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,2
*
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands;
Department of Gastroenterology, University Medical Center Nijmegen, The Netherlands;
**
Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, The Netherlands; and
Department of Food and Nutrition, Faculty of Agriculture, National University of Benin, Cotonou, Benin, West Africa
2To whom correspondence should be addressed. E-mail: clive.west{at}staff.nutepi.wau.nl.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • iodine deficiency • indicators • schoolchildren • Benin
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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–4)
. Although thyroid-stimulating hormone
(TSH)3
is widely used to screen neonates for congenital hypothyroidism, there
have been doubts about its specificity in older children and adults
when assessing hypothyroidism induced by iodine deficiency
(5)
. Several studies have shown that although urinary
iodine concentrations and thyroid volumes were indicative of iodine
deficiency in the populations studied, both serum TSH and free
thyroxine (FT4) concentrations were within normal ranges
(2
,3)
. Thyroid volume, serum thyroglobulin (Tg)
concentration and urinary iodine concentration have all been suggested
as useful indicators for measuring improvement in iodine status after
iodine prophylaxis. However, all three have their own characteristics
and limitations. Normal ranges for thyroid volume have been established
(6
,7)
, but this indicator reflects long-standing
hypothyroidism and does not respond rapidly to changes in iodine
status. Serum Tg concentration is thought to respond quickly to
stimulation of the thyroid, increasing when iodine supply to the
thyroid is depleted and returning to normal levels when the supply is
sufficient. However, Tg immunoassays show large interlaboratory and
interassay variability, which makes it difficult to establish a
universal normal range and cut-off points for distinguishing
between different degrees of iodine deficiency (8
,9)
.
Urinary iodine concentration is not a direct measure of thyroid
function, but reflects recent iodine intake and thyroid hormone
catabolism. Thus, population groups, even if currently found to be in
the mildly deficient to normal range of urinary iodine concentration,
may still experience serious functional consequences of iodine
deficiency in the preceding period. As part of a study on iodine status and mental performance in schoolchildren aged 7–10 y in an iodine-deficient area of Benin, West Africa, the five indicators mentioned above were used to measure the effects of changing iodine supply on iodine status and thyroid function, both at the beginning of the study in 1995 and 1 y later, when iodized salt had become available to the population. The aim of this study was to evaluate the suitability of these indicators under conditions of increasing iodine supply by comparing their responses and examining their interrelationships.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The study was carried out in four villages in the district of Basila,
province of Atacora, in northern Benin, where prevalence rates of
goiter in schoolchildren aged 6–12 y varied from 20 to 60% (Doh, A. and Ategbo, E. A. Prévalence de la carence en iode dans l’Atakora; unpublished report, 1994). The villages had neither
electricity nor clean drinking water. The population was engaged mainly
in subsistence farming. Polygamy was common and levels of parental
education were low (Table 1
).
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The study was approved by the health and education authorities of the province of Atacora, Benin and by the Medical Ethics Committee of the Division of Human Nutrition and Epidemiology of Wageningen University. The aim of the study was explained to local administrative and traditional authorities, parents and teachers. Having obtained verbal approval from local authorities, the parents and the parents-teachers association, all children selected were examined by a physician. Several children with skin or respiratory infections, and malaria were treated. No children were excluded on health grounds.
Study design.
The study was set up as a randomized, double-blind, placebo-controlled intervention. After baseline measurements, children were stratified by school, school class and sex and subsequently matched on the basis of similar age and height-for-age. From each pair of children, one child was randomly allocated to one of two groups. The groups were then randomly allocated to receive either a dose of iodized oil (Lipiodol UF 7; 540 g I/L) or a placebo (poppyseed oil), both provided by Guerbet Laboratories (Aulnay-sous-Bois, France) and administered as a single oral dose (1.0 mL) with a Swift 7 dispenser (English Glass Company, Leicester, UK) in January 1996. The codes were broken after the completion of the final test.
In this paper we describe the performance of different indicators in a
group that had received an iodized oil supplement ("supplemented
group") and in a group that had received a placebo
("nonsupplemented group"). In addition, both groups had access to
iodized salt for the last 6 mo of the 10-mo observation period because
iodized salt (containing 
50 mg KIO3/kg salt) began to
appear in the markets in the study area alongside noniodized salt
3–4 mo after supplementation.
Somatic and biochemical indicators.
Blood, urine and anthropometric variables as well as thyroid volume were measured at baseline in October-November 1995. All measurements were repeated in October-November 1996. Additional urine samples were collected 1 wk and 5 mo after supplementation, i.e., in January and May 1996.
