Intra-individual variability in TSH levels of healthy women during the first half of pregnancy

Endoc inol
Diabe es
Nu .
2017;64(6):288---294
www.else ie .es/endo
Endoc inología,
Diabe es
y
Nu ición
ORIGINAL
ARTICLE
In a-indi idual
a iabili y
in
TSH
le els
o
heal hy
women
du ing
he
fi s
hal
o
p egnancy
May e
Mu illo-Llo en ea,
Ca men
Faja do-Mon a˜
nanab,∗,
Ma celino
Pé ez-Be mejoa,
Ra ael
Vila-Candela,c,
José
Gómez-Velab,
Inés
Velascod
aDepa men
o
Nu sing,
Ca holic
Uni e si y
o
Valencia
San
Vicen e
Má i .,
C/Espa e o,
7,
Valencia
46007,
Spain
bEndoc inology
Depa men ,
Uni e si y
Hospi al
la
Ribe a,
C a.
Co be a
km
1,
46600
Alzi a,
Valencia,
Spain
cDepa men
o
Obs e ics
and
Gynecology,
Uni e si y
Hospi al
la
Ribe a,
C a.
Co be a
km
1,
46600
Alzi a,
Valencia,
Spain
dPedia ics,
Obs e ics
and
Gynecology
Uni ,
Hospi al
de
Rio in o,
Andalusian
Heal h
Se ice,
A da
La
Esquila
5,
21660
Minas
de
Rio in o,
Huel a,
Spain
Recei ed
4
Janua y
2017;
accep ed
3
Ap il
2017
A ailable
online
20
May
2017
KEYWORDS
TSH;
Cu -o
le el;
Fi s
imes e
Abs ac
Objec i e:
TSH
is
he
pa ame e
mos
widely
accep ed
o
assess
hy oid
unc ion,
especially
in
p egnan
women.
The
aim
o
his
cu en
s udy
was
o
analyze
in a-indi idual
changes
in
TSH
du ing
he
fi s
hal
o
p egnancy
in
women
wi h
TSH
le els
highe
han
2.5
mIU/L
in
ea ly
p egnancy.
Me hods:
An
obse a ional,
p ospec i e
s udy
was
conduc ed
on
243
heal hy
p egnan
women
in
he
fi s
imes e
o
p egnancy.
Thy oid
unc ion
was
assessed
by
es ing
TSH
and
ee
T4
le els.
A
subg oup
o
women
wi h
TSH
le els
>2.5
mIU/L
unde wen
addi ional
es s
(TSH,
ee
T4,
pe oxidase
an ibodies).
In o ma ion
on
die a y
iodine
in ake
and/o
iodine
supplemen s
was
also
eco ded.
Resul s:
Mean
TSH
le el
was
1.89
mIU/L
( ange
0.024---6.48
mIU/L),
and
mean
FT4
le el
was
1.19
ng/dL
( ange
0.80---1.90
ng/dL).
Fi y-eigh
women
(23.8%)
had
TSH
le els
>
2.5
mIU/L
in
he
fi s
imes e
o
p egnancy,
and
addi ional
hy oid
unc ion
es s
we e
pe o med
in
27
women.
TSH
le els
significan ly
dec eased
om
he
fi s
o
he
second
es
(3.59
±
0.92
mIU/L
s
2.81
±
1.06
mIU/L
espec i ely;
p
<
0.01),
and
he
dec ease
was
significan ly
g ea e
in
p egnan
women
who
used
iodized
sal
as
compa ed
o
hose
who
did
no
(1.16
±
0.65
mIU/L
s
0.19
±
0.93
mIUI/L
espec i ely;
p
<
0.01).
A
posi i e
co ela ion
was
ound
be ween
he
ime
elapsed
o
he
second
measu emen
(24.3
±
17.2
days;
ange
8---58)
and
he
dec ease
in
TSH
le els
(
=
0.40;
p
=
0.038).
∗Co esponding
au ho .
E-mail
add ess:
[email p o ec ed]
(C.
Faja do-Mon a˜
nana).
h p://dx.doi.o g/10.1016/j.endinu.2017.04.002
2530-0164/©
2017
SEEN.
Published
by
Else ie
Espa˜
na,
S.L.U.
All
igh s
ese ed.
TSH
a iabili y
in
ea ly
ges a ion
289
Conclusion:
TSH
le els
showed
a
con inuous,
uni o m
dec ease
du ing
he
fi s
hal
o
p egnancy
in
women
wi h
alues
sligh ly
abo e
he
no mal
ange.
P egnan
women
who
used
iodized
sal
we e
mo e
likely
o
ha e
dec eased
TSH
le els
in
a
second
es .
