt iodization
factories in the province, aided by World Bank loan and provincial
funds, expected to be operable by the end of 1998. By then all salt
producers and distributors will be involved in an effectively operated
system.
Current regulations require exclusive use of lined or laminated
bags no larger than 50 kg, to minimize the use of hooks during
loading and unloading. The packaging should be made of
impervious material. Appropriate packaging is critical to quality
assurance. Salt producers must understand that investment in better
packaging will pay off in terms of lower iodine losses. Better
technology is needed for packaging and sealing, to improve
efficiency, longevity and price. Salt producers need to understand
that appropriate packaging during production is essential to stability
of iodized salt.
Distributors at the county level repackage the 50 kg sacks to 1
kg or 0.5 kg packets. The iodized salt is re-mixed during re-
packaging to ensure homogeneity and consistency. A semiautomatic
system for mixing, weighing, packaging, sealing and re-packaging on
one assembly line has been developed in Jiangsu. Preprinted small
packaging material contains information about the ingredients, the
type of salt, its iodine concentration, the concentrations of other
contents, the names of producers, trademarks, batch number, anti-
forge logo, and messages about IDD and the purposes of iodized
salt. After packaging, the small packets are labeled with the dates of
production and expiration (usually three months).
An effective internal quality control system among salt
producers and distributors was set up in Jiangsu in 1995. Every salt
company had its own titration laboratory, and its quality monitored by
the provincial salt management department. All lab technicians were
trained at a provincial course. Meanwhile, a rapid salt test kit was
developed and distributed commercially. Routine batch testing of
salt is performed by all producers. Before releasing their product,
they titrate the contents of iodine, and will re-mix or adjust the iodine
if not adequate.
Some non-iodized salt enters from the black market. Jiangsu
has rich resources of salt, both mined and solar, and some is
produced and distributed illegally. In the areas with salt, people have
traditionally obtained their salt free by simply going to the fields or
mines and getting it, and there may be no salt to sell in the shops. It
has been difficult for the government to suppress these illegal
markets. Therefore, in these areas, the salt companies distribute
iodized salt directly to households. This is a successful example of
salt market management.
The Process
Implementing an IDD elimination program with USI involves
many social sectors and includes a broad spectrum of activities, such
as political mobilization, commitment to public health evaluation,
surveillance, technology and laboratory quality assurance. To
facilitate tracking progress, the following program elements must be
considered: policy and advocacy, regulation and enforcement,
laboratory capacity, IEC, and management and program
administration.
Policy and advocacy - The process of eliminating IDD in
Jiangsu demonstrates how a scientifically defined public health
problem can be transformed into a politically recognized and
accepted issue upon which the full influence of government and the
people can be brought to bear. Our province will venture to act more
broadly and more aggressively to offer its people the prospect of
achieving their full intellectual potential unhampered by iodine
deficiency.
Advocacy should be renewed annually, by specific events such
as provincial advocacy meetings. Policy makers must always
remember that IDD elimination is not a temporary responsibility of
this generation but will remain a need for all society for many years.
Useful lessons come from the Schistosomiasis Control Program, a
very successful public health program started in the 1950's. By the
early 1980's, it received less emphasis and advocacy, and many
outbreaks occurred on a large scale in some places, even though
schistosomiasis had been declared as eradicated. By the late
1980's, the provincial government re-emphasized to the population
that schistosomiasis was still present and threatened human health
as well as agricultural and economic development. Since then, a
sustainable mechanism has been established and schistosomiasis is
again under control. However, the lapse resulted in increased
expenditure by the government and loss of productivity.
Currently, at the end of each year, the office of EDC organizes
an inspection to address the achievements or weak points in the IDD
program at the relevant provincial sectors, municipalities, and some
counties. An evaluation report is then submitted to the vice-governor
who then annually convenes leaders from the municipal and relevant
sectors to discuss the IDD elimination program for the next year. It
is highly recommended that documents designating duties be signed
by the appropriate vice-governor and vice-mayor and down the chain
to township leader, to share responsibilities as currently done in the
schistosomiasis control program. Sustainability requires
development or continuation of policies on salt pricing, including the
tax component, direct distribution of salt to households, and financial
appropriations for routine monitoring, surveillance, evaluation, and
salt market management.
Regulation and enforcement - An effective salt iodization
program must be supported by legislation. Currently, the National
Food Hygiene Law, the National Regulations on Edible Salt
Iodization as a Means for Eliminating IDD, the National Regulation
on Salt Administration, and provincial ordinances and Ministry actions
require the following: USI for both human and animal consumption
throughout the country; KIO3 added to salt at 50 ppm iodine/kg salt,
to provide 40 ppm at factory outlets, 30 ppm at retail outlets, and 20
ppm at households; technical standards for salt processing,
iodization, re-packaging and labeling; a system of quality control and
monitoring, with designated responsibilities and regular mandatory
reporting of results; licenses for salt producer, packager, re-
packager, and retailers; and enforcement and penalties for
noncompliance. Currently salt pricing, taxing, KIO3 production,
management, and responsibility for the cost of salt monitoring are not
included, and should be added in the next revision. Laws and
regulations are enforced regularly and constantly, especially by the
health and salt sectors. An enforcement team was established in
1996 in the Departments of Health and Salt Administration.
Inspectors take samples to the laboratory for iodine analysis, and
enforcement action is taken when noncompliance is discovered.
Laboratory capacity - An important component in IDD
elimination programs is monitoring and surveillance of the biological
impact of IDD, as well as the satisfactory quality of iodized salt. This
information is vital to properly guide policy makers and program
managers. The laboratory, both in health and salt sectors, plays a
key role in providing data on the efficacy of the program efforts, USI
progress, and eventual verification of achieving the goal of IDD
elimination.
The current laboratory system already has the basic elements
to provide these services. The current need is to strengthen the
laboratory capacity. Health sector laboratories at provincial,
municipal, and county levels can perform salt and urinary analyses,
but the capacities are diminished because of outdated equipment
and the setting up of new laboratories. Training and updating of
technicians in both sectors is still needed.
The provincial laboratories can also carry out blood spot TSH
assays (IRMA). Diagnostic kits are available commercially but ELISA
equipment is needed, because the sensitivity and stability of current
commercially obtained IRMA diagnostic kits could not meet the
needs of IDD surveillance. Chinese diagnostic kits are not available
and imported kits are not affordable.