Venous blood was drawn from the antecubital vein, immediately followed
by the application of one drop of whole blood onto a filter paper card
(Schleicher & Schuell, grade 903; Keene, NH). These cards were
air-dried for 1–2 h and packed in polyethylene bags before being
frozen. Hemoglobin was assessed using a portable hemoglobinometer
(Hemocue, Helsingborg, Sweden). Serum samples were prepared and frozen
before transport. Casual samples of urine (25 mL) were collected
early in the morning and some crystals of thymol were added. Blood spot
cards and frozen samples of urine and serum were transported to the
Micronutrient Research Laboratory, University of Ghana at Legon, Accra,
Ghana for analysis of urinary iodine [chloric acid digestion followed
by Sandell-Kolthoff reaction (10)
], TSH in blood
spots [Spectra Screen Dried Blood TSH Enzyme Immunoassay Kit; IEM
diagnostika, Reflex Industries, Santee, CA] and serum ferritin (ELISA)
within the next 6–9 mo. Frozen serum samples were also transported to
the Laboratory for Endocrinology and Radiochemistry, Academic Medical
Center, Amsterdam, the Netherlands, for assessment of Tg (RIA), FT4
(time-resolved fluoroimmunoassay; Delfia, Wallac Oy, Turku, Finland)
and TSH (immunoluminometric assay; Brahms Diagnostica, Berlin,
Germany). The intra- and interassay CV were 3.6 and 6.4% for FT4, 2.4
and 4.5% for TSH and depending on the concentration, 6–7 and 7–10%,
respectively, for Tg.
A subsample of the sera (n = 23) was analyzed for selenium concentration at Rowett Research Institute, Aberdeen, UK using a fluorimetric assay method with diaminonapthaline complexing and an International Atomic Energy Agency blood standard (IAEA, Vienna, Austria).
Anthropometric measurements were made in duplicate. Height was measured to the nearest 1 mm, using a microtoise (Stanley Tools, Besançon, France). Weight was measured to the nearest 0.25 kg using a spring scale. Thyroid volume was measured by one investigator only (T.vdB.) with a portable ultrasound scanner (Aloka SSD 500; Aloka, Japan) with a 5-MHz transducer.
Data analysis.
Prints of the ultrasound images of the thyroid glands were examined by
a pediatric thyroidologist (T.V.) and either accepted or rejected for
inclusion in the data set on the basis of criteria pertaining to
clarity of the surface outlines and proper positioning of the gland.
Thyroid volumes were calculated using the following formula: volume of
one lobe (mL) = 0.479 x maximum thickness x maximum
width x maximum length (cm) (6)
. Body surface area
was calculated using the following formula: body surface area
(m2) = W0.425 x H0.725 x 71.84 x 10-4, where W is the weight in kg and
H the height in cm (11)
. Anthropometric
indices were calculated using Epi-Info (version 6.02; CDC, Atlanta,
GA).
The Kolmogorov-Smirnov test was used to determine whether variables
were normally distributed. Variables were log-transformed if not
normally distributed. Student’s t test was used to
assess differences between groups. The paired samples t
test was used to assess changes in the variables over time. Correlation
and multiple regression analyses were carried out to determine the
interdependence of the indicators used. Factor analysis
(12)
was applied to examine underlying structures in the
data set and determine whether the variables used could be combined
into a single or a reduced number of composite measures representing
"iodine status," as has also been done for iron status
(13)
.
All data were processed and analyzed using SPSS/PC software (SPSS-Windows 8.0; SPSS, Chicago, IL).
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Of the children, 33% had Z-scores for height-for-age <-2
SD of National Center for Health Statistics (NCHS)
reference (14)
, indicating stunted growth in this
population, whereas 17% had low weight-for-age (Z-score <-2
SD of NCHS reference). One year later, these proportions
were 33 and 20%, respectively. Older children were more malnourished
than younger children (data not shown).
Biochemical and ultrasound characteristics at baseline.