©
2017
SEEN.
Published
by
Else ie
Espa˜
na,
S.L.U.
All
igh s
ese ed.
PALABRAS
CLAVE
TSH;
Pun o
de
co e;
P ime
imes e
Va iabilidad
in a-indi idual
de
los
ni eles
TSH
en
muje es
sanas
en
p ime
imes e
de
ges ación
Resumen
Obje i o:
La
TSH
es
el
pa áme o
más
acep ado
pa a
e alua
la
unción
i oidea,
especialmen e
en
muje es
emba azadas.
El
obje i o
del
p esen e
es udio
ue
analiza
los
cambios
in aindi-
iduales
de
TSH
du an e
la
p ime a
mi ad
de
la
ges ación,
en
aquellos
casos
en
los
que
la
TSH
en
las
p ime as
e apas
de
la
ges ación
ue
supe io
a
2,5
mUI/L.
Mé odos:
Es udio
obse acional
p ospec i o
que
incluyó
a
243
muje es
emba azadas
sanas
en
el
p ime
imes e
de
ges ación.
Se
es udió
unción
i oidea
median e
TSH
y
T4
lib e.
Un
subg upo
de
muje es
con
TSH>
2,5
mUI/L
ue on
some idas
a
un
segundo
análisis
(TSH,
T4
lib e,
an icue pos
an ipe oxidasa).
También
se
egis ó
in o mación
sob e
la
inges a
de
yodo
con
la
die a
y/o
suplemen os.
Resul ados:
La
TSH
media
ue
de
1,89
mUI/L
( ango
0,024-6,48
mUI/L),
y
la
T4
lib e
media
ue
de
1,19
ng/dL
( ango
0,80-1,90
ng/dL).
El
23,8%
(58
muje es)
p esen a on
TSH>
2,5
mUI/L
en
el
p ime
imes e
de
ges ación,
ealizándose
una
segunda
alo ación
en
27
pacien es.
La
TSH
disminuyó
significa i amen e
del
p ime
al
segundo
análisis
(3,59
±
0,92
mUI/L
s.
2,81
±
1,06
mUI/L
espec i amen e,
p
<0,01).
La
TSH
disminuyó
significa i amen e
más
en
aquellas
muje es
emba azadas
que
consumie on
sal
yodada
que
en
aquellas
que
no
lo
hicie on
(1,16
±
0,65
mUI/L
s.
0,19
±
0,93
mUI/L
espec i amen e,
p
<
0,01).
Hubo
una
co elación
pos-
i i a
en e
el
iempo
anscu ido
pa a
una
segunda
de e minación
(24,3
±
17,2
días,
ango
8-58
días),
y
la
educción
en
los
ni eles
de
TSH
( =
0,40;
p
=
0,038).
Conclusión:
La
disminución
de
los
ni eles
de
TSH
con
la
edad
ges acional
es
uni o memen e
con inua
a
lo
la go
de
la
p ime a
mi ad
de
la
ges ación
en
aquellos
casos
con
TSH
lige amen e
po
encima
del
ango
suge ido
de
no malidad.
Las
muje es
emba azadas
que
consumían
sal
yodada
enían
más
p obabilidades
de
educi
los
ni eles
de
TSH
en
un
segundo
análisis.
©
2017
SEEN.
Publicado
po
Else ie
Espa˜
na,
S.L.U.
Todos
los
de echos
ese ados.