Information, health education, and communication -
Nutrition messages reach consumers through many channels, to
convince them that the IDD control program will have tangible
benefits for them, especially for their children. In schools, teachers
tell students about IDD and its control and students carry the
knowledge to their parents and the rest of society. Professionals
from the provincial departments of health and education compile the
chapter titled "IDD and its Elimination" for insertion in the health
education textbook for elementary and middle-school students.
IDD Day (May 5, every year since 1994) plays a key role in
educating the public about the hazards of IDD and the importance of
its control measures, and also in mobilizing leaders. At that time,
leaders from the government and relevant sectors educate and
inform the public about IDD, and professionals elaborate on how IDD
adversely affects intelligence, school performance, success in life,
national productivity, and competitiveness. IDD reaches the
classroom through salt testing, introducing IDD as parts of math,
geography, and chemistry. The 1996 National Entrance Examination
to University included a question about IDD in the chemistry test.
Many students were puzzled but later found the correct answer.
All counties have a salt hot-line phone. Anyone who finds
unauthorized salt may dial the phone and get a reward. This type of
information, and that on sales and monitoring have not yet been
used to target communities, but they may prove valuable for this
purpose.
Input for comprehensive health education strategy should come
from a number of sectors. Their different messages should be
combined into a comprehensive and coordinated plan that makes full
use of the wide range of resources working on IDD. This strategy
should be prepared annually and changed with shifts and demand.
Management and program administration - The structure,
Figure 1, shows a direct line of authority from the provincial leading
group to the municipal, through the county leadership down to
township organizations. Reports and information can proceed
upward from township to provincial through successive levels, and
evaluation reports and information can feed back downward.
Leading groups are chaired by a vice-governor or counterparts at the
municipal and county levels, and consist of leaders from relevant
sectors. Offices of EDC work as their serving offices, often located
in health sectors under the direct leadership of chairpersons of the
leading group, responsible for coordination, guidance and support for
all sectors participating in the IDD program. Representatives in all
sectors are able to bring issues of suggestions to the office of EDC
or directly to the chairperson of the leading group. Each sector has
its own hierarchical structure that provides a managerial framework
for its daily functioning.
Progress
To trace progress towards the program's goal, the provincial
department of the EDC set up a county-based monitoring system to
measure progress indicators monthly, and also a province- and
municipality-based surveillance system to measure impact indicators
every two years.
The process indicators are as follows: (1) factory, repackaging,
and warehouse level - 95% of the edible salt should be claimed as
iodized and 90% effectively iodized; the monitoring process should
be 95% adequate internally and 90% externally; (2) retail level - 90%
should be effectively iodized; and (3) household level - 95% of the
salt should be iodized, 90% effectively. The impact indicators are
the same as recommended by the ICCIDD/WHO/UNICEF guidelines
(IDD Newsletter 10(4):37, 1994): (1) salt iodization, > 90% of
households consuming effectively iodized salt; (2) urinary iodine, <
50% below 100 mcg/L, and < 20% below 50 mcg/L; (3) total goiter
rate, < 5%; and (4) neonatal TSH, < 3% having levels > 5 mU/L
whole blood. The first two, salt iodization and urinary iodine, are
mandatory indicators; the total goiter rate and neonatal TSH are
optional.
The county-based monitoring system maintains a continuous
check on the iodine content of salt. LQAS was used for sampling,
interpreting, and evaluating iodized salt quality at the production,
distribution, and household levels. Based on the Provincial
Surveillance Plan, developed in 1996, each county collects 25 salt
samples for testing by titration and rapid test kits from each of the
following: (1) producers - titration monthly, rapid test routinely (not
every county has producers); (2) re-packagers - titration monthly,
rapid test routinely (every county has only one re-packager); (3) retail
outlets - rapid test monthly, titration quarterly; and (4) households -
titration monthly. All monitoring results from counties are reported
monthly to packagers/re-packagers, municipal and provincial
departments of EDC, and in turn quarterly to provincial departments
from the municipal departments. At the end of each quarter, the
provincial department sends the evaluation report to the relevant
provincial sectors and the office of EDC (which will report to the vice-
governor if necessary), provides feedback to municipal and county
departments, producers/re-packagers, and disseminates information
to the public through the media. At the end of the year, the
provincial departments submit an evaluation report to the Ministry of
Public Health in Beijing and the National Center for EDC in Harbin.
Surveys were conducted in 1995 and 1997. Each selected 40
pupils in 30 schools randomly according to population size. All
pupils' thyroids were examined by palpation and ultrasonography,
their family salt was tested for iodine content by titration, and 12
pupils per cluster submitted urine samples for iodine analysis. A
questionnaire was also sent to 20 pupils at the 5th grade level and
10 teachers per cluster, to assess their knowledge about the
consequences of IDD and control measures. Each municipality
conducted surveys in 1995 and 1997 with the same methodology.
At present, two quality assurance systems exist, external and
internal. In the latter, established in 1996, each salt producer or re-
packager has his own titration laboratory. A provincial salt quality
testing center is responsible for quality control of all laboratories. In
the external quality assurance system, several sectors, such as the
Technical Supervision Department and the Commercial Department
are involved in collecting salt samples for salt iodine testing, although
the health sector has the primary responsibility for this task.
Different sectors use different sampling methods. The health sector
uses LQAS, while the salt sector uses a composite sampling method.
The Technical Supervision Department and the Commercial
Department only collect about two or three samples from the whole
lot. The external quality assurance system should be coordinated
and information shared, and LQAS is strongly recommended as the
standard sampling procedure for all sectors.
Neonatal TSH is a sensitive indicator for identifying the
existence and magnitude of IDD in many developed countries and in
some developing countries. If a country has a universal neonatal
TSH screening in place, the recall level will be proportional to iodine
deficiency. In Jiangsu, a neonatal screening program was started in
the late 1980's, conducted both in hospitals and at epidemic
prevention stations. It is still not universal although it is supported by
the law, which is called the "National Law on Woman and Infants
Protection," passed several years ago. Different screening methods
make it very difficult to share results. Coordination between
hospitals and the epidemic prevention stations, and health education
for every pregnant woman, are needed.
