FREE FULL TEXT

Iodine and selenium deficiency associated
with cretinism in northern Zaire13
Jean B Vanderpas,
Kibambe
Niambue,
ABSTRACT
Selenium
demic-goiter
the
area
reference
nium
Bernard
Jacques
and
values
in subjects
Contempr#{233}, Ngidai
L Duale,
Willy Goossens,
Ngo
Dumont,
Claude
H Thilly,
and Anthony
T Diplock
status
was
in a control
determined
area
in the core
area,
ofthe
northern
(RBC-GPX)
still two
times
iodine-deficient
status
was
lower
city
was
five
of the
moderately
At Karawa
normalized
both
the
endemia
‘
moderate
In a less severely
(Businga),
selenium
linearly
WORDS
Iodine
and
Subjects
the
deficiency,
RBC-GPX.
selenium
The
goiter
This
deficiency,
cre-
Introduction
Since
the description
layan
valleys,
guished.
overt
with
of McCarrison
two
forms
Endemic
disease
retardation
frequently
and
normal
growth,
deficiency.
Nepalese
Hima-
classically
distin-
is characterized
and
variable
with
function.
deaf-mutism,
More
than
tral
(8), whereas
Africa.
Northern
4 million
Zaire
people
6% cretinism
form
[78-85%
and
is covered
of the
cretinism
rate
cretins
goiter
(9),
mostly
of cases
Am J C/in Nuir
l990;52:
deficiency
1087-93.
of the
in Cenbelt
rate
affecting
and
at a 2-
myxedematous
( 10, 1 1 )].
for a variable
distribution
unclear.
It was recently
selenium
is uncommon
prevalence
could
Printed
ofboth
proposed
involve
in USA.
forms of cretinthat a combined
the
(Kikwit).
the
of the
deficiency
The
same
in Karawa
and
and
in a Zairian
selenium
villages
selenium
endemic-goiter
status
was
area
in normal
also
compared.
Karawa
along
same
endemia.
9-18
y) and
in two
rural
2 (Botolo)]
Zaire
the
and
in a small
Ubangi
River
In the first two
28 cretins
villages
close
to Karawa
ofthe
endemic-
in the core
(aged
town
(Businga)
villages,
3-25
was obtained
according
teachers,
both parents,
were
language
in local
sex-paired
subjects
samples
were
obtained
during
blood
collections
verbal
consent.
In these
of the
from
for
Height
median
same
area.
30 hospitalized
medical
places
iodized
Medical
Team,
Public
In-
custom.
children
community
health
was recorded
and exheight
of normal
ageAt Businga
adults
checkups
three
examined.
to local
and the
by the local
of the nature
of the study.)
as the percentage
of the
at 90
at the border
52 schoolchildren
y) were
formed
verbal
consent
(The village
chief,
the
informed
located
biological
(21-42
after
oil has been
years)
informed
available
thyroid
© 1990 American
From
the Cemubac
Health
School.
Free Uni-
versity of Brussels;
Communaut#{233} Evang#{233}lique de l’Ubangi-Mongala,
Karawa, ZaIre; Laboratorium
van Hematologie,
Gasthuisbergziekenhuis,
Leuven, Belgium; Ecole de Sante Publique,
Kinshasa,
ZaIre; Bureau des
Troubles
dus a la Carence
Iod#{233}e,
Kinshasa,
ZaIre; Institut de Recherche
Interdisciplinaire
en Biologie Humaine
et Nucl#{233}aire,Campus
Erasme,
Free University
ofBrussels;
and Division ofBiochemistry,
United Medical
and Dental Schools, University
of London.
Guy’s Hospital,
London.
2 Supported
in part by the Centre d’Etudes
M#{233}dicaleset Scientifiques
de l’Universit#{233}de Bruxelles pour les Actions de Cooperation
(Cemubac);
the Academic
Programs
and Medicine
Overseas (APMO),
Brussels University; the Fonds de Ia Recherche
Scientifique
M#{233}dicale
(contract
FRSMULB 3.4507.87),
Belgium;
and the Wellcome
Trust, London.
3 Address
reprint requests to I Vanderpas.
Clinique
Louis Caty, 7420
Baudour,
Belgium.
Received
October
6. 1989.
Accepted
for publication
January
24. 1990.
normal
50%
by an endemic-goiter
at a 65-85%
prevalence
The reason
ism remains
iodine
neurological
iodine
of the
and
of northern
(aged
I
of cretinism
are neurological
in Papua
New Guinea
(2), Latin
America
(3, 4), Vietnam
(5), eastern
China
(6), Algeria
(7), and
Sicily
in myx-
by
intellectual
cretins
show a severe
neuand ataxic gait) and mental
associated
thyroid
are
cretinism
stunted
development.