In oduc ion
Thy oid
ho mones
(TH)
a e
in ol ed
in
essen ial
unc ions
such
as
soma ic
g ow h,
me abolic
egula ion
and
neu ode-
elopmen ,
so
hey
play
a
pi o al
ole
du ing
ges a ion.1 --- 3
The
de eloping
emb yo/ e us
is
ex emely
dependen
on
ma e nal
supply
o
TH,
pa icula ly
in
he
fi s
imes e
o
p egnancy,
since
i s
hy oid
gland
will
be
non- unc ional
un il
mid
ges a ion.4
A
g owing
body
o
e idence
suppo s
he
associa ion
o
ma e nal
hy oid
dys unc ion
(e en
mild
o
mode a e
dys-
unc ions)
in
ea ly
s ages
o
e al
de elopmen
and
he
incidence
o
obs e ic
and/o
pe ina al
complica ions.5This
conce n
has
led
scien ific
socie ies
o
de elop
se e al
clini-
cal
guidelines
o e
he
las
ew
yea s.6 --- 8
Al hough
he
dilemma
be ween
a
uni e sal
hy oid
sc eening
o
a
case-finding
s a egy
o
p egnan
women
emains
con o e sial9and
he e
is
no
fi m
consensus
on
how
hy oid
dys unc ion
should
be
diagnosed,
he
main
in e -
es
has
ocused
on
es ablishing
eliable,
imes e -specific
cu -o
alues
o
hy oid
unc ion
pa ame e s
which
allow
o
iden i y
he
po en ial
isk
o
ma e nal
and/o
neona al
ad e se
ou comes.10
I
has
been
ecommended
o
define
popula ion-based
imes e -specific
e e ence
in e als;
howe e ,
only
iodine
su ficien
women
wi hou
an i- hy oid
pe oxidase
(an i-
TPO)
an ibodies
should
be
included
in
he
s anda dizing
popula ion,11 and
many
comme cial
labo a o ies
s ill
do
no
p o ide
hese
e e ence
anges.12
In
2011
he
Ame ican
Thy oid
Associa ion
(ATA)
p oposed,
in
absence
o
specific
e e ence
in e als,
a
2.5
mUI/L
cu -o
alue
o
he
fi s - imes e .6Since
hen,
di -
e en
s udies
wo ldwide
ha e
demons a ed
ha
TSH
and
FT4
le els
in
se e al
se ings
a e
ou side
he
no -
mal
imes e -specific
e e ence
anges
used
o
Uni ed
S a es
popula ion,13 esul ing
in
po en ial
o e diagnosis
o
hypo hy oidism
in
hose
popula ions
when
he
cu -o
alues
p oposed
by
he
ATA
a e
used.14
Du ing
he
fi s
imes e
o
ges a ion,
he
TSH
le els
a e
pa ially
supp essed
due
o
he
s imula o y
e ec
o
human
cho ionic
gonado ophin
(hCG)
on
he
hy oid
gland.
The
supp essi e
e ec
o
hCG
on
TSH
in
he
fi s
imes e
can
290
M.
Mu illo-Llo en e
e
al.
be
modula ed
by
di e en
ac o s
such
as
hy oid
au oim-
muni y,
body
mass
index,
smoking
habi ,
age
o
pa i y.15,16
A
he
same
ime,
a
ecen
s udy
has
shown
how
widely
TSH
e e ence
limi s
di e
wi hin
he
fi s
imes e
o
p egnancy.17 While
he
lowe
TSH
in
weeks
9---12
o
p eg-
nancy
a e
e iden ly
explained
by
he
high
hCG
p oduc ion,
conside ably
highe
TSH
alues
we e
obse ed
ea lie
han
6
weeks
o
ges a ion,
which
a e
simila
o
non-p egnancy
e e ence
limi s.
On
he
o he
hand,
some
s udies
ha e
demons a ed
ha
TSH
le els
show
high
wi hin-pe son
consis ency
be ween
imes e s,
hough
indi idual
ends
o
each
woman
should
be
aken
in o
accoun .18,19
Gi en
his
backg ound,
ou
aim
was
o
e alua e
he
in a-
indi idual
a ia ion
o
TSH
du ing
he
fi s
hal
o
ges a ion
in
hose
cases
o
‘‘po en ially
high’’
TSH
in
he
fi s
imes e .
Subjec s
and
me hods
S udy
subjec s
We
ca ied
ou
a
longi udinal
s udy
on
243
heal hy
Caucasian
women
a
he
Hospi al
Uni e si a io
de
La
Ribe a
(HULR),
Alzi a
(Valencia,
Spain),
a
hei
fi s
an ena al
isi
(ges a-
ional
weeks
5---13),
om
Sep embe
2014
o
Janua y
2015.
Inclusion
c i e ia
we e
age
18
o
olde ,
caucasian
e hnici y,
and
ges a ional
age
up
o
and
including
week
13
o
ameno -
hea.
All
pa icipan s
unde wen
an
obs e ic
examina ion
o
exclude
ma e nal
and/o
e al
isk
ac o s.
Re usal
o
pa icipa e,
non-caucasian
e hnic
g oups,
ges-
a ional
age
ou
o
fi s
imes e ,
high- isk
p egnancies,
pe sonal
his o y
o
hy oid
o
any
o he
endoc ine
diso de s
and/o
use
o
d ugs
which
in e e e
wi h
iodine
me abolism
we e
conside ed
as
exclusion
c i e ia.
Fo
hose
p egnan
women
who
had
a
TSH
>
2.5
mUI/L
a
he
fi s
isi
(23.8%),
a
subsequen
ollow-up
and
a
sec-
ond
hy oid
unc ion
es
we e
pe o med
in
27
pa ien s
(Fig.
1).
The
second
es
included
he
s udy
o
an i- hy oid
pe oxidase
(an i-TPO)
an ibodies.