Recently, iodine-induced endemic goiter has become an
increasing concern in China. In Jiangsu province, we found an area
of 4,000 square kilometers with iodine excess, with a population of
2.4 million. In it the iodine content is as high as 300 mcg/L in
drinking water and the urinary iodine reaches 1500 mcg/L in the
adult population. The total goiter rates in the schoolchildren are from
10% to 40%. So far, 91 counties in eight provinces report iodine
excess, with some 16 million population at risk in China. Iodine
excess should always be kept in mind, because it can be harmful to
human health, but the extent of its public health threat is much less
than that of IDD.
Summary
Jiangsu province is one of the most developed provinces in
China, with a population of approximately 70 million. It should
achieve the goal of sustainable elimination of IDD before other
provinces in the country. The virtual elimination of IDD in Jiangsu
province means that every newborn will have a chance to reach his
or her full intellectual potential. A self-sustainable mechanism to
deliver optimal iodine on a daily basis will bring high social and
economic returns on the investments of the people.
SUSTAINING THE VIRTUAL ELIMINATION OF IODINE
DEFICIENCY DISORDERS IN NIGERIA AND THE WEST AFRICAN
SUBREGION. John Egbuta and Nimal Hettiaratchy, ICCIDD West
Africa Subregion, University of Jos, and UNICEF, Nigeria
In Nigeria's population of 114 million people, the prevalence of
goiter is above 20% (1993), with the highest endemicity in the mid
southern part of the country stretching from east to the west (1,2).
Goiter is not a serious problem in the coastal areas of southern
states but becomes a public health concern in the hinterland up to
latitude 8 towards the north. The IDD problem in the distant
northern states is not as severe as in the midlands where the goiter
prevalence reaches 45% in some areas (see IDD Newsletter
12(2):27, 1996).
Iodine deficiency disorders are an ecological problem arising
from a long-standing and continuous loss of iodine from the soils and
water. The affected area in Nigeria lies within the tropical rain forest
belt with annual rainfall measuring up to 2000 mm. The continuous
rain over a period of 5-7 months in the year leaches iodine from the
soil, a process hastened by the undulating topography. The common
food staple in this belt is cassava, a carbohydrate root tuber with a
high concentration of thiocyanic acid. Thiocyanic acid has been well
documented as a goitrogen that competes with iodine for uptake by
the thyroid gland, and may also contribute to the severe IDD in this
area.
Universal salt iodization
Nigeria consumes 450,000 to 550,000 metric tons of salt per
annum, computed at 5-7 g/day per capita. About 600,000 metric
tons are imported annually. Dicon PLC imports 400,000 from
Australia and Brazil, NASCON 45,000 from Spain, and New Nigerian
80,000 from Egypt and Spain; others (John Holt, Columbia) produce
60,000, and local small scale producers account for 10,000.
The initial effort to iodize the salt in Nigeria started in 1992 with
discussions between UNICEF, WHO, the Standards Organization of
Nigeria (SON), and the Federal Ministry of Health. A regulatory
instrument banning the importation of non-iodized salt into Nigeria
came into force in 1994. Nigeria has a manageable number of salt
industries which has made compliance and enforcement of the
regulation relatively easy. In this situation, Nigeria is better placed
than the many other West African countries that each have an
average of 10-20 different salt industries and processors. In addition
to this relative advantage, about 80% of the countrys total salt
consumption is imported by the Union DICON Salt PLC and it has
been iodized at source in Brazil or Australia.
Much more needs to be done in West Africa because iodized
salt consumption is very low in most countries. Household
consumption of iodized salt in several others African countries was
reported as follows in the 1997 Progress of Nations: Sierra Leone,
75%; Benin, 35%; Chad, 31%; Burkina Faso, 22%; Ghana, 10%;
Senegal, 9%; Niger, 7%; Guinea, 0%; Guinea Bissau, 0%; Liberia,
0%.
Some countries in the subregion, especially Nigeria and
Cameroon have already attained nearly 100% salt iodization level
(7). While this is commendable, serious efforts must be made to
sustain the current iodization levels in both countries. Countries in
the subregion have porous borders that permit non-iodized salt to
move in and out. Iodized salt packaged in Nigeria also filters as far
as Cameroon, Niger, Chad, Benin, and Burkina Faso. The issue,
therefore, is how to establish a framework, or strengthen an existing
one, to ensure the constant movement and distribution of iodized salt
in the subregion. In July 1994 the Abuja meeting of ECOWAS
agreed that all member countries should immediately adopt a
resolution to iodize all domestic salt in West Africa. That resolution
was passed four years ago and only Cameroon and Nigeria have
shown much progress.
Lessons learned
Before the campaign to promote awareness of the
consequences of iodine deficiency, many myths and beliefs were
associated with goiter and cretinism in Nigeria. Enlargement of the
thyroid tissues (goiter) was attributed to witchcraft. In certain areas
goiter was considered to be a symbol of beauty; a woman without it
was not beautiful and considered to be under a curse. These beliefs
are fast disappearing in the face of a very strong awareness
campaign on the consequences of iodine deficiency. The use of the
media, in all its ramifications, has contributed largely to the
behavioral changes accompanying the campaign's success.
The control of iodine deficiency disorders in Nigeria began in
1974 but advocacy was restricted to government agencies. This
approach yielded no results for almost 20 years. The involvement of
the organized private sector in the control of IDD was the needed
catalyst to move the program forward. In all the countries in West
Africa, salt importation and processing are not the affairs of
government but belong to the private sector. In Nigeria, for example,
as soon as the three major salt producing companies became
convinced of the seriousness of IDD, they immediately saw the
importation of iodized salt as a patriotic responsibility towards the
reduction of a rising trend in infant mortality in the country.
The amount of resources allocated for these projects on a
yearly basis is usually small and in Nigeria it was decided to handle
the entire program against micronutrient deficiencies - iodine, iron,
and vitamin A - in phases, to give maximum attention to each. In
Nigeria, the Micronutrient Deficiency Program initially focused on IDD
and between 1993 and 1994 every effort was directed to it. Maximal
funding, time, and energy were plowed into IDD control and within 18
months a successful framework for its elimination had evolved.
Beginning in 1995, efforts and attention were given to vitamin A
deficiency and later in 1997, the control of iron deficiency anemia
took center stage. This staggered approach is worth sharing with
other countries within the subregion.