On the basis of criteria established by WHO/UNICEF/ICCIDD
(5)
, the baseline urinary iodine concentration of 0.16
µmol/L (20.3 µg/L) indicated that the study
population as a whole could be considered moderately to severely iodine
deficient (Table 2
). Mean serum TSH and FT4 concentrations were within the normal
reference range (15
–17)
, but 5% of the children had both
a low serum concentration of FT4 (<10 pmol/L) and a high serum
concentration of TSH (>4.4 mU/L). Approximately 15% of
the children had a serum FT4 concentration <10 pmol/L, and 11% of the
children had a serum TSH concentration >4.4 mU/L. Of the
different indicators measured, serum Tg concentration was significantly
correlated with all other indicators, except TSH in blood spots
(Table 3
). Serum TSH concentration was significantly correlated with all other
indicators except thyroid volume. When related to body surface, thyroid
volume measurements showed that 52% of the children had goiter, i.e.,
a thyroid volume above the upper limit of normal. Thyroid volume was
significantly correlated with body surface (r = 0.271;
P = 0.002), but not with age. The various indicators
measured showed a somewhat poorer iodine status and thyroid function in
older children than in younger children, but differences were
significant (P < 0.05) only for urinary iodine
concentration (data not shown). The mean serum selenium concentration
in a subsample of 23 children was 28 ± 12 µg/L.
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). Biochemical characteristics at end of the study.
By the end of the study period, all indicators showed significant
improvement in the study population as a whole (Table 2)
. The
proportion of children with a low serum concentration of FT4 or a high
serum concentration of TSH had decreased to 2 and 1%, respectively.
The proportion of children with goiter had decreased to 27%.
Correlations between the different variables were no longer
significant, except for the negative correlations between serum Tg and
urinary iodine concentration and between thyroid volume and serum TSH
concentration (Table 3)
.
Factor analysis was carried out to determine whether one or more
underlying latent variables could be identified and thus whether the
variables used in the study could be combined into a single or reduced
number of composite measures ("factors"). Through this procedure,
factors that represent the original variable as much as possible, i.e.,
that carry high loadings of these variables may be formed. If the
factors are expected to be independent of one another, orthogonal
rotation is applied to maximize the loadings of the variables. If they
are not expected to be independent of one another, as is the case in
this study, oblique rotation is applied. The four variables in our data
set cannot be reduced to one factor. Two factors remain, with serum Tg
and urinary iodine concentration loading on the first factor and serum
FT4 concentration loading on the second factor. Serum TSH concentration
loaded initially on both factors, but at the end of the study it loaded
primarily on the second factor (Table 4
). Similar results were found when younger and older children (above and
below the median age) were compared. From the communalities and the
percentage of trace, it may be concluded that the factors formed on the
basis of the scores on the four variables at the beginning of the study
show a better " fit" than those at the end of the observation
period. This corresponds with the disappearance of significant
correlations between most variables at the end of the study as shown in
Table 3
.
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Initially, the supplemented and nonsupplemented groups were fully
comparable. After the oral administration of the iodized oil, the mean
urinary iodine concentration in the supplemented group improved
(Fig. 1A
). The difference between the two groups became smaller when 3–4 mo
later the whole population began to have access to iodized salt
alongside noniodized salt, and the mean urinary iodine concentration
improved in the nonsupplemented group. No quantitative data on the use
of the iodized salt were obtained, but at the end of the observation
period the proportion of nonsupplemented children with urinary iodine
concentrations <0.16 µmol/L had decreased from one half
to about one fifth. At the end of the study (12 mo after the baseline
survey; 10 mo after supplementation) the supplemented and the
nonsupplemented groups did not differ in serum TSH and FT4
concentrations or thyroid volume, but differed in serum Tg
concentration and urinary iodine concentration (P < 0.0001; Fig. 1A
–E
). In both the supplemented
and nonsupplemented groups, all indicators except thyroid volume
improved significantly during the study period. Thyroid volume improved
significantly only in the supplemented group. At the end of the study,
supplemented and nonsupplemented groups also differed with respect to
the correlations between serum concentrations of TSH and Tg, i.e., 0.03
(P = 0.774) vs. 0.23 (P = 0.024)
respectively, and between urinary iodine concentration and serum Tg
concentration. i.e., -0.06 (P = 0.571) vs. -0.30
(P = 0.003), respectively (data not shown).
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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, serum Tg
concentrations are raised as a consequence of elevated serum TSH
concentrations; unlike TSH and FT4, however, Tg is not involved in any
feedback regulatory mechanisms. Thus both urinary iodine concentration
and Tg are independent measures of iodine supply to the body.
Unfortunately, there is great interlaboratory variation in the
measurement of serum Tg concentration. At the present time, cut-off
values are based on values obtained in individual laboratories.
Therefore, it will be necessary for methods for estimating serum Tg
concentration to be standardized before they can be applied widely in
monitoring iodine status in programs to control iodine deficiency.