Women
en olled
we e
asked
specifically
abou
hei
use
o
supplemen s
con aining
po assium
iodide
(KI),
i on,
olic
acid
and/o
mul i i amins
du ing
he
p egnancy.
The
con-
sump ion
o
iodine- ich
oods
was
assessed
h ough
a
ood
equency
ques ionnai e
(FFQ)
p e iously
alida ed
in
Span-
ish
popula ion.20
All
p egnan
women
p o ided
as ing
pe iphe al
enous
blood
samples
om
an
an ecubi al
ein
ea ly
in
he
mo ning.
Samples
we e
cen i uged
and
se um
was
s o ed
a
−40 ◦C
un il
he
analysis.
The
s udy
was
app o ed
by
he
E hics
and
Clinical
Resea ch
Commi ee
o
he
Hospi al
Uni e si a io
de
La
Rib-
e a
and
w i en
in o med
consen
was
ob ained
om
all
he
pa icipan s.
This
wo k
complies
wi h
he
p inciples
laid
down
in
he
Decla a ion
o
Helsinki.
Labo a o y
p ocedu es
The
TSH
and
F ee
T4
(FT4)
we e
measu ed
by
chemi-
luminescence
h ough
he
ADVIA
Cen au
immunoassay
sys em
(Siemens
Heal hca e
Diagnos ics,
Ge many).
Fo
TSH,
he
analy ical
measu emen
ange
gi en
by
he
manu-
Second hy oid unc ion
es N= 32
27 TSH > 2.5 mUI/L
5 TSH < 0.27 mUI/L
P egnan women ec ui ed in
i s imes e o ges a ion
(N=275)
Excluded:
-17 non-caucasian women
-5 Ges acional age > 13 weeks
-5 Hypo hy oidism
-
2 Aged < 18 yea s
-2 Misca iages
-1 Hype hy oidism
Elegible and en olled
(N=243)
P egnan women wi h
TSH <2.5 mUI/L
(N=185)
∗9 women TSH <0.27 mUI/L
(non p egnan lowe e e ence
alue)
P egnan women wi h
TSH >2.5 mUI/L
(N=58)
Figu e
1
Flow
diag am
o
pa icipan s.
ac u e
was
0.27---5
mUI/L,
and
he
low,
medium
and
high
coe ficien
o
a ia ion
(CV)
was
4.45%,
3.77%
and
5.17%
espec i ely.
Fo
FT4,
he
analy ical
measu emen
ange
gi en
by
he
manu ac u e
was
0.9---1.7
ng/dL,
and
he
low,
medium
and
high
coe ficien
o
a ia ion
(CV)
was
4.16%,
4.58%
and
3.44%
espec i ely.
An i- hy oid
pe oxidase
(an i-
TPO)
was
measu ed
by
a
adioimmunome ic
assay
(Immuli e
2000;
Siemens
Heal hca e
Diagnos ics,
Ge many).
An i-TPO
we e
conside ed
posi i e
i
he
i e
was
>35
mIU/L.
S a is ical
analysis
The
quan i a i e
a iables
we e
measu ed
as
he
mean
±
s anda d
de ia ion
o
mean
( ange)
and
he
quali a i e
a iables
as
pe cen ages.
The
con as
hypo he-
sis
o
wo
samples
was
e alua ed
wi h
he
S uden ’s
- es
o
quan i a i e
a iables
and
Chi-squa ed
es
in
cases
o
ca ego ical
ones.
In
he
e en
ha
a iables
did
no
adjus
o
no mali y,
a
K uskall---Wallis
es
was
done.
Fo
he
adjus men
o
he
model
o
o he
a iables,
wo-
o
mul i-way
analysis
o
he
a iance
(ANOVA)
we e
designed,
in oducing
he
con inuous
a iables
as
co a iables.
The
co ela ion
be ween
a iables
was
de e mined
using
he
Spea man
es ,
designing
mul iple
eg ession
models
in
hose
cases
whe e
i
was
desi ed
o
p edic
he
a iance
adjus ed
o
o he
a iables,
besides
he
main
a iable.
In
all
cases
he
ejec ion
le el
o
a
null
hypo hesis
was
˛
<
0.05.
TSH
a iabili y
in
ea ly
ges a ion
291
Resul s
The
clinical
cha ac e is ics
o
he
p egnan
women
included
in
he
s udy
a e
shown
in
Table
1.
All
women
who
we e
e en ually
included
had
low
isk
ges a ions
as
assessed
by
obs e ical
and
ul asound
scan
a
he
en ollmen
ime.