For the future
The two largest countries within the subregion, Nigeria and
Cameroon, with a combined population of about 140 million people,
have mounted successful programs for IDD control. To forward the
sustainable elimination of IDD in the West African subregion, the
following are proposed:
1. an inventory of salt industries in the subregion and a
possible networking of their distribution channels to ensure maximum
outreach;
2. revisiting the ECOWAS endorsement of monitoring universal
salt iodization in all member countries and ensuring full compliance;
3. UNICEF providing KIO3 to key salt industries in West Africa
at a subsidized cost; and
4. ensuring a steady supply and movement of iodized salt at
international and national levels.
References
1. Egbuta J 1993 UNICEF Consultancy Report on IDD
Situation in Nigeria.
2. Gutekunst R 1993 Report of consultancy on the use of
ultrasonography for IDD survey in Nigeria.
3. Lantum and Meftah 1996 ICCIDD Multicenter study report
on the emergence of hyperthyroidism in Africa.
4. Mannar V, Egbuta J 1993 Report of rapid survey of salt
sources in Nigeria (for UNICEF).
Table 1. Prevalence of goiter in selected West African countries
Total Population Prevalence of
S/N Country (million) goiter (percentage)
1 Niger 9.4 9
2 Sierra Leone 4.2 7
3 Guinea-Bissau 1.09 19
4 Guinea 7.5 19
5 Liberia 2.24 6
6 Mali 11.1 29
7 Nigeria 115 20
8 Burkina Faso 10.7 16
9 Ghana 17.8 10
10 Benin 5.5 24
11 Cote D'Ivoire 14 6
12 Senegal 8.5 12
13 Cameroon 13.6 26
14 Togo 4.2 22
Source: State of the Worlds Children Report, 1998.
REPEATED LOW ORAL DOSES OF LOCALLY PREPARED
IODIZED OIL FOR IODINE DEFICIENCY IN THAILAND. R.
Suwanik, R. Pleehachinda, V. Boonnamsiri, C. Pattanachak, S.
Pattanachak. S. Chongchirasiri, N. Tojinda, T. Jaipetch, B.
Amorngitticharoen, N. Putrasreni, S. Tantipiyaskul, and I. Buttfield,
Nuclear Medicine Division, Department of Radiology, Faculty of
Medicine, Siriraj Hospital, Mahidol University, Bangkok and
University of Adelaide, Drug and Alcohol Services Council, Australia.
Iodized oil, either by injection or orally, is a well established
technique for controlling severe iodine deficiency. Previous studies
have usually used single large doses. Iodine-deficient subjects may
be very sensitive to acute or chronic iodine excess that can cause
transient inhibition of intrathyroid hormone biosynthesis, fail to reduce
goiter size, transiently increase serum thyroid stimulating hormone
concentration, exacerbate goiter size, and produce thyroid
autoantibodies. These effects may be more frequent and severe
after oral administration of iodine because its rapid deiodination in
the digestive tract gives higher levels than those from intramuscular
injection. For this reason, Tonglet et al. (1) have advocated small
doses of oral iodized oil. In the present study, we explored the use
of an iodized oil produced in Thailand, given in small oral doses at
frequent intervals.
Our study took place in Mae Hong Son, a narrow strip of
rugged mountain highlands in northwest Thailand, adjacent to Shan
State in Myanmar. The area is fairly isolated and becomes
impassable during the rainy season. The prevalence of goiter was
known to be persistently high: surveys from 1989 to 1993 estimated
35 to 44% in children. This rate was considerably higher than that in
other parts of Thailand, possibly because of transportation difficulties
and substandard living conditions. The population of slightly less
than one million consists mostly of hill tribe people as immigrant
inhabitants.
Iodized oil preparation - We developed iodized soybean oil by
modifying the method of Professor Ma Tai of Tienjin University.
Details have been published (2-4). Briefly, 90 ml of 57% hydriodic
acid (HI, E. Merck) were added dropwise to a stirred mixture of 24 g
of red phosphorus and 330 g of resublimed BP iodine (Roques
Clinic, France) in a two-neck round bottom flask. The dried HI gas
was formed and reacted with 300 ml of soya bean oil in three
Erlenmeyer flasks connected in series, for 3-5 hours. After
iodination, the oil became dark brown and very viscous. To remove
free iodine, 100 ml of 8% sodium metabisulfite solution were added
with constant stirring, and this step repeated many times. The water
was removed by extracting the solution with 60 ml of absolute
ethanol until semi-transparent iodized oil was obtained.
Esterification was undertaken by adding iodinated oil dropwise
to a stirred mixture of 400 mg metallic sodium and 100 ml absolute
ethanol at room temperature. The reaction mixture was refluxed for
30 minutes and stirred overnight, then neutralized with 6 N HCL.
Excess acid, alcohol, and salt were removed by washing several
times with hot deionized water. The oil layer was eventually
separated and dried with absolute ethanol. The solution was
evaporated and dried under a vacuum pump, leaving the products as
a light yellow semi-transparent esterified iodized oil. Its total iodine
content was 358 mg/g (458 mg/ml), about 95.4% that of Lipiodol, and
it contained no free iodine. Infrared spectrophotometer (IR), nuclear
magnetic resonance spectrometer (NMR) and gas chromatography
(GC) established its structure. The product was very stable. It
compared favorably with Lipiodol, providing the same pattern of daily
urine iodine excretion, and showed no toxicity on administration to
mice (5). The iodized oil (458 mg I/ml) was diluted with soya bean
oil, then subdivided into 15 ml plastic bottles to give a final
concentration of 40 mg iodine per 20 drops (1 ml).
Experimental design - 106 women volunteers of 14-45 years
of age in Baan Huay Khan village, Mae Hong Son Province, were
assessed for goiter according to the new WHO/UNICEF/ICCIDD
classification (6) and thyroid size recorded by the surface outline
method of MacLeenen and Gaitan (7). Urine and blood samples
were collected from women before ingestion of iodized oil in the pre-
test period, and further urine samples at varying periods of time in
post-test assessments.