Endemic
neurological
rological
impairment
(spastic
diplegia
growth,
iodine
(1) in the
of this
myxedematous
hypothyroidism,
severe
oflife
to determine
core
in Businga)
was conducted
ofthe
and
is associated
years
methods
1 (Boyalulia)
area
leader
pressed
cretinism
study
km from
tinism
Endemic
(severe
goiter
was
in the
deficiency
in cretins
and
[villages
combined
iodine
and selenium
deficiency
could
be associated
with the elevated
frequency
ofendemic
myxedematous
cretinism
in Central
Africa.
Am J Clin Nutr
1990;52:l087-93.
KEY
endemic
subjects
first
selenium
was
supplementation
and
work
living
Zaire
the
(14).
present
iodine
without
concentration
up to a value of
15 U/g Hb at greater
selenium
selenium
of the
Thorpe,
during
of Zaire
in a population
belt of northern
in 52 schoolglutathione
activity
aim
status
13) observed
cretins
The
sele-
endemic-
in schoolchildren
0.004).
RBC-GPX
villages,
serum
lower
=
(P
same
altered.
associated
with serum
selenium
1 140 nmol/L
and leveled
offat
concentration.
times
in cretins
(12,
edematous
Roger
in-
Society
for Clinical
Nutrition
1087
Downloaded from www.ajcn.org by on August 6, 2009
and
volution
enwith
serum
Zaire
goiter belt (Karawa
villages)
was seven times lower
children
and similarly
low in 23 cretins;
erythrocyte
peroxidase
an
Compared
of a noniodine-deficient
living
in
ofZaire.
Bebe,
1088
VANDERPAS
to pregnant
Nine
women
medical
attending
and
the
paramedical
prenatal
workers
iodine-deficient
area
(Kikwit,
Bandundu
control
The
protocol
was approved
subjects.
ofthe
hospitals
ofKarawa
and
of the Ecole de Sante
Publique
committee
of the
Erasme
region)
A).
and
The
University
2 mo with
were
[50 g
International,
B) or with
schoolchildren
placebo
the
Se/d
the next 4 mo into
as selenomethionine)
as
2 (group
of each
a supplemented
and a placebo
was
of
sumed/2
wk).
before
Selenium
the end
that
the
results
children
study
because
function,
12 tablets
interrupted
oflogistical
tablets.
iodized
oil [0.5
period
group.
were
chi-square
17 d
linear
France)]
was adto all school-
in tubes
for erythrocyte
treated
determination
with
enzyme
ethylenediamine
of hematological
surement
of erythrocyte
tubes
for measurement
lenium
concentration.
with
adenine
citrate
activity
indices
and
for
mea-
thyroid
status
the
was
serum
and
at Baudour,
free
VILLAGE
thyroxine
Belgium,
I
Day6O113N+1Or1
I
I
I
1
I
6
I
obtained
was
subdividing
performed
by
the
by a model
of
analysis
was per-
the independent
of subjects
in the
variables
three
analysis.
The multifactorial
of the endemic
area who
the
All
Statistical
by one-
in the same
variance
of the
statistical
groups)
analysis
were relabiological
procedures
Package
for
Social
were
Sciences
mc, Chicago).
I shows
in the
subjects
high
at Kikwit
+
of Businga
(4.53
P
<
epidemiological
and
and
Kikwit.
mol/L)
0.001);
cretins
and
it was
trend.
the
adult
Compared
patients
with
and
of Karawa
Mean
urinary
moderately
extremely
in schoolchildren
(0.20
mol/L)
The indices
ofthyroid
function
graphical
N
the baseline
schoolchildren
mol/L;
similar
mol/L).
Kikwit,
[
f13N+7crJ
of means
and
calculated
after
the
SPSS,
comparison
were
com-
Belgium.
and in the
and urinary
mean
(geo-
(ANOVA)
was
concerning
with
The
measures
(homoscedasticity).
adult
VILLAGE
1100 ug Se]
i-I
Month
homogeneous
(0.38
total
I
TI ___________
tables.
number
with
Serum
TSH
as geometric
+ b). Multifactorial
by multiple-regression
limited
to the subjects
Table
by
(T4 , FL1),
26N+17’l
DayO
measured
FRG)
in Leuven,
± 1 SD in the text
= ax
and
was
values
plasma,
and sera were kept
which were performed
within
determined
total
were
of frequencies
same
elim-
Glucose-6-phosphate
Results
1 mo.
