Relationship of thyroid-stimulating hormone levels to development of dyslipidemia and determination of an ideal cut-off point to start replacement therapy

Abstract

Background and objective:
There are studies showing a strong association between thyroid dysfunction and increased cardiovascular risk due to lipid profile changes. The purpose of this study was to assess the degree of association and predictive power of thyroid-stimulating hormone (TSH) levels in relation to lipid profile changes, identifying the TSH cut-off point beyond which lipid changes occur.

Patients and methods:
A cross-sectional, retrospective study in Quito (Ecuador) conducted from January 2004 to December 2008 on patients first attending the endocrinology department.

Results:
A total of 278 histories were analyzed, and a 36.3% prevalence of subclinical hypothyroidism was found. No association was found between sex and cholesterol or between sex and low density lipoprotein (LDL). However, associations were found between sex and dyslipidemia, sex and body mass index (BMI), and sex and TSH. Linear regression analysis between LDL and TSH, cholesterol and TSH, and BMI and TSH showed significant associations in all cases, with Pearson R2 coefficients of 0.80, 0.81, and 0.85 respectively.

Conclusions:
TSH levels show a statistically significant association to total cholesterol and LDL levels, but are not a good clinical predictor in this process. A cut-off point beyond which replacement therapy should be started to prevent occurrence of dyslipidemia cannot therefore be established.

Full text

Endocrinol
Nutr.
2012;59(10):575---582
ENDOCRINOLOGÍA
Y
NUTRICIÓN
www.elsevier.es/endo
ORIGINAL
ARTICLE
Relationship
of
thyroid-stimulating
hormone
levels
to
development
of
dyslipidemia
and
determination
of
an
ideal
cut-off
point
for
start
replacement
therapy夽
Vanessa
Sarzosa
Terán a,∗,
María
Augusta
Astudillo
Calleb
aServicio
de
Medicina
Interna,
Hospital
de
Atuntaqui,
Atuntaqui,
Ecuador
bServicio
de
Medicina
Interna,
Hospital
de
Riobamba,
Riobamba,
Ecuador
Received
1
February
2012;
accepted
10
July
2012
Available
online
16
January
2013
KEYWORDS
Hypothyroidism;
Subclinical
hypothyroidism;
Low
density
lipoproteins
cholesterol;
Total
cholesterol;
Thyroid
stimulating
hormone;
Replacement
therapy
with
thyroxine
Abstract
Background
and
objective: There
are
studies
showing
a
strong
association
between
thyroid
dysfunction
and
increased
cardiovascular
risk
due
to
lipid
profile
changes.
The
purpose
of
this
study
was
to
assess
the
degree
of
association
and
predictive
power
of
thyroid-stimulating
hormone
(TSH)
levels
in
relation
to
lipid
profile
changes,
identifying
the
TSH
cut-off
point
beyond
which
lipid
changes
occur.
Patients
and
methods:
A
cross-sectional,
retrospective
study
in
Quito
(Ecuador)
was
conducted
from
January
2004
to
December
2008
on
patients
first
attending
the
endocrinology
department.
Results:
A
total
of
278
histories
were
analyzed,
and
a
36.3%
prevalence
of
subclinical
hypothy-
roidism
was
found.
No
association
was
found
between
sex
and
cholesterol
or
between
sex
and
low
density
lipopro-
tein
(LDL).
However,
associations
were
found
between
sex
and
dyslipidemia,
sex
and
body
mass
index
(BMI),
and
sex
and
TSH.
Linear
regression
analysis
between
LDL
and
TSH,
cholesterol
and
TSH,
and
BMI
and
TSH
showed
significant
associations
in
all
cases,
with
Pearson
R2coefficients
of
0.80,
0.81,
and
0.85
respectively.
Conclusions:
TSH
levels
show
a
statistically
significant
association
to
total
cholesterol
and
LDL
levels,
but
are
not
a
good
clinical
predictor
in
this
process.
A
cut-off
point
beyond
which
replace-
ment
therapy
should
be
started
to
prevent
occurrence
of
dyslipidemia
cannot
therefore
be
established.
©
2012
SEEN.
Published
by
Elsevier
España,
S.L.
All
rights
reserved.
夽Please
cite
this
article
as:
Sarzosa
Terán
V,
Astudillo
Calle
MA.
Concentraciones
de
tirotropina
con
relación
al
desarrollo
de
dislipidemia
y
determinación
de
punto
de
corte
ideal
para
el
inicio
de
tratamiento
sustitutivo.
Endocrinol
Nutr.
2012;59:575---82.
∗Corresponding
author.
E-mail
address:
vanealej uio@yahoo.es
(V.
Sarzosa
Terán).
2173-5093/$
–
see
front
matter
©
2012
SEEN.
Published
by
Elsevier
España,
S.L.
All
rights
reserved.