We
ound
no
di e ences
in
clinical
a iables
o
he
p egnan
women
acco ding
o
he
ini ial
le el
o
TSH
(up
o
2.5
mUI/L
o
abo e
his
le el).
In
o de
o
find
ou
he
iodine
in ake,
all
p egnan
women
we e
asked
abou
he
consump ion
o
iodine- ich
oods
h ough
a
FFQ.
They
also
decla ed
hei
use
o
supplemen s
du ing
p egnancy
(KI,
olic
acid,
mul i i amins
and/o
i on).
No
di e ences
we e
ound
in
he
consump ion
o
iodized
sal ,
fish
o
dai y
p oduc s
be ween
p egnan
women
wi h
no mal
TSH
and
hose
who
had
TSH
>2.5
mUI/L
(Table
2).
Mean
TSH
was
1.89
mUI/L
( ange
0.024---6.48
mUI/L).
F om
243
women,
185
had
no mal
alues
o
TSH
and
58
had
alues
>2.5
mUI/L
(1.44
±
0.58
mUI/L
s
3.36
±
0.85
mUI/L
espec i ely,
p
<
0.01).
Mean
FT4
was
1.19
ng/dL
( ange
0.80---1.90
ng/dL).
No
significan
di e ences
we e
ound
in
FT4
le els
be ween
women
wi h
no mal
TSH
and
hose
who
had
TSH
>
2.5
mUI/L
(1.19
±
0.16
ng/dL
s
1.17
±
0.18
ng/dL
espec i ely;
p
=
0.58).
The e
was
no
di e ence
in
means
o
TSH
acco ding
o
he
in ake
o
iodized
sal ,
fish
o
dai y
p oduc s
(da a
no
shown).
The
consump ion
o
KI,
mul i i amins,
olic
acid
o
i on
did
no
show
significan
di e ences
in
TSH
and
FT4
le els
(da a
no
shown).
TSH
showed
a
weak
co ela ion
wi h
body
mass
index
(
=
0.12;
p
=
0.04)
bu
no
wi h
o he
a iables
such
as
ma e nal
age,
weigh ,
pa i y
o
ges a ional
age.
FT4
did
no
show
any
co ela ion
wi h
o he
a iables.
On
27
women
who
showed
TSH
>2.5
mUI/L,
a
second
es
was
pe o med
which
included
TSH,
FT4
and
an i-TPO
an i-
bodies.
Only
2
cases
o
an i-TPO
>35
UI
we e
ound.
TSH
dec eased
significan ly
om
he
fi s
o
he
second
anal-
ysis
(3.59
±
0.92
mUI/L
s
2.81
±
1.06
mUI/L
espec i ely;
p
<
0.01)
bu
he e
was
a
mode a e
co ela ion
be ween
bo h
figu es
(
=
0.66;
p
<
0.01).
Fig.
2
shows
he
a iabil-
i y
o
TSH
wi hin
each
pa icipan .
FT4
le els
emained
s eady
(1.16
±
0.16
ng/dL
s
1.07
±
0.29
ng/dL
espec i ely;
p
=
0.21)
and
no
co ela ion
be ween
bo h
measu emen s
was
ound.
Elapsed
ime
be ween
he
fi s
and
he
sec-
ond
analysis
anged
om
8
o
58
days
(24.3
±
17.2,
median
16
days),
and
i
was
indi idualized
aking
in o
accoun
p e-
ious
TSH
le el.
The e
was
a
posi i e
co ela ion
be ween
he
elapsed
ime
and
he
educ ion
in
TSH
le els
(
=
0.40;
p
=
0.038).
The
eg ession
model
shows
how
TSH
dec eased
0.022
mUI/L
pe
day
elapsed
om
he
fi s
o
he
second
analysis.
The
mean
di e ence
be ween
fi s
and
second
TSH
was
−0.69
mUI/L
( anged
om
−2.49
o
1.38
mUI/L).
No
sig-
nifican
di e ences
in
TSH
dec ease
we e
ound
acco ding
o
ges a ional
age
a
he
fi s
analysis
(below
6
weeks,
6 --- 9
weeks
and
10---13
weeks).
TSH
d opped
mo e
signi -
ican ly
in
hose
p egnan
women
who
consumed
iodized
sal
han
in
hose
ones
who
did
no
(1.16
±
0.65
mUI/L
s
0.19
±
0.93
mUI/L
espec i ely;
p
<
0.01),
bu
he
di e ence
was
no
significan
wi h
ega d
o
iodine
supplemen s
(da a
no
shown).
A e
a
second
hy oid
es ,
le o hy oxine
ea -
men
was
in oduced
in
18.5%
(5/27)
o
p egnan
women.