The
(ie,
(SPSSPC+,
at -4 #{176}C
until their arrival
at Brussels
enzyme
activity
was determined
on
the same
day. Erythrocyte
lysate,
frozen
for the other measurements,
measuring
by ANOVA
gluta-
after
to Beutler
acid-
selenium
concentration,
and in plain
of serum
thyroid
indices
and serum
seAll samples
were immediately
stored
in
box and kept
h. Erythrocyte
(y
(15).
and
(16).
of variance
regression
tertiles
conducted
mea-
tetraacetic
The
into
tively
and
repeated
comparison
regression
formed
Lipiodol
kinase
Mannheim,
as means
in text
when
test.
variables
collected
pyruvate
by analysis
The
con-
to the
mL
i ± 1 SD)
performed
way ANOVA
difficulties
According
and
platelets
and as i ± 1 SEM in the figures.
concentrations
are expressed
metric
cretins.
in tubes
a refrigerated
within
48
(
and
fractions
CA). Se-
(RBC-GPX)
according
as
deter-
in London
peroxidase
measured
of leukocytes
tables
iodide
(group
plus 4
The compliance
every
2 wk and
was
of selenium
as anticoagulant
surement,
for
to the
samples
dextrose
all subjects
time (Guerbet,
Aulnay-sous-Bois,
at the end of the 2-mo
study
and
Blood
6-mo
supply
ofthyroid
per os one
ministered
for
were
measured
S were
the various
Fullerton,
by spectrofluorimetry
mercial
kits (Boehringer,
Values
are expressed
was
supplementation
ofthe
impeded
initial
K3
sufficient
was
A, A2 , and
the
of Businga
low
low
normal
were
values
euthyroid
9 Crj
I
14N+4rj
I
I
I
tPIacebol
I
FIG I . Study design of the selenium
supplementation
(Se) or placebo
normal schoolchildren
(N) and in cretins (Cr) oftwo villages of Karawa.
2 (groups
A-F) are also indicated.
was
at Businga
at Karawa
IPlacebo
J1ooiigse
in the
iodide
and
and in cretins
(0.16
followed
the same geo-
II
I
biological
and
administration
(one tablet per day per os) in
The corresponding
groups described
in Table
observed
but
in
an
Downloaded from www.ajcn.org by on August 6, 2009
considered
concentration
Hemoglobin
glutathione
dehydrogenase
for
mo
it was
measured
reductase
ination
(100 zg Se po/d
[village
1, 6 mo
2 wk.
tablets
was
Erythrocyte
1
group
(group
D) and 2 mo selenium
plus 4 mo placebo
E); village 2, 6 mo placebo
(group
F) and 2 mo placebo
iodide
(14).
lenium
in village
selenium
selenium
(group
C)].
Each child
received
1 5 tablets
every
was verified
by counting
the remaining
Urinary
reported
(group
thione
globby radioimT4, FF4, T3,
Corp, Los Angeles;
TBG, Behring,
Diagnostic,
Chavannes-de-Bogis,
mined
by electrophoresis
on agarose,
and
were calculated
by densitometry
(Beckman,
subdivided
subgroup
subgroup
thyroxine-binding
serum
for
B’). The
village
Diagnostic
Product
FRG;
rT3 , Serono
Switzerland).
as selenomethionine
UK)]
(T3 , ri’3),
and thyrotropin
(TSH)
concentrations
in duplicate
with commercial
kits (for
and TSH,
Marburg,
in the two
supplemented
Surrey,
triiodothyronine
previously
in all the subjects
per os (po)
reverse
ulin (TBG),
munoassay
Brussels.
were
AL
and
staff
supplementation,
cretins
in village
cretins
volunteered
was organized
Leatherhead,
and
1984.
in a non-
by the medical
Hospital,
measured
and
selenium
(Wassen
(group
RBC-GPX
schoolchildren
since
Kikwit,
by the medical
authorities
of Kinshasa,
and by the ethical
A trial ofselenium
supplementation
villages
close to Karawa
(Fig 1). Before
selenium
clinics
of a hospital
ET
IODINE
TABLE
1
Baseline
values
of subjects
living
in the northern
Zaire
AND
goiter
SELENIUM
belt (Karawa,
Group A, Karawa
Normal
children
Age (y)
13.8
2.1tCD
±
Sex ratio, M/F
G6PD
1 U/g Hb
<
RBC GSH-reductase
(U/g Hb)
RBC pyruvate kinase (U/g Hb)
Hemoglobin
A2 3.5% (n)
>
Hemoglobin
S
20% (n)
>
ofsubjects,
I
±
RBC, red blood cell; G6PD,
1 SD, or geometric
mean
glucose-6-phosphate
with range
proportion
schoolchildren
roidism
and
severe
ofgoiter
presented
the cretins
hypothyroidism.
enzyme
drogenase,
dehydrogenase
hemoglobin
(hemoglobin
moglobin
A2 consistent
four
selenium
and
markedly
lower
± 355
ofKikwit
in both
(n
= 29),
nmol/L
[343
(n
than
P
<
(n
concentration
=
was
also
children
[red
measured.