For the initial course, 10 drops of iodized oil (20 mg of iodine)
were squeezed from the plastic bottle into the subjects mouth by
trained observers (Figure 1). The patients swallowed the oil drops
automatically. This dose schedule was repeated every four months
in the first year. In the second year, the dose was increased to 20
drops (40 mg of iodine) of iodized oil three times a year. The pre
and post-test goiter rates were evaluated by palpation and
measurement of the surface area by planimeter or graph paper
estimations. Thyroid 131I uptake and biochemical tests including the
urinary excretion of iodine were performed routinely at each
examination. We measured iodine content in various samples by
standard methods (8,9), T3, T4 by radioimmunoassay, serum TSH by
an IRMA, thyroid 24 hour 131I uptake with miniature equipment (10)
and thyroid microsomal and thyroglobulin antibodies by
hemagglutination methods (11).
Five girls in Bangkok, acting as controls, received doses
varying from 20, 50, 100 to 200 mg of iodine and their urine was
analyzed for iodine.
Baseline iodine deficiency in Mae Hong Son - The iodine
content of vegetables, soil, and water were as low as 50%, 16%, and
7%, of the respective amounts in samples from Bangkok. The
following list compares iodine content, in mcg/kg, of several
vegetables, first for Mae Hong Son, then Bangkok: celery: 243,
468; cabbage: 142, 260; Cha-om: 262, 520; cucumber: 200, 290.
The iodine content of soil in Mae Hong Son was 286 mcg/kg,
compared with 1780 in Bangkok. Water from Mae Hong Son was
8.5 mcg iodine/L compared with 12 for Bangkok.
The median urinary iodine for 72 subjects in Baan Huay Khan
(Mae Hong Son Province) was 71 ( 38.1) mcg/g creatinine. Fifty-
seven percent of samples were below 100 mcg/g, 28 below 50, and
4% below 25. Median values for 60 serum samples were T3 109.5
ng/dl, T4 7.2 mcg/dl, and TSH 2.1 mU/L. The median 24 hour 131I
uptake of 43 boys and girls in the village was 70.3 15%. Goiter
was widespread in the village and 3 young adult cretins (1.5%) were
noted.
Effects of iodine - Before treatment, 95% of the women had
goiter. After one year of treatment, 78% were goitrous. The
fractions in group 2 and group 1 goiter decreased correspondingly.
After the second year, the goiter prevalence had decreased to 63%,
and by the sixth year, to 17%. The annual rate of decline in
prevalence after year 1 was 17%, 15% after year 2, and 11.5% for
each of the following four years.
After two years, the urinary iodine concentration rose from a
pretreatment median of 72 mcg/L to 127. In the same interval, the
T4 increased from 7.2 mcg/dl to 8.5 and the total T3 from 109 ng/dl to
120. The serum TSH concentration remained essentially the same,
going from 2.1 mIU/L to 1.9. After the first two years of the program,
some of the subjects received 200 mg oral iodized oil every six
months from the Ministry of Health. The serum T3 and T4 remained
essentially unchanged, and the TSH remained within the normal
range. The urinary iodine increased from 191 mcg/L at the
beginning to 935 but the latter samples were collected shortly after
administration of iodized oil.
We followed about 10 subjects at successive intervals after the
administration of 40 mg of the iodized oil and found the following
urinary iodine concentrations: day 1, 19,712 mcg/L; day 2, 9,835;
day 3, 8,575; day 7, 6,305; day 14, 5,848; month 1, 3,992; month 2,
2,020; month 3, 307; month 4, 119; month 5, 53.4; month 6, 23.3.
We also measured urinary iodine excretion in several subjects in
iodine sufficient Bangkok after ingesting varying doses, from 20 to
200 mg iodine. The pretest values ranged from 142 to 182 mcg/L.
The four doses contained 20 mg iodine, 50, 100, or 200. The iodine
excretion in the first two weeks was parallel to the size of the dose.
By two months urinary iodine concentrations ranged from 156 mcg/L
(20 mg dose) to 392 (200 mcg dose). At four months, the
concentrations were as follows: 196 mcg/L (20 mg dose), 200 (50
mg), 216 (100 mg), and 269 (200 mg).
Advantages of low doses of oral iodized oil - In vulnerable
iodine deficient areas such as Mae Hong Son, iodized oil is needed
at least for initial short-term IDD control, in addition to iodized salt
and iodized water. In urgent situations, a few ml of oral iodized oil
given to women prevent new cases of neurological cretinism in their
subsequent offspring. For administration, women formed a row and
oil was instilled directly into their open months, in drops, not in
capsules, because this ensures that it was really swallowed. Oral oil
requires no injection and, therefore, carries no concern about
contracting AIDS or other blood-borne diseases. Appointments can
be made for large numbers of people and the mass administration
requires only one or two professionals at a health post. More than
100 people can be treated per hour.
The program of multiple small doses of iodized oil has several
advantages. It may imitate nature by providing smaller, near
physiologic doses during periods of iodine deficiency, so that
induction of hyperthyroidism is avoided. The repeated installations
may be instrumental in emphasizing to villagers the importance and
value of the treatment. This oil can be synthesized within the
country at 20% the price of imported capsules and 50% the price of
imported ampoules, providing great savings in foreign currency.
Cretinism is prevented if the oil is given before conception, and this
method can be used throughout the subjects reproductive life. The
program of administration is easy, can be started immediately, and
buys time while working on the more complex establishment of
iodized salt or water. Refrigeration of the oil is not required. Neck
palpation for goiter survey can be carried out at the time of the oil
administration.
Iodine repletion from the iodized oil can be extended and
maintained with iodized salt and iodized water, both of which are
effective and inexpensive. The benefits of iodized salt are well
known. According to Thai culture, drinking water is always ready for
guests or passersby at every house and thus iodized water is also
easy to distribute.
Data comparing different doses show that most iodine in the
large doses, e.g., 200 mg, is lost in the urine within the first several
days. High iodine levels are sustained for some time, perhaps
making the subject more vulnerable to iodine-induced
hyperthyroidism. At one year we found a significant reduction in
goiter size after oral administration of 20 mg iodine as a single dose.
Later the dose was increased to 40 mg as iodine every four months.
The reduction in goiter prevalence reached 17% in the sixth year in
contrast to patients who had much larger doses. Our findings agree
with those of Tonglet et al. (1), but we gave divided doses three
times a year. An obvious effect of smaller amounts of iodized oil by
this method is that it motivated women and their families to want
iodine supplementation.