Serum concentrations of TSH, the recommended indicator for use in
screening newborn infants, and of FT4 cannot be regarded as appropriate
indicators for detecting moderate-to-severe iodine deficiency in
children of this age. On the basis of these concentrations, the iodine
status of the study population would have been classified as within the
normal reference range (5
,15
–17)
, both at the beginning
and at the end of the study period. Under the conditions of low iodine
intake as found in our study area, it is plausible to assume that
thyroid hormone production has been affected negatively, causing a
temporary increase in serum TSH concentration. This could induce
initially increased bloodflow through the thyroid and subsequently
hypertrophy and hyperplasia. These mechanisms would result in increased
production of thyroxine (T4). Once T4 production has increased to
satisfactory levels, serum TSH concentrations would fall. This may
explain why mean serum concentrations of FT4 and TSH were found to be
within the normal range. However, changes in serum FT4 and TSH
concentrations after increased iodine intake were still significant.
Moreover, the proportions of children whose serum concentrations of FT4
were too low or whose serum concentrations of TSH were too high were
significantly diminished. This suggests that the normal reference range
of these indicators may be too wide to detect mild-to-moderate degrees
of iodine deficiency, or alternatively, that conclusions with respect
to thyroid function under such conditions may not be drawn on the basis
of results of these two indicators alone.
As suggested by several authors (19
–22)
, the "normal"
concentration of FT4 may also have been the result of a lower
deiodination of T4 because of a concurrent severe selenium deficiency.
In a subsample (n = 23) of our study population, the
mean serum selenium concentration was only 28 ± 12
µg/L, whereas in studies in healthy child populations in
Europe, values were found to range from 60 to >100 µg/L
(22)
. A normal serum concentration of FT4 in turn could
account for the normal serum concentration of TSH.
Although mean serum TSH concentration at baseline was within the normal
range, TSH measurements in whole-blood spots showed that 42% of
the children had concentrations >5 mU/L whole blood.
Although there are doubts about the applicability of the latter
cut-off point in age groups other than neonates (5)
,
this rate may still be considered high and concurs with our data on
goiter rates and urinary iodine concentration, which indicated a
moderate-to-severe public health problem. However, the correlation
between the concentrations of TSH in serum and whole blood, although
significant, was not very high (r = 0.33). Furthermore,
although initial serum TSH concentration was correlated with all other
indicators except thyroid volume, the TSH concentration in blood spots
was correlated only with FT4. Therefore, the validity of the filter
paper method for whole-blood TSH may be questioned.
Comparison of the performance of the various indicators in the
supplemented and nonsupplemented groups 10 mo after supplementation
shows that thyroid volume and serum concentrations of TSH and FT4 were
not significantly different between these two groups. Because the whole
population began to have access to iodized salt 3–4 mo after
supplementation, children in the supplemented group did not maintain
their better iodine status, except with respect to the concentration of
Tg in serum and iodine in urine. It would only be a matter of time for
the nonsupplemented children to catch up fully with the supplemented
children. It is noteworthy, however, that even after both groups had
access to iodized salt for 6 mo, serum Tg concentration and urinary
iodine concentration were still significantly better in the
supplemented group. This further supports our proposition that Tg and
urinary iodine concentration are more sensitive indicators than TSH or
FT4.
Correlations between all indicators of iodine status decreased considerably when iodine status improved. At the end of the follow-up period they were still stronger in the nonsupplemented group than in the supplemented group. When serum indicators of iodine status reach normal values and show less variation, correlations between indicators are likely to disappear.
Over the study period, all indicators except thyroid volume changed
significantly in the study population as a whole. Thyroid volumes were
significantly reduced only in the supplemented group. Earlier studies
showed different rates of reduction of thyroid volume after iodized oil
administration, some showing a rapid response (23
,24)
and
others a more modest or gradual response (2
,25
,26)
.
Reduction in goiter sizes and goiter rates after the introduction of
iodized salt have generally been modest. In a study in Italy
(27)
, iodized salt prophylaxis prevented the development
of goiter in children born after the introduction of the salt, but was
less effective in reducing goiter size in children born earlier. In a
recent study carried out in South Africa (28)
, the
prevalence of goiter was not reduced 1 y after the introduction of
mandatory salt iodization, whereas urinary iodine concentration was
indicative of an improved iodine supply. Similar results were also
reported from Indonesia (29)
. Therefore, thyroid volume is
not appropriate as an indicator for measuring change in iodine status
in the short term.