[304
± 176
0.001]
similar
blood
RBC
(<
nmol/L
0.1]
patients
P
of Businga
in volunteers
In Karawa
0.001].
<
twice
(1 ± 1
and was
as low in cretins
<
cell,
I 140
control
(RBC)]
It was similarly
(n
RBC
= 12)]
deficient
areas.
The relationship
between
lenium
and of RBC-GPX
range
in school-
>
or than
= 9),
almost
Belgian
± 1 33 nmol/L
± 156 nmol/L
nium
were
<
2.2 U/g
to that of 20 adult
Hb).
Erythrocyte
was
of he-
[ 1.7 ± 1 .8 U/g Hb (n = 27) vs 3.3 ± 2.4 U/
= 0.004] and was markedly lower than at
U/g Hb (n = 25), P
0.001]
or at Kikwit
Hb (n = 8), P
0.00 1]. This last value
was
as in schoolchildren
U/g
dehyof glu-
similar
= 23), P
in adult
subjects
(1 5.0
selenium
extremely
(n
= 27)]
of Karawa
Group C, Businga
Adult patients
[28]
± 2.8
concentration
low
and
compared
(by ANOVA
nmol/L),
the
relationship
34.0
± 10.6 [9]
2/7AjB
Not done
0/OtABC
[9]
99.9 ± 34.1 [9]
21.8 ± 2.2jAB
[9]
12.8 ± 2.9 [9]
1.82 ± 0.41 [9]
270 ± 42 [9]
2 (l-4)tAB
[9]
4.53 (0.65-31.36)
[9]
5.92 ± 0.94 [7]
2 [9]
4.52 ± 2.00 [8]
10.75 ± 3.39 [8]
5 [9]
2 [9]
±
TSH and urine
variables
iodide);
normal
in school-
the
total number
ofcases
in brackets.
Multifactorial
was
limited
was
P
curve
well.
§
0.05,
<
P
0.01.
<
At greater
were
selenium
leveling
off at a
regression.
not
The
is known
a significant
Table
to affect
effect
RBC-GPX
(data
did
After
interruption
of selenium
of the
(see
trations
with
non-
after
6 mo.
and
thereafter
the
C) and
of serum
multiple
multifactorial
indices
(17),
analysis,
did not disclose
the
of the
selenium
of selenium
effect
of iodine
or
and
subjects
for 4 mo
6 mo
serum
(group
between
reached
similar
in the
RBC-GPX
accidental
selenium
the
a normal
placebo
(group
to those
observed
supple-
before
mean
for 2 mo
end
concen-
D) of selenium
those
and
those
RBC-GPX
By contrast,
supplemented
with
status
supplementation
17 d before
mean
supplementation.
to increase
concentrations
effect
or in the
was normal
whereas
value. As a result ofthe
intermediate
The
in a mul-
of RBC-GPX
The
supplementation
2 mo ofselenium
after
0.05);
<
modify
2 mo
Methods),
at 4 (group
were
not
the evolution
B), serum
selenium
about halfthe
normal
study
TSH.
in the
A
was
not shown).
of Karawa.
(group
reached
(P
ANOVA
the thyroid
and
3 shows
subjects
of age
effect
by ANOVA
effect
and
in the
to ensure
regression.
determined
T4, VF4,
addition
area
the main
multiple
TSH
and
supplementa-
endemic
and
for serum
significant
of iodine
As expected,
a supplementary
for serum
was
which
only
effect
selenium
of the
ofRBC-GPX
analysis
observed
selenium
subjects
in ANOVA
significant
tiple-regression
2) of the
(before
ofvariance.
effect
statistically
(Table
observed
supplementary
GPX
0.001,
hormones
to the
of iodine
mentation
both
<
of RBC-GPX
analysis
homogeneity
[279
values
of serum
se3. In the low-sele-
values
on thyroid
a relative
was
P
value.