576
V.
Sarzosa
Terán,
M.A.
Astudillo
Calle
PALABRAS
CLAVE
Hipotiroidismo;
Hipotiroidismo
subclínico;
Colesterol
lipoproteínas
de
baja
densidad;
Colesterol
total;
Tirotropina;
Tratamiento
sustitutivo
con
tiroxina
Concentraciones
de
tirotropina
con
relación
al
desarrollo
de
dislipidemia
y
determinación
de
punto
de
corte
ideal
para
el
inicio
de
tratamiento
sustitutivo
Resumen
Antecedentes
y
objetivo:
Hay
estudios
que
demuestran
una
gran
asociación
entre
disfunción
tiroidea
e
incremento
del
riesgo
cardiovascular
por
alteraciones
del
perfil
lipídico.
El
objetivo
de
este
estudio
es
determinar
el
grado
de
asociación
y
poder
predictor
de
las
con-
centraciones
de
tirotropina
(TSH)
en
relación
con
alteraciones
del
perfil
lipídico,
identificando
el
punto
de
corte
de
TSH
tras
el
cual
se
producen
alteraciones
lipídicas.
Material
y
método: Estudio
trasversal
retrospectivo
en
Quito
(Ecuador)
en
el
periodo
enero
2004-diciembre
2008,
en
pacientes
de
primera
consulta
al
servicio
de
Endocrinología.
Resultados:
Se
analizaron
278
historias
reportando
una
prevalencia
de
hipotiroidismo
subclínico
del
36,3%.
No
se
encontró
asociación
entre
sexo
y
colesterol
ni
entre
sexo
y
lipoproteínas
de
baja
den-
sidad
(LDL);
sin
embargo,
sí
hubo
asociación
entre
sexo
y
dislipidemia,
así
como
entre
sexo
e
índice
de
masa
corporal
(IMC)
y
entre
sexo
y
TSH.
En
el
análisis
de
regresión
lineal
entre
LDL
y
TSH,
colesterol
y
TSH
e
IMC
y
TSH
se
encontró
una
asociación
significativa
para
cada
una
de
ellas
con
un
coeficiente
R2de
Pearson
de
0,80,
0,81
y
0,85
respectivamente.
Conclusiones:
Las
concentraciones
de
TSH
presentan
una
asociación
estadística
en
relación
con
los
valores
de
colesterol
total
y
LDL,
pero
no
constituye
un
buen
predictor
clínico
de
este
pro-
ceso,
razón
por
la
que
no
se
puede
establecer
un
punto
de
corte
tras
el
cual
iniciar
tratamiento
sustitutivo
para
así
prevenir
el
aparecimiento
de
dislipidemias.
©
2012
SEEN.
Publicado
por
Elsevier
España,
S.L.
Todos
los
derechos
reservados.
Introduction
Thyroid
hormone
deficiency
may
occur
as
clinical
or
subclini-
cal
hypothyroidism.
Clinical
hypothyroidism
is
characterized
by
increased
thyroid-stimulating
hormone
(TSH)
levels,
low
triiodothyronine
(T3)
and
thyroxine
(T4)
levels,
and
asso-
ciated
clinical
signs,
while
in
its
subclinical,
asymptomatic
form
(which
is
known
to
affect
6---17%
of
the
population),
elevated
TSH
levels
and
normal
free
T4
levels
are
found
and
its
etiology
is
sometimes
unclear.1 --- 4
The
role
of
thyroid
hormones
on
the
cardiovascu-
lar
system
is
crucial,
and
a
strong
association
has
been
found
between
thyroid
hormones
and
both
lipid
profile
and
atherosclerotic
disease
as
predictors
of
cardiovascular
risk.5,6
Studies
conducted
in
hypothyroid
patients
have
reported
high
levels
of
total
and
low
density
lipoprotein
(LDL)
choles-
terol
and
decreased
levels
of
high
density
lipoprotein
(HDL)
cholesterol
as
compared
to
euthyroid
controls.1,7---10
The
pathophysiological
mechanism
accounting
for
the
atherogenic
process
consists
of
a
decreased
affinity
of
LDL
for
its
receptors,
decreased
biliary
excretion
of
choles-
terol,
and
decreased
lipoprotein
lipase
activity,
resulting
in
the
prolongation
of
the
half-lives
of
total
and
LDL
cholesterol.1,11,12
It
should
be
borne
in
mind
that
cardiovascular
disease
is
the
leading
cause
of
disability
and
early
death
worldwide,
and
makes
a
substantial
contribution
to
the
high
costs
of
health
care.
Atherosclerosis
is
the
main
condition,
related
to
coronary
artery
disease
and
a
significant
increase
in
mor-
bidity
and
mortality.13---15
Dyslipidemia
is
one
of
the
five
significant
risk
factors
for
the
development
of
cardiovascular
diseases,16,17 and
hypothyroidism
is
the
second
leading
endocrinological
dis-
ease
causing
dyslipidemia
after
diabetes
mellitus.
Thyroid
function
screening
studies
in
populations
with
hypercholes-
terolemia
have
found
clinical
and
subclinical
hypothyroidism
in
2---9%
of
patients.14,18
It
should
also
be
noted
that
a
study
where
patients
were
distributed
into
groups
based
on
their
severity
of
dys-
lipidemia
found
the
greatest
proportion
of
patients
with
subclinical
hypothyroidism
in
the
group
with
the
highest
serum
cholesterol
levels,
which
confirmed
that
subclini-
cal
hypothyroidism
is
a
risk
factor
for
atherosclerosis
and
myocardial
infarction.11,19---25
The
Third
U.S.
National
Health
and
Nutrition
Examination
Survey
(NHANES
III)
showed
higher
cholesterol
and
LDL
levels
in
patients
with
subclinical
hypothyroidism
as
compared
to
euthyroid
patients,
but
after
adjustment
for
variables
such
as
sex,
race,
age,
and
the
concomitant
use
of
oral
lipid
low-
ering
drugs,
hypothyroidism
was
not
related
to
an
abnormal
lipid
profile.1,8,26
The
main
controversy
in
the
vast
majority
of
studies
on
the
adequate
time
to
start
hypothyroid
treatment
is
focused
on
the
TSH
cut-off
value
below
which
hormone
replacement
therapy
should
be
started
in
order
to
normalize
lipid
levels.
The
presence
or
absence
of
antibodies
and
the
risk-benefit
of
treatment
should
also
be
considered.11,27---30
The
purpose
of
this
study
was
to
establish
the
degree
of
clinical
and
statistical
association
of
TSH
levels
and
lipid
profile,
what
the
contribution
of
replacement
therapy
as
an
intervention
to
prevent
the
occurrence
of
dyslipidemia
would
be,
and
the
ideal
cut-off
point
for
starting
such
ther-
apy.
Subjects
and
methods
This
was
a
retrospective,
cross-sectional
study
enrolling
all
patients
attending
the
endocrinology
department
of
the