Discussion
This
is
he
fi s
s udy
ha
analyzes
he
e olu ion
and
in a-
indi idual
a iabili y
o
TSH
along
he
fi s
hal
o
ges a ion
when
i
is
>2.5
mUI/L
in
heal hy
p egnan
women.
Ou
main
findings
a e
as
ollows:
(a)
TSH
le els
uni o mly
dec ease
along
he
fi s
imes e
o
ges a ion
in
cases
sligh ly
abo e
he
no mal
ange,
and
(b)
p egnan
women
who
consumed
iodized
sal
we e
mo e
likely
o
educe
TSH
le els
in
a
second
analysis.
The
s udy
o
hy oid
unc ion
in
fi s
imes e
o
p eg-
nancy
has
ecei ed
special
a en ion
in
he
las
decade,
in
o de
o
p e en
e al
and
ma e nal
complica ions
and
Table
1
Main
cha ac e is ics
o
pa icipan s
and
compa ison
be ween
he
wo
g oups
(acco ding
o
TSH
le els).
All
pa icipan s
(N
=
243)
TSH
≤
2.5
mUI/L
(n
=
185)
TSH
>
2.5
mUI/L
(n
=
58)
p
Age
(yea s)
31.02
(18---45)
30.98
(18---45)
31.14
(19---42)
0.830
(n.s.)a
Weigh
(kg)
64.19
(41.40---107.00)
63.79
(41.40---107.00)
65.46
(48.50---93.70)
0.366
(n.s.)a
BMI
(kg/m2)
23.73
(15.00---37.00)
23.64
(15.00---37.00)
24.00
(19.00---35.00)
0.581
(n.s.)a
Ges a ional
age
(weeks)
Below
6
weeks
139
(57.2%)
105
(56.8%)
34
(58.6%)
6 --- 9
weeks
71
(29.2%)
53
(28.6%)
18
(31.0%)
0.705
(n.s)b
10---13
weeks
33
(13.6%)
27
(14.6%)
6
(10.4%)
Pa i y
Fi s
ges a ion
106
(43.6%)
82
(44.3%)
24
(41.4%)
Second
ges a ion
87
(35.8%)
64
(34.6%)
23
(39.7%)
0.779
(n.s.)b
Thi d
o
mo e
50
(20.6%)
39
(21.1%)
11
(19.0%)
P e ious
misca iage
Yes
63
(25.9%)
52
(28.1%)
11
(19.0%)
0.166
(n.s.)b
No
180
(74.1%)
133
(71.9%)
47
(81.0%)
aS uden ’s
es
o
di e ence
o
means.
bChi-squa e
es
o
ca ego ical
a iables.
292
M.
Mu illo-Llo en e
e
al.
Table
2
Iodine
in ake,
use
o
supplemen s
and
compa ison
be ween
he
wo
g oups
(acco ding
o
TSH
le els).
All
pa icipan s
(N
=
243)
TSH
≤
2.5
mUI/L
(n
=
185)
TSH
>
2.5
mUI/L
(n
=
58)
p
Iodized
sal
Yes
120
(49.4%)
93
(50.3%)
27
(46.6%)
0.621
No
123
(50.6%)
92
(49.7%)
31
(53.4%)
Fish
consump ion
Once
a
week
210
(86.4%)
161
(87.0%)
49
(84.5%)
0.622
No
consump ion
33
(13.6%)
24
(13.0%)
9
(15.5%)
Milk/Dai y
p oduc s
Daily
consump ion 210
(86.4%) 158
(85.4%) 52
(89.7%) 0.410
No
egula
in ake 33
(13.6%) 27
(14.6%) 6
(10.3%)
Use
o
supplemen s
Po assium
iodide
Yes
167
(68.7%)
124
(67.0%)
43
(74.1%)
0.308
No
76
(31.3%)
61
(33.0%)
15
(25.9%)
Mul i i amins
Yes 60
(24.7%) 46
(24.9%) 14
(24.1%)
0.911
No
183
(75.3%) 139
(75.1%) 44
(75.9%)
Folic
acid
Yes
38
(15.6%)
26
(14.1%)
12
(20.7%)
0.225
No
205
(84.4%)
159
(85.9%)
46
(79.3%)
I on
Yes
93
(38.3%)
73
(39.5%)
20
(34.5%)
0.496
No
150
(61.7%)
112
(60.5%)
38
(65.5%)
he
ad e se
e ec s
on
neu ocogni i e
de elopmen
o
o sp ing.21 Ne e heless,
he
g owing
unde s anding
o
hy-
oid
unc ion
in
ea ly
s ages
o
ges a ion
highligh
he
p ac icali ies
o
he
hy oid
unc ion
es s
in
p egnancy.22
Du ing
he
fi s
imes e ,
human
cho ionic
gonado opin
(hCG)
induces
a
ansien
lowe ing
o
TSH
concen a ions.