selenium
tion)
test): t
fit a linear-regression
concentrations,
in cretins
between
Group D, Kikwit
Adult control subjects
4.5D
[30]
lO/2OtAfB
Not done
7/4tA [30]
99.9 ± 41.7 [30]
22.3 ± 2.9AtB
[30]
14.4 ± 4.1 [30]
1.51 ± 0.62A
[30]
197 ± 150 [30]
1 (0.4-4)tAB
[30]
0.37 (0.18-0.78)tD
[17]
Not done
Not done
4.86 ± 1.41 [25]
Not done
8 [30]
4 [30]
or chi-square
continued
the individual
is given in Figure
29.0
(for serum
erythrocyte
of abnormal
trait)
2) was
g Hb (n
46), P
Businga
(8.7 ± 4.7
±
normal
concentrations
(Fig
groups
± 347
nmol/L
[2555
RBC-GPX
[1 5.0
similar
and
a fl-thalassemia
in cretins
of Karawa
± 188 nmol/L
= 52) vs 443
the
the mean
increased
concentration
SD n
[753
the
groups.
Serum
children
with
letter(s)
glucose-6-phosphate
and the prevalence
deficiency
S and
in parentheses
of juvenile
hypothysigns of extremely
hand,
kinase,
reductase)
9.5tCD
area (Kikwit)5
GSH, glutathione.
by capital
In Karawa
pattern
biological
On the other
activity
(pyruvate
and glutathione
cose-6-phosphate
in the
was present.
a clear
showed
noniodine-deficient
B, Karawa
Cretins
28 [28]
9/3tA [28]
10.8 ± 8.1tACD
[25]
30.3 ± 4.2 [20]
0.79 ± 1.31tACD
[25]
0.91 ± 0.6OtACD
[25]
3 ± 1tACD
[20]
246 (l05-578)CtD
[25]
0.16 (0.07-0.35)CtD
[24]
6.51 ± 1.61 [23]
2 [25]
5.10 ± 1.89 [25]
9.88 ± 3.14 [25]
2 [25]
7 [25]
dehydrogenase;
t Significantly
lower than the group(s) indicated
II A calculated
for subjects not deficient
in G6PD.
elevated
and in a Zairian
concentration
with
E) presented
at 2 mo,
selenium
RBCwhereas
Downloaded from www.ajcn.org by on August 6, 2009
Number
S
±
1089
17/1 1
26tB [53]
41/12 [53]
66.3 ± 39.3tCD
[53]
25.8 ± 4.8B [53]
8.86 ± 5.59tCjJ)
[53]
1.94 ± 0.51 [53]
1 19 ± 99tCD
[51]
10 (2-69)tB
[53]
0.20 (0.09-0.464CtD
[48]
6.49 ± 1.33 [51]
I [52]
4.51 ± 1.13 [52]
10.08 ± 2.52 [52]
4 [52]
6 [52]
(U/g hgb)
RBC G6PD
13.1
41/12
Stature < local median
Goiter, total/visible
Serum 1’4 (nmol/L)
Serum TBG (mg/L)
Serum VF4 (pmol/L)
Serum T3 (nmol/L)
Serum rT3 (pmol/L)
Serum TSH (mUlL)
Urine iodide (zmol/L)
RBC
Businga)
Group
[53]
DEFICIENCY
VANDERPAS
1090
RBC-GPX
(U/g
ET
AL
20.0
21
hgb)
16.0
12.0
8.0
4.0
<0.2
SERUM
SELEMUM
3000
2500
nmoIII)
2000
1500
1200
< 0.2
800
nmol/I
.:;!:.
400
KARAWA
SCHOOLCHILDREN
BUSINGA
ADULT PATiENTS
KARAWA
CRETINS
KIKWIT
ADULT CONTROLS
FIG 2. Comparison
of individual
values and mean concentrations
SEM) of erythrocyte
glutathione
peroxidase
(RBC-GPX)
and of
serum
selenium
in normal
schoolchildren
and in cretins of Karawa,
northern
Zaire (severe iodine deficiency),
in adult hospitalized
patients
of Businga,
northern
Zaire (moderate
iodine deficiency),
and in adult
normal volunteers
ofa noniodine-deficient
area (Kikwit, Central Zaire).
(±1
serum
selenium
had decreased
than before
supplementation.
After 2 mo ofselenium
increase
nounced
than
and
6-mo
cebo
= 24),
was
selenium
group
2 mo,
= 8)].