Current recommendations suggest that thyroid volumes be related to body
surface rather than to age in populations with a high prevalence of
malnutrition because of its effect on growth and development of the
thyroid gland (7)
. This was confirmed in our study, in
which the older tertile was significantly more undernourished (lower
weight-for-age) and stunted (lower height-for-age) than was the younger
tertile, thus providing an explanation why thyroid volume was not
related to age but was related to body surface. The age differences in
degree of malnutrition probably may be ascribed to a period of severe
drought and hunger in the study area in 1987.
The results of this study show that " iodine status," like iron status, is a concept not easily captured in one indicator. It may well be that concomitant selenium deficiency would explain the relatively high serum concentration of FT4 and the relatively low serum concentration of TSH in this iodine-deficient population. In population-based studies, depending on the age of the target group, different combinations of indicators should be used. Under the conditions found in Benin, serum Tg concentration together with urinary iodine concentration are in our opinion the best combination of indicators for schoolchildren aged 7–10 y.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: FT4, free thyroxine; NCHS,
National Center for Health Statistics; T4, thyroxine; Tg,
thyroglobulin; TSH, thyroid-stimulating hormone.
Manuscript received May 1, 2001. Initial review completed May 29, 2001. Revision accepted July 17, 2001.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Buchinger W., Lorenz Wawschinek O., Semlitsch G., Langsteger W., Binter G., Bonelli R. M. & Eber O. (1997) Thyrotropin and thyroglobulin as an index of optimal iodine intake: correlation with iodine excretion of 39,913 euthyroid patients. Thyroid 7:593-597.[Medline]
2. Benmiloud M., Chaouki M. L., Gutekunst R., Teichert H. M., Wood W. G. & Dunn J. T. (1994) Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection. J. Clin. Endocrinol. Metab. 79:20-24.[Abstract]
3.
Pardede L. V., Hardjowasito W., Gross R., Dillon D. H., Totoprajogo O. S., Yosoprawoto M., Waskito L. & Untoro J. (1998) Urinary iodine excretion is the most appropriate outcome indicator for iodine deficiency at field conditions at district level. J. Nutr. 128:1122-1126.
4. Missler U., Gutekunst R. & Wood W. (1994) Thyroglobulin is a more sensitive indicator of iodine deficiency than thyrotropin: development and evaluation of dry blood spot assays for thyrotropin and thyroglobulin in iodine-deficient geographical areas. Eur. J. Clin. Chem. Clin. Biochem. 32:137-143.[Medline]
5. WHO/UNICEF/ICCIDD (1994) Indicators for assessing iodine deficiency disorders and their control through salt iodization 1994 WHO Geneva, Switzerland. .
6. Delange F., Benker G., Caron P., Eber O., Ott W., Peter F., Podoba J., Simescu M., Szybinsky Z., Vertongen F., Vitti P., Wiersinga W. & Zamrazil V. (1997) Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency. Eur. J. Endocrinol. 136:180-187.[Abstract]
7. WHO & ICCIDD (1997) Recommended normative values for thyroid volume in children aged 6–15 years. Bull. WHO 75:95-97.[Medline]
8. Feldt-Rasmussen U., Profilis C., Colinet E., Black E., Bornet E., Bourdoux P., Carayon P., Ericsson U. B., Koutras D. A., Lamas de Leon L., DeNayer P., Pacini F., Palumbo G., Santos A., Schlumberger M., Seidel C., Van Herle A. J. & DeVijlder J.J.M. (1996) Human thyroglobulin reference material (CRM 457). 1st part: assessment of homogeneity, stability and immunoreactivity. Ann. Biol. Clin. 54:337-342.
9. Feldt-Rasmussen U., Profilis C., Colinet E., Black E., Bornet E., Bourdoux P., Carayon P., Ericsson U. B., Koutras D. A., Lamas de Leon L., DeNayer P., Pacini F., Palumbo G., Santos A., Schlumberger M., Seidel C., Van Herle A. J. & DeVijlder J.J.M. (1996) Human thyroglobulin reference material (CRM 457). 2nd part: physicochemical characterization and certification. Ann. Biol. Clin. 54:343-348.
10. Dunn J., Crutchfield H., Gutekunst R. & Dunn A. (1993) Methods of measuring iodine in urine 1993 ICCIDD/UNICEF/WHO Wageningen, The Netherlands. .
11. DuBois D. & DuBois E. F. (1916) A formula to estimate the approximate surface area if height and weight be known. Arch. Intern. Med. 17:863-863.