The advantage of a low dose of iodized oil may be that it
avoids iodine's inhibitory effects. At physiologic levels, iodine may
be trapped by the thyroid and form hormone early in iodine treatment
(1), thus replenishing thyroidal iodine more effectively without waste
by the urine. For example, in this study, the regression was 17.4%
in one year, in comparison to a reduction of 11.5% in Uttaradit
province after 240 mg iodine as iodized oil. In another trial in Nan,
with extra large doses of iodine of 980 mg, the goiter prevalence was
decreased by 31%. From this we suggest that the effect of iodized
oil could be dose-dependent, in which the goiter is similarly sensitive
to small or large doses of iodine but the action is more prolonged in
accordance with the magnitude of the iodine dose.
The acceptability of the iodized oil by women was excellent.
They asked for repeated iodine treatment because they saw that it
made their thyroids smaller. We extended the treatment to include
pregnant women. The smaller doses may be especially appropriate
for them because the fetal thyroid and brain are particularly sensitive
to iodine deficiency.
In the years following the initiation of this study, 1994-1997, the
Ministry of Health provided capsules of 200 mg iodized oil twice a
year in Mae Hong Son. Of 240 subjects, 8 (1.7%) had developed
hyperthyroidism and several had transient hypothyroidism. We found
no such problems with the smaller doses. In another comparison in
Kam Cha Ee in northeastern Thailand, where 100 mg iodine was
administered twice a year for four years, the goiter prevalences were
respectively, 16.2, 18.9, 20.9, and 21.9% for the four years. The
failure to reduce goiter rate may stem from increased TSH (12).
Also, with smaller doses of iodized oil, we found circulating
antibodies in only two of 106 subjects. In contrast, of 627 subjects
receiving 200 mg capsules twice a year for three years, 36 had
antibodies to thyroglobulin, and 14 to thyroid peroxidase.
The cost of synthesizing 900 ml of iodized oil (458 mg
iodine/ml) was about 1600 bahts (1 US $ = 57 bahts at time of
study). The cost of 1 ml was 0.22 bahts (US $0.0038) per person.
In contrast, imported iodized oil by the same dilution and for an equal
number of subjects was 0.44 or 1.00 bahts/person for an ampoule or
a capsule, respectively.
Summary - We prepared iodized soya oil in Thailand and gave
it to 106 women in doses of 20 mg iodine every four months for one
year, then 40 mg every four months for the following five years, in a
severely iodine-deficient area of north Thailand. The goiter
prevalence decreased from 95% to 78% in the first year to 63% in
the second year and 17% at the sixth year, and low urinary iodine
concentrations returned to normal. The oil was easy to administer,
well accepted and not accompanied by iodine-induced
hyperthyroidism or cretinism. The reduction in goiter rate and the
cost appeared better than in other programs in Thailand where larger
doses of oral iodized oil were given. These low doses may be more
effective because they inhibit the thyroid for a shorter period of time.
References
1. Tonglet M, Bourdoux P, Tshilembi M, Ermans AM 1992
Efficacy of low oral dose of iodized oil in the control of iodine
deficiency in Zaire. N Engl J Med 326:236-41.
2. Jaipetch T, Pattanachak C, Chongchirasiri S, Pleehachinda
R 1986 Synthesis of iodized oil. In: Vichayanrat A, Nitiyanant W,
Eastman C, Nagataki S (eds). Recent Progress in Thyroidology,
Bangkok, Proceedings of the 3rd Asia and Oceania Thyroid
Association Meeting, pp 426-39.
3. Jaipetch T, Pattanachak C, Chongchirasiri S, Pleehachinda
R, Suwanik R 1986 Synthesis of iodized oil. Thai J Med Assoc 2:87-
91.
4. Jaipetch T, Pattanchak C, Chongchirsiri S, Pleehachinda R,
Suwanik R 1994 Preparation of seed iodized oil. Siriraj Hosp Gaz
46:939-42.
5. Chaisomboonpan T 1995 Non-toxicity of the iodized soya
bean edible oil. Report of Department of Medical Sciences, i.
6. WHO, UNICEF, International Council for the Control of
Iodine Deficiency Disorders 1994 Indicators for assessing iodine
deficiency disorders and their control through salt iodization. WHO,
Geneva.
7. Mac Lennen R, Gaitan E 1974 Measurement of thyroid size
in epidemiologic survey. In: Dunn J, Medeiros-Neto G (eds).
Endemic Goitre and Cretinism: Continuing Threats to World Health.
Washington, PAHO Sci Publ #292, pp 195-7.
8. Zak B, Willard HH, Myers GB, Boyle AJ 1952 Chloric acid
method for determination of protein bound iodine. Analytical
Chemistry 24.
9. Dunn JT, Crutchfield HE, Gutekunst R, Dunn AD 1993 Two
methods for urinary iodine in urine. Thyroid 3:119-23.
10. Riccabona G 1980 Thyroid cancer and endemic goitre. In:
Stanbury JB, Hetzel BS (eds). Endemic Goiter and Endemic
Cretinism, New York, Wiley Medical Publications, pp 340.
11. Thymune M, Thymune T Hemagglutination kits for the
detection of thyroid microsomal and thyroid antibodies. 1994 Murex
Diagnostics, Dartford, England, May 1994.
12. Vongsatala P. Personal communications to the authors.
ABSTRACTS
CONSEQUENCES OF IODINE DEFICIENCY IN CATTLE IN SOME
REGIONS OF THE CZECH REPUBLIC. J. Kursa, I. Herzig, V.
Kroupova, P. Kratochvil, J. Travnicek, University of South Bohemia,
and Veterinary Research Institute, Brno, Czech Republic. Scientia
Agriculturae Bohemica 28:105-117, 1997.