Hb(n
± 285
the evolution
similar
in cretins
RBC-GPX
selenium
and at 6 mo,
3.0 ± 2.7 U/g
= 9)
n
greater
selenium
was
more
nmol/L
(n
ofserum
and
were
at 2 mo,
= 23),
301 ± 1 1 1 nmol/L
Hb (n
27), and
=
in schoolchildren.
in the
pla-
nmol/L
(n
(n
6); RBC-GPX
at 6 mo, 3.5 ± 3.3
at
U/g
479
± 233
=
=
an osteoarthropathy
pro-
selenium
not modified
FIG 3. Relationship
of RBC-GPY
and serum selenium
in normal
schoolchildren
and cretins of Karawa, northern
Zaire (crosses and open
circles), in adult hospitalized
patients ofBusinga,
northern
Zaire (closed
triangles), and in adult volunteers
ofKikwit,
central Zaire(open
triangles).
The analyses
were performed
before selenium
supplementation.
The
hatched area represents
the range of values in European
countries.
The
equation
of the linear regression
for the selenium
values < 1000 nmol/
L is y - 0.O2lx - 4.8 (r
0.63; P < 0.001); for the selenium
values
>
1000 nmol/L,
the coefficient
ofthe slope was not statistically
different
from zero and it was considered
that the linear regression
could fit the
equation
y = constant
(r = 0.05; P > 0.5).
Selenium
deficiency
has been
endemic
diseases,
a cardiomyopathy
=
and
[serum
the serum
nmol/L,
[944
supplementation,
RBC-GPX
Serum
barely
was true for RBC-GPX
[10.33
± 5.31 U/
± 2.19 U/g Hb (n
24), P < 0.05].
After
P
4- and
± 547
in schoolchildren
= 0.002]; the same
g Hb (n = 9) vs 5.76
to values
supplementation,
( 1 724
in cretins
markedly
SELENIUM
lenium
in these
called
affected
associated
called
Kashin-Beck
populations
in China
with
Keshan
disease
disease
was
still
two
and
(19).
Serum
se-
lower
than
the
TABLE
2
Multifactorial
analysis of the effect of iodine (urinary
iodide) and of
selenium
status [serum selenium
and red blood cell glutathione
peroxidase
(RBC-GPX)]
on thyroid indices by ANOVA
and multipleregression
analysis5
Dependent
Analysis
of variance:
values)
Urinary
iodide
RBC-GPX
Serum
selenium
variable
main
Serum
T4
Serum
FT4
Serum
T3
Serum
TSH
13.5t
12.4t
1.4
8.it
1.6
2.7
1.2
4.6
1.3
1.9
0.4
1.9
0.42t
0.5 It
0.07
0.09
1.5
-0.58t
0.67t
29t
effects
(F
Discussion
These
data
clearly
in the
core
mean
concentrations
times
lower
of the
China
northern
a very
Zaire
goiter
selenium
selenium
belt.
deficiency
At
Karawa
the
three
to seven
lower than in nondeficient
areas (1 8). They
than in New Zealand
(mean
serum
selenium
were
definitely
600 nmol/
barely
of serum
severe
were
L), considered
were
document
to be marginally
greater
considered
than
the
to be severely
selenium
values
observed
selenium
‘
deficient,
and
in some
deficient
(18).
areas
Multiple-regression
r of iodine
analysis
Multiple
r of iodine + RBC-GPX
F value (multiple
r vs r)
they
of
S The
effect of age and serum
ANOVA
or in the multiple-regression
t
P
<
tP<0.05.
0.001.
0.48t
i4t
selenium
was
analysis.
0.59t
24t
not significant
(P
>
0.3)
in the
Downloaded from www.ajcn.org by on August 6, 2009
.::.
SERUM
IODINE
TABLE 3
Evolution
of selenium
status
before
AND
and after selenium
SELENIUM
1091
DEFICIENCY
supplementation5
Serum
selenium
RBC-GPX
nmo//L
A: before selenium
B: 2 mo selenium
C: 2 mo placebo
supplementation
4 mo selenium
+
374
1 163
777
±
839
±
542
±
D: 6 mo selenium
E: 2 mo selenium
1
5
SD. Ratio
±
tf
of the number
Significantly
value
ofthe
studied,
GPX,
lower
subjects
even
4 mo placebo
+
than
of normal
the group
with
undetectable
were in good
health;
of RBC-
in the absence
of specific
in tropical
areas,
cases of Keshan
disease.
The public
health
benefit
ognized
in the extreme
By contrast,
the
uncertain
and
these
tation
corrects
tween
the
activity
different
for
the
serum
selenium
30 d for
the
4 mo
In the
after
stopping
present
deficient
(Businga)
area
and
by serum
status.
as one
severity
selenium
hospitalized
reflect
patients,
bias,
we
the selenium
of age on
negligible,
and
believe
normal.
populations
foods,
whatever
on cassava
and
content
ofthese
live
Metabolic
an interaction
function?
goiter
(Karawa),
assessed
deficiency
subjects
of these
volunteers).