12. Hair J. F., Anderson R. E., Tatham R. L. & Black W. C. (1998) Multivariate Data Analysis 1998 Prentice-Hall Upper Saddle River, NJ. .
13. Pollitt E. & Metallinos-Katsaras E. (1990) Iron deficiency and behavior: constructs, methods and validity of the findings. Wurtman R. J. Wurtman J. J. eds. Nutrition and the Brain 1990:101-146 Raven Press New York, NY. .
14. World Health Organization (1983) Measuring change in nutritional status—guidelines for assessing the nutritional impact of supplementary feeding programmes for vulnerable groups 1983 WHO Geneva, Switzerland. .
15. Wiedemann G., Jonetz-Mentzel L. & Panse R. (1993) Establishment of reference ranges for thyrotropin, triiodothyronine, thyroxine, and free thyroxine in neonates, infants, children and adolescents. Eur. J. Clin. Chem. Clin. Biochem. 31:277-288.[Medline]
16. Wiersinga W. M. Krenning E. P. eds. Schildklierziekten [Diseases of the thyroid] 2nd ed. 1998 Bohn Stafleu van Loghum Houten, The Netherlands .
17. Nelson J., Clark S., Borut D., Tomei R. & Carlton E. (1993) Age-related changes in serum free thyroxine during childhood and adolescence. J. Pediatr. 123:899-905.[Medline]
18. Dunn J. T. & Dunn A. D. (2000) Thyroglobulin: chemistry, biosynthesis and proteolysis. Braverman L. E. Rutiger R. D. eds. Werner and Ingbar’s The Thyroid. A Fundamental and Clinical Text 8th ed. 2000 Lippincott Williams & Wilkins Philadelphia, PA .
19. Arthur J. (1999) Functional indicators of iodine and selenium status. Proc. Nutr. Soc. 58:507-512.[Medline]
20.
Hotz C., Fitzpatrick D., Trick K. & L’Abbe M. (1997) Dietary iodine and selenium interact to affect thyroid hormone metabolism of rats. J. Nutr. 127:1214-1218.
21.
Vanderpas J. B., Contempre B., Duale N. L., Deckx H., Bebe N., Longombe A. O., Thilly C. H., Diplock A. T. & Dumont J. E. (1993) Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am. J. Clin. Nutr. 57:271S-275S.
22. Zagrodzki P., Szmigiel H., Ratajczak R., Szybinski Z. & Zachwieja Z. (2000) The role of selenium in iodine metabolism in children with goiter. Environ. Health Perspect. 108:67-71.[Medline]
23. Tonglet R., Bourdoux P., Tshilembi Minga & & Ermans A. M. (1992) Efficacy of low oral doses of iodized oil in the control of iodine deficiency in Zaire. N. Engl. J. Med. 326:236-241.[Abstract]
24. Zimmermann M., Adou P., Torresani T., Zeder C. & Hurrell R. (2000) Iron supplementation in goitrous, iron-deficient children improves their response to oral iodized oil. Eur. J. Endocrinol. 142:217-223.[Abstract]
25.
Phillips D.I.W. & Osmond C. (1994) Iodine supplementation with oral or intramuscular iodized oil. A two-year follow-up of a comparative trial. Int. J. Epidemiol. 18:907-910.
26. Elnagar B., Eltom M., Karlsson F., Ermans A., Gebre-Medhin M. & Bourdoux P. (1995) The effects of different doses of oral iodized oil on goiter size, urinary iodine, and thyroid-related hormones. J. Clin. Endocrinol. Metab. 80:891-897.[Abstract]
27.
Aghini Lombardi F., Antonangeli L., Pinchera A., Leoli F., Rago T., Bartolomei A. M. & Vitti P. (1997) Effect of iodized salt on thyroid volume of children living in an area previously characterized by moderate iodine deficiency. J. Clin. Endocrinol. Metab. 82:1136-1139.
28.
Jooste P. L., Weight M. J. & Lombard C. J. (2000) Short-term effectiveness of mandatory iodization of table salt, at an elevated iodine concentration, on the iodine and goiter status of schoolchildren with endemic goiter. Am. J. Clin. Nutr. 71:75-80.
29. Untoro J. (1999) Use of Oral Iodized Oil to Control Iodine Deficiency in Indonesia. Doctoral thesis 1999 Wageningen University Wageningen, The Netherlands. .
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 M. B Zimmermann, D. Moretti, N. Chaouki, and T. Torresani Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1453 - 1458. [Abstract] [Full Text] [PDF]
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