The authors assessed the prevalence of goiter in calves born in
parts of the Czech Republic, particularly southern and western
Bohemia, between 1988 and 1997. Of 1,355 calves from birth to
three weeks of age in 25 herds of dairy cows, 404 (30%) had goiter,
most prominent in newborn calves. Some died at birth or shortly
afterwards, and abortions were frequent. The goiter was diffuse, and
ranged from slight enlargement to a weight of 720 grams. Big
thyroids during birth put pressure on the larynx and trachea, leading
to difficulty in breathing, problems with swallowing, heart arrhythmias,
venous congestion, and some deaths. Partial baldness and alopecia
were also occasionally noted. The authors analyzed the iodine
content of milk from herds which produced goitrous calves, finding an
average ranging from < 10 to 31 g/l. Herds with goiter had over
80% of milk samples less than 30 g/l, while herds without goiter
had 52% less than 30 g/l. Their experience is similar to other
reports in the agriculture and literature. Iodine deficiency is reported
to increase abortions and neonatal mortality among calves. Previous
authors have reported that dairy cows with goitrous calves produced
21% less milk. Other studies had shown that hypothyroidism
reduced milk production by 50-80% and supplementation with
iodinated casein increased the milk yield in cows with
hypofunctioning thyroids. The iodine content of milk decreased over
this nine year period in the Czech Republic. In the 1980's iodine
levels in milk in Moravia ranged from 140-225 g/l. These data
reflect the addition of feed mashes with iodine supplements.
Additionally, iodine-containing preparations were used for mammary
gland sterilization, and iodine deficiency was not found in the 1980's.
More recently the average iodine content in south Bohemia was
reported as from 62.5-100 g/l. The mass occurrence of goiter in
new calves has occurred only in recent years. The causes include a
limited consumption of commercial food mashes for economic
reasons, absence of iodine enrichment in local feeds, and
discontinuation of iodine in udder cleansing preparations. These
data show the importance of adequate iodine for the production of
healthy calves and adequate milk in the dairy industry.
THE INCIDENCE OF HYPERTHYROIDISM IN AUSTRIA FROM
1987 TO 1995 BEFORE AND AFTER AN INCREASE IN SALT
IODIZATION IN 1990. A. Mostbeck, G. Galvan, P. Bauer, et al. Eur
J Nucl Med 25:367-374, 1998.
This extensive study from 19 nuclear medicine centers in
Austria tracks the incidence of hyperthyroidism over an eight year
period during which iodized salt levels were changed. Since 1963,
salt in Austria was iodized at 10 mg KI (7.5 mg iodine)/kg. Because
urine contained 40-80 mcg iodine/g creatinine and goiter prevalence
was about 20%, the level of iodine in the salt was increased to 20
mg KI/kg. Approximately 414,000 patients were examined in the
cooperating institutes, which cover about two-thirds of Austria's
population of 7.86 million. Measures included clinical examination,
serum TSH and thyroid hormone levels, thyroid ultrasonography,
scintigraphy and autoantibody titers. Over the eight-year period a
total of slightly over 47,000 patients were registered with
hyperthyroidism, 75% from toxic nodules and 19% from Graves'
disease. From 1987 to 1989 the annual incidence of overt thyroid
disease was 30.5/100,000. Compared to this baseline, the relative
risk of hyperthyroidism was 1.37 in 1992, and had decreased to 1.17
by 1995. The annual incidence of subclinical hyperthyroid nodules
was 27/100,000. The relative risk was 1.64 in 1991, and 1.60 in
1995. The increase was highest in persons over 50 years old,
particularly men. The initial incidence of overt Graves' disease was
10.4/100,000, with the maximum relative risk increasing to 2.19 in
1993 and down to 1.95 in 1995. The incidence of subclinical Graves'
disease was 1.9 before 1990, reached 2.5 in 1994, and was 2.26 in
1995. The increase in Graves' disease occurred at all ages in both
sexes. This large study documents the transient hyperthyroidism
induced by iodine. Overall, the pattern was an increase in
hyperthyroidism peaking at 1-4 years and subsequently decreasing,
except that subclinical Graves' disease did not decrease appreciably.
IODINE INTAKE AND THE PATTERN OF THYROID DISORDERS:
A COMPARATIVE EPIDEMIOLOGICAL STUDY OF THYROID
ABNORMALITIES IN THE ELDERLY IN ICELAND AND IN
JUTLAND, DENMARK. P. Laurberg, K. M. Pedersen, A.
Hreidarsson, et al, Aalborg Hospital, Randers Hospital, Denmark and
Reykjavik, Iceland. J Clin Endocrinol Metab 83:765-769, 1998.
The authors compared randomly selected subjects 68 years old
from Jutland (Denmark) and Iceland, areas with low and adequate
iodine intakes respectively. The median urinary iodine concentration
was 38 mcg/L in Jutland and 150 mcg/L in Iceland. The goiter
prevalence in Jutland was 12.2% in females and 3.2% in males,
compared with 1.9% in females and 2.2% in males in Iceland (goiter
was assessed by palpation, but compared well with spot
ultrasonography). In Jutland, 9.7% of TSH values were less than 0.4
mU/L while none were low in Iceland. However, 18% of TSH values
in Iceland were above 4.0 mU/L (the normal cutoff), but only 3.8% of
those in Jutland were high. Autoantibodies were present in all
subjects with TSH's greater than 10 mU/L. The prevalence of
autoantibodies was twice as high in females as in men, and twice as
common in Jutland as in Iceland. Values for serum thyroglobulin
were frequently high (>30 mcg/L) in Jutland (females 35.3%, males
20.5%) compared with 6.3% in females and 0% in males in Iceland.
The authors emphasize the risk of hyperthyroidism in older people
with iodine deficiency, as in Jutland. The increase in autoimmune
thyroid disease in Iceland, as manifested by positive antibodies and
increased frequency of elevated TSH, is similar to that of other
countries with high iodine intake such as the United States.
In Brief......
IODINE IN PREGNANCY BOOK - This ICCIDD publication,
edited by Stanbury, Delange, Dunn, and Pandav, is now printed. An
abstract appears in this issue of the Newsletter. It discusses the
need for iodine and thyroid hormone in developing brain, thyroid
function during pregnancy, the pharmacology of iodized oil, field
observations on the effects of iodine deficiency during pregnancy and
its treatment in experimental animals and in iodine-deficient
endemias, and issues related to iodine nutrition in pregnancy
including assessment techniques and economic consequences.
Copies are available through the ICCIDD regional office in Delhi, c/o
Dr. Pandav (e-mail: pandav@iccidd.ernet.in; fax 91-11-686-3522).
ANDEAN SUBREGIONAL MICRONUTRIENT PROGRAM -
Following a meeting in May, ICCIDD is working jointly with the
Program in developing quality control for laboratories in charge of
urinary iodine analysis. Initially, this includes the five existing
laboratories in the Andean subregion, but will be extended to all
laboratories in the American region.