Howe e ,
ecen
s udies
ha e
shown
how
hCG
le els
can
be
significan ly
influenced
by
ma e nal
smoking,
BMI,
pa i y,
e hnici y,
e al
gende ,
placen al
weigh
and/o
hype emesis
g a ida um
symp oms.23 The
p ac ical
implica ions
o
hese
obse a ions
a e
ha
TSH
concen a ions
can
consequen ly
a y
acco ding
o
hese
ac o s,
e en
wi hin
he
same
pop-
ula ion.
Fu he mo e,
ges a ional
age
has
a
c ucial
e ec
along
he
fi s
imes e :
while
hCG
eaches
a
peak
a
9---11
weeks
coinciden
wi h
a
all
in
TSH,
TSH
concen a ion
a
4 --- 6
weeks
o
ges a ion
is
he
same
as
in
non-p egnan
women.13,17 In
ou
s udy,
hal
o
he
p egnan
women
who
had
TSH
>2.5
mUI/L
we e
es ed
be o e
6
weeks
o
ges a ion.
Di e en
s udies24,25 ha e
demons a ed
ha
TSH
con-
cen a ions
dec ease
significan ly
om
he
se en h
week
o
p egnancy
o
hei
lowes
poin
be ween
ges a ional
weeks
10
and
11.
The
mean
ime
elapsed
be ween
fi s
and
second
TSH
de e mina ion
in
ou
wo k
was
24.3
days,
p esumably
coinciding
wi h
he
dec ease
in
TSH
o
i s
lowes
poin
o
he
end
o
he
fi s
imes e .
In
his
ega d,
ou
esul s
a e
consis en
wi h
p e ious
s udies
and
also
suppo
he
conclu-
sion
ha
he
use
o
uni o m
limi s
o
TSH
o
he
en i e
fi s
imes e
may
lead
o
equen
misclassifica ion17 and,
wha
is
mo e
se ious,
he
indica ion
o
inapp op ia e
ea men
wi h
hy oxine.26
TSH
local
e e ence
alues
o
fi s
imes e
o
ges a-
ion
(0.128---4.455
mUI/L)
we e
ob ained
in
pa allel
wi h
he
las
pe iod
o
his
s udy,
he e o e
jus i ying
he
ac
ha
in
many
cases
TSH
was
no
epea ed.
On
he
o he
hand,
ou
s udy
shows
ha
hose
p egnan
women
who
consumed
iodized
sal
had
lowe
le els
o
TSH
in
hei
second
analysis,
bu
his
e ec
did
no
appea
in
cases
o
supplemen a ion
wi h
KI.
In
his
ega d,
Mole i
e
al.27
compa ed
hy oid
unc ion
du ing
p egnancy
in
h ee
g oups
o
p egnan
women:
women
who
had
aken
iodized
sal
a
leas
o
2
yea s
be o e
becoming
p egnan ,
o he s
who
ook
150
␮g
o
KI
and
a
hi d
g oup
who
did
no
ake
iodized
sal
no
KI
supplemen s.
The
lowes
TSH
concen a ions
we e
consis en ly
obse ed
in
he
iodized
sal
g oup.
San iago
e
al.28 also
ound
lowe
TSH
le els
in
he
fi s
imes e
in
women
who
we e
aking
iodized
sal
compa ed
o
hose
who
ook
KI
supplemen s,
al hough
he
di e ence
was
no
significan
(p
=
0.06).
The
p esen
s udy
is
cons ained
by
some
limi a ions:
al hough
we
only
s udied
he
cases
wi h
TSH
>2.5
mUI/L,
ou
esul s
we e
consis en
wi h
p e ious
s udies
wi h
la ge
sample
sizes.
The
lack
o
u ina y
iodine
concen a ion
(UIC)
did
no
allow
us
o
sea ch
o
po en ial
co ela ions
be ween
hy oid
unc ion
and
iodine
s a us.
Howe e ,
he
in ake
o
iodized
sal
was
associa ed
wi h
a
significan
e ec
on
TSH
dec ease
which
has
no
been
seen
in
cases
o
consump ion
o
KI
supplemen s.