Despite
measured
of the
general
population.
exclusively
studied
(3-42
populations
on
The
this
locally
staple
ev-
y) is
(21).
produced
the socioeconomic
level.
maize
in the three
products
is directly
places
studied.
The selenium
dependent
on the geograph-
food
is based
status
has
[Guatemala
without
investigations
element
Africa?
deficiencies
2) Does
areas
cretinism
(QinghaI
is more
it
status
described
Zealand
and
deficient
(19),
high
(23,
24).
population
was
the
to oxidize
of thyroid
peroxide
detoxifying
described
on
here
issue,
apical
enzyme
(12).
is one
more
argument
function
deiodinases
converting
could
showed
the
plementary
iodine
The
interact
main
effect
is
that
hydrogen
per-
cells
is nec-
and
lead
The
in the forof an excess of
a lack
of hydrogen
to a progressive
geographical
in favor
dele-
association
ofthis
and selenium
deficiency
function);
it does not
hypothesis
causes
constitute
an
a
have clearly
established
interactions
hormones.
The effect of selenium
could
be mediated
T4 into
precise
with
postulated.
analysis
effects
deficiency
of thyroid
gland
would
gland
the thyroid
ciency
io-
(Velingara,
=
it is known
the
proof.
Animal
experiments
of selenium
with thyroid
(32).
and
membrane
in a stimulated
combined
iodine
loss of thyroid
tissues
nutritional
20) (AT Diplock
1988). In summary,
tyrosyl
residues
of thyroglobulin
hormones
(3 1 ). The synthesis
peroxide
effect
(n
previous
in another
to be normal
of selenium
second
at the
hydrogen
Clinical
and
rule.
the
generated
malnutrition
and Sudan
good
whole blood
observations,
association
not
study
concentration
found
se-
Interestingly,
province
than
(28),
relatively
Selenium
iodinewith
deficiency.
present
their
(30).
The
Shanxi
provinces),
Low selenium
iodine
in the
are
the iodine
part
(25).
in this
in
Finland
and
for a small
province)
frequent
of associated
children
on
previously
New
only
acting
on selenium
the
(Guizou,
Heilongjiang,
and
cretinism
is predominant.
status
dine-deficient
terious
elements
data
is rather
overlap
trace
Besides
(13),
demonstrated
proteocaloric
respective
association
of two trace
1) Is it specific
to Central
±
selenium
evidence
Businga
The geographical
raises two issues:
Zaire
of the
than initially
Multifactorial
apart).
±
[46/26]
also been
reported
in proteoenergetic
(26), Eastern
Zaire (27), Jamaica
ical nature
of the soil (22). Great
variations
in selenium
status
were observed
in places
that are close together
(eg, Karawa
and
are 90 km
±
the
of China
lenium-deficient
myxedematous
(ie, that
irreversible
effect
two
question,
countries
areas
essary
mation
accurately
The
in these
Concerning
three
the
are scarce.
or marginally
deficient
oxide
the range of age and the
living
in rural villages,
variables
first
in eastern
certainly
either
3.84tCD
[24/9]
4.29 [10/2]
6.44 [9/10]
5.36CtD
[7/5]
0.05.
<
areas
a geographical
area
there
2.3OtBCDE
±
between
the
endemic-goiter
P
Senegal,
1 1 16 ± 1 56 nmol/L
and JN Lazarus,
unpublished
a noniodine-
the
almost
of
(18).
from
the selenium
status
in the range
at least in nonselenium-deficient
These
by the
(1 d
selenium
conof RBC-GPX
deficiency,
The
hospital
that
status
imply
thyroid
(29)]
§
0.01,
<
examination
6 mo
supplementation
ofselenium
or RBC-GPX.
After
release
their
the stability
places
were heterogeneous
concerning
life conditions
(schoolchildren,
cretins
ident
(18).
progressed
be-
of RBC-GPX
explained
of selenium
was entirely
tissues
explain
selenium
study,
is best
pools
two
be-
discrepancy
that
P
in eastern
China
where
neurological
supplemen-
The
and
(Kikwit)
to an intermediate-severity
to a severe
iodine-deficient
area
was a progressive
is
remains
is intermediate
RBC-GPX)
RBC-GPX
studies
have shown
that some
tent very slowly;
this can also
during
deficiency
selenium
selenium
of supplementation
half-lives
of the
supplementation,
(19).
in humans
As expected,
of serum
selenium,
is rec-
ofChina
the selenium
of the deficiency
altered
after 2 mo
metabolic
conditions
where
situations.
evolution
f
0.001,
moderately
(20).
the severity
two
misdiagnosed
supplementation
of supplementation
controversial
At Karawa
tween
<
supply
Zealand,
benefit
actually
ofselenium
environmental
in New
moderate,
were
±
7.00
1 1.02
13.61
7.61
in brackets.