IODIZED WATER IN MEXICO - Dr. Pretell, ICCIDD Regional
Coordinator for the Americas, participated in a meeting organized by
the Ministry of Health with the support of SQM/Iodo.
Representatives of most Mexican states attended, giving an
opportunity to discuss the concerns of each state about iodine
nutrition. The Ministry of Health has decided to implement most of
the recommendations made by ICCIDD in its consultation last
November. There are now 18 laboratories for control of iodized salt
throughout the country. With the decentralization of IDD
management, a plan of action is being worked out in each state.
THYROMOBIL IN LATIN AMERICA - This project extends the
collaboration between ICCIDD and the E. Merck Company. Previous
surveys occurred in Europe and Indonesia. Dr. Pretell is Scientific
Director for the Latin American effort. The first visit took place in
Argentina, where Dr. Pretell attended a meeting and press
conferences with the Argentinean Federation of Endocrine Societies
and the Ministry of Health to bring public attention to IDD.
Subsequently the ThyroMobil will visit Chile, Bolivia, Peru, Ecuador,
Colombia, Venezuela, Mexico, Central America, and Brazil.
RUSSIA AND CENTRAL ASIA - Dr. Gerasimov reports on a
round table discussion held with UNICEF in July. The focus was on
ways to achieve USI. Recommendations include to develop a
regional salt map and analysis of the iodized salt industry, convene a
regional meeting for salt producers, obtain endorsement of CIS
health ministers towards IDD elimination by 2000, develop a regional
IDD newsletter, and prepare a regional communication plan. At the
meeting, Gerasimov reviewed the present IDD status and its control
in the region and made recommendations for future action.
WORKSHOP ON IDD CONTROL PROGRAMS IN RUSSIA -
This meeting took place in Moscow in June 1998, sponsored by
ICCIDD, UNICEF, USAID, PAMM, MI, and the Ministries of Health
and Agriculture of Russia. The objectives were to develop quality
control systems for iodized salt, create networks of laboratories for
biological monitoring, and strengthen management on the federal
and regional levels. Participants included technical staff responsible
for quality control in salt manufacturers, laboratories, other experts
on salt, government officials, and representatives of research
institutes. Participants and facilitators from ICCIDD included
Gerasimov and Locatelli-Rossi. After reviews, discussions, small
group sessions and strategy sessions, the group made
recommendations. These included development of specific
suggestions to regulatory groups on levels of salt iodization and
analytical controls, and recommendations for use of iodized salt,
implementation of analytical methods for iodine determination in salt,
reporting systems for effective monitoring of control programs,
systems for laboratory quality control of urinary iodine
determinations, and proposal for a national IDD survey.
BELGIUM - Dr. Delange reports an increase in Belgium's
interest in its iodine deficiency, following months and years of
advocacy by him and others. Recently, AKZO has organized
meetings on iodine nutrition, the Academies of Medicine in Belgium
have endorsed recommendations from the Iodine Committee of
Belgium (chaired by Delange), and the National Committee of
Hygiene has expressed interest in the problem of iodine deficiency.
The ThyroMobil will visit Belgium under the sponsorship of the
Ministry of Health with Delange's coordination.
DELANGE HONORED - Dr. Delange, Executive Director of
ICCIDD, was awarded the degree of Doctor of Medicine Honoris
Causa by the Research Board of the Charles University in Prague,
Czech Republic, on the occasion of the 650th anniversary of the
University's founding, by nomination of Professor Olga Hnikova,
Department of Pediatrics, in recognition of the long collaboration
between Dr. Delange and Charles University in the fields of
congenital hypothyroidism and iodine deficiency disorders.
NATIONAL IDD PROGRAM ASSESSMENT TOOL (ISPAT) -
OMNI/USAID, ICCIDD, and PAMM, through Pandav, Houston, and
Nathan, developed a national assessment tool and tested it in
Malawi in February 1998. This is a comprehensive check list on
program components, with a special focus on monitoring and
sustainability. It is now in draft form and will soon be circulated for
comments.
IODINE DEFICIENCY IN BREAST CANCER DISCUSSED IN
JAPAN - Dr. Bernard A. Eskin and Dr. Hiroomi Funahashi presented
a symposium at the University of Nagoya on "Relationship of Iodine
to Breast Cancer: Basic Science and Clinical Aspects." Dr. Eskin is
Professor of Obstetrics/Gynecology at Allegheny University for the
Health Sciences, Philadelphia, PA. He received the NIH Fogarty
Award in 1997-1998 with a Fellowship by the Japan Society for the
Promotion of Science to collaborate in Japan with Dr. Funahashi,
Professor of Endocrine Surgery at Nagoya University School of
Medicine. Japan has had adequate iodine nutrition and
concomitantly low morbidity of the common iodine deficiency
diseases related to the thyroid - goiter, cretinism, etc. Dr. Eskin and
others have found evidence that there may be extra thyroidal iodine
deficiency diseases as well. Early epidemiologic studies have shown
a link of increased breast atypia and cancer in areas of iodine
deficiency. The incidence of breast cancer has been increasing in
Japan, and there is also evidence for decreasing dietary intake of
iodine.
Both Dr. Eskin and Dr. Funahashi have observed prophylactic
and therapeutic effectiveness of iodine on induced carcinogenesis in
the rat breast, both acutely and chronically. The rat research studies
show that the degree of iodine deficiency correlates with the
mammary gland response to iodine replacement. Both laboratores
use DMBA carcinogenesis and noted pathological improvement and
reduced breast tumor mass with iodine replacement. These studies
were considered with preliminary dose response comparisons.
Studies on human and rodent tissue cultures shows similar effects.
Dr. Eskin has previously shown that the molecular configuration of
the iodine and the delivery system are important for effective
replacement. Clinical studies show that benign disease in
precancerous atypia were successfully reduced or obliterated with
specific iodine treatment, he reports. Other current protocols are
examining whether iodine provides treatment and/or prophylaxis for
breast malignancy. Dr. Eskin points out that extrathyroidal action of
iodine is an important new area for investigation. Nonthyroidal iodine
deficiency may cause difficulties that will require new diagnostic and
therapeutic methods. The changes recognized in the breast tissues
are already beginning to show clinical importance.