To
he
bes
o
ou
knowledge
his
is
he
fi s
s udy
o
demons a e
ha
TSH
declines
uni o mly
along
he
fi s
imes e ,
so
exac ly
he
same
women
can
be
classified
in
no mal
o
pa hological
TSH
alues
only
depending
on

TSH
a iabili y
in
ea ly
ges a ion
293
ATSH a iabili y
TSH a iabili y
7000
6000
5000
4000
3000
3000
1000
7000
6000
5000
4000
3000
2000
1000
.000
1
2
3
4
5
6
7
8
910 11 12 13 14 15 16 17
Case numbe
Case numbe
TSH (1s de e mina ion)
TSH (1s de e mina ion)
TSH (2nd de e mina ion)
TSH (2nd de e mina ion)
18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
12345678910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
Value (mUI/mL)Value (mUI/mL)
B
Figu e
2
(A)
In a-indi idual
TSH
a iabili y
in
32
women
wi h
a
second
hy oid
unc ion
es .
(B)
In a-indi idual
a iabili y
in
27
women
wi h
TSH
>2.5
mUI/L.
hei
ges a ional
age
a
he
ime
o
hy oid
es .
This
ac
ein o ces
he
need
o
es ablish
a
p ecise
iming
o
s udy
hy oid
unc ion
in
he
fi s
imes e
o
ges a ion,
necessa -
ily
adjus ed
by
ges a ional
weeks,
in
o de
o
a oid
inco ec
diagnosis
and
o e ea men .
Au ho s’
con ibu ions
MTM,
and
CFM
designed
he
s udy
and
MTM,
RVC,
and
CFM
and
JGV
conduc ed
fieldwo k.
MTP,
MPB
and
IV
en e ed
he
da a
o
analyses.
MPB
and
IV
conduc ed
he
s a is ical
analyses.
MTM,
MPB,
RVC,
CFM
and
IV
w o e
he
fi s
d a
o
he
manusc ip
and
inco po a ed
sugges ions
om
all
he
coau ho s.
All
he
au ho s
ha e
ead
and
app o ed
he
final
e sion
o
his
a icle.
Funding
This
esea ch
did
no
ecei e
any
specific
g an
om
any
unding
agency
in
he
public,
comme cial
o
no - o -p ofi
sec o .
294
M.
Mu illo-Llo en e
e
al.
Conflic
o
in e es
The
au ho s
decla e
ha
he e
is
no
conflic
o
in e es
ha
could
be
pe cei ed
as
p ejudicing
he
impa iali y
o
he
esea ch
epo ed.
Acknowledgemen s
The
au ho s
a e
g a e ul
o
p egnan
women
who
accep ed
o
pa icipa e
in
he
s udy.
We
a e
also
g a e ul
o
Ma io
O u˜
no,
and
he
whole
Midwi e y
eam
om
he
Obs e -
ic
and
Gynecology
Depa men ,
Hospi al
Uni e si a io
de
la
Ribe a.
Re e ences
1.
Fo head
AJ,
Fowden
AL.
Thy oid
ho mones
in
e al
g ow h
and
p epa um
ma u a ion.
J
Endoc inol.
2014;221:87---103.
2.
Ande sen
SL,
Olsen
J,
Lau be g
P.
Foe al
p og amming
by
ma e -
nal
hy oid
disease.
Clin
Endoc inol
(Ox ).
2015;83:751---8.
3.
Flaman
F,
Koibuchi
NBJ.
Edi o ial
‘‘Thy oid
ho mone
in
b ain
and
b ain
cells’’.
F on
Endoc inol
(Lausanne).
2015;6:99.
4.
Pa el
J,
Lande s
K,
Li
H,
Mo ime
RH,
Richa d
K.
Deli e y
o
ma e nal
hy oid
ho mones
o
he
e us.
T ends
Endoc inol
Me ab
[In e ne ],
22.
Else ie
L d.;
2011.
p.
164---70.
5.
Neg o
R,
S agna o-G een
A.
Clinical
aspec s
o
hype hy oidism
hypo hy oidism,
and
hy oid
sc eening
in
p egnancy.
Endoc
P ac .
2014;20:1---34.
6.
S agna o-G een
A,
Abalo ich
M,
Alexande
E,
Azizi
F,
Mes man
J,
Neg o
R,
e
al.
Guidelines
o
he
Ame ican
Thy oid
Associa-
ion
o
he
diagnosis
and
managemen
o
hy oid
disease
du ing
p egnancy
and
pos pa um.
Thy oid.
2011;21:1081---125.
7.
De
G oo
L,
Abalo ich
M,
Alexande
EK,
Amino
N,
Ba bou
L,
Cobin
RH,
e
al.
Managemen
o
hy oid
dys unc ion
du ing
p eg-
nancy
and
pos pa um:
an
endoc ine
socie y
clinical
p ac ice
guideline.
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