P
Concerning
that
fre-
2.76
of iodine
by a modulation
T3 and
into
mechanism
thyroid
(ANOVA,
and
rT3 in extrathyroidal
by
function
which
may
multiple
selenium
on
of the
selenium
be more
regression)
on
thyroid
deficomplex
of the
function
effect of iodine
on T4, fT,
and TSH.
A supof RBC-GPX
was seen by multiple
regression
Downloaded from www.ajcn.org by on August 6, 2009
observed
t
( 1 8). All children
clinical
criteria,
it is not possible
to rule out the possibility
some cases of cardiomyopathy
in northern
Zaire,
a disease
quently
±
ANOVA):
concentrations
nevertheless,
185tBCD
[52/23]
512 [23/9]
174tB [10/3]
28ltB
[9/9]
279tBjDE
[7/5]
±
and of cretins
(one-way
( 1 52 nmol/L)
of Karawa
those
schoolchildren
indicated
U/g Hb
1092
for
VANDERPAS
the
same
thyroid
indices
multiple-regression
whereas
the
in the
present
could
explain
powerful
tion.
ANOVA
treats
analysis).
that
test
further
the
graphical
on
in the
province
speculated
This
seems
dehydrogenase
anemia
trait
Kivu
China
(25),
The
may
geo-
deficiency
Lake)
in
(13),
and
the
first
represent
deficiency
function
genetic
diseases
exert an
in at least
known
not
because
to be as-
Nitiyanant
more
frequent
trait,
in cretins.
was twice
serum
could
The
RBC-
concentrations.
genetically
in cretins
sickle
as low as in school-
selenium
is determined
(33)
be a marker
after selenium
supplementation,
to normal
in cretins,
rendering
9.
10.
and
RBC-
and
a lower
of this
disease;
enzymatic
this hypothesis
activity
was
unlikely.
1 1.
12.
It is more
likely that the lower
RBC-GPX
reflected
a lower selenium
supply
in cretins;
RBC-GPX
is a better indicator
of longterm
selenium
data
it is not
cretins
supply
possible
should
foods
than
be lower;
of handicapped
hypothyroidism
is serum
selenium.
to determine
small
why
differences
children
could
in six subjects
ofa
From
the
core
reinforces
edematous
selenium
of the
the
endemic-goiter
hypothesis
cretinism.
be an explanation.
Severe
of
supplementation
in
and
this
coun-
activity
with
public
area
(1
14.
in
15.
Zaire,
which
endemic
myx-
health
remains
benefit
to
be
13.
= 17.8
was documented
northern
of an association
clinical
in
to some
nonselenium-deficient
belt
The
supply
in accessibility
try (Belgium)
did not modify
the RBC-GPX
± 2.3 U/g Hb).
In conclusion,
severe selenium
deficiency
the
the present
selenium
of
16.
N
17.
deter-
mined.
We greatly appreciate
the participation
of Ignace Ronse and Anne
Slimbroek,
Businga
Hospital,
and of Ren#{233}
Snacken,
Kikwit Hospital,
Zaire, and the skilled technical
assistance
in London
of Sue Peach, in
Leuven ofleanine
Lauwers, and in Baudour
ofRaymond
Pawlak, JeanPierre Hut, and Jacques Lalinne. The selenium
supplement
and placebo
tablets were generously
provided
by R Matthews,
Wassen International,
Leatherhead,
Surrey, UK.
18.
19.
cretinism.
demic
Wiley,
3.
DeLong
In: Stanbury
cretinism.
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lB.
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BS, eds.
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Endemic
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New
and
en-
York:
1980:395-421.
GR,
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JB,
Fierro-Benitez
R. Neurological
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be considered
and selenium
on the thyroid
The
data
in classes
analysis
function
iodine
effect
TSH.
individual
in statistical
should
thyroid
of QinghaI,
some subjects.
It was also
phate
for
the
of RBC-GPX
data
Zaire
combined
deleterious
cretinism.
grouped
of cretinism
in eastern
clues that
irreversible
data
difference
is required
association
study,
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all
an effect
these
status
by
treats
multiple-regression
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of selenium
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the
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