Relationship
of
TSH
levels
and
dyslipidemia:
Cut-off
point
to
start
replacement
therapy
577
Table
1
Diagnosis
in
relation
to
age
and
sex.
Clinical
hypothyroidism
N
=
112
Subclinical
hypothyroidism
N
=
101
Euthyroid
N
=
65
Total
N
=
278
Age
(years)
Med
(IQR)
53
(44---63)
53
(42---62)
46
(38---54)
53
(42---60)
Females
%
(95%
CI)
42.8
(36.3---49.5)
34.1
(27.9---40.6)
23
(17.8---29.2)
229
(100)
Males
%
(95%
CI)
28.6
(16.6---43.3)
49.6
(32.5---61.7)
24.5
(13.3---38.9)
49
(100)
CI:
confidence
interval;
IQR.
second
interquartile;
Med:
median.
General
Army
Hospital
No.
1
(also
known
as
HG-1
and
Quito
Military
Hospital)
with
suspected
subclinical
hypothyroidism
during
the
period
2004---2008.
Thyroid
hormone
and
lipid
pro-
file
tests
of
all
patients
were
requested
during
their
first
visit,
and
clinical
histories
from
patients
who
had
com-
plete
results
for
thyroid
function,
anthropometrics,
LDL
cholesterol,
and
total
cholesterol
were
also
selected
for
the
research.
Patients
attending
the
endocrinology
outpatient
clinic
whose
clinical
history
included
all
variables
proposed
in
the
case
report
form
were
considered
to
be
eligible,
while
patients
having
a
concurrent
disease
as
the
causative
fac-
tor
of
lipid
changes,
pregnant
women,
and
patients
already
receiving
lipid
lowering
treatment
before
being
diagnosed
with
hypothyroidism
were
excluded
from
the
study.
Data
were
collected
by
reviewing
clinical
histories.
These
mainly
consisted
of
progress
notes
of
the
first
visit
and
results
obtained
at
the
laboratory
of
the
Military
Hospital.
In
the
first
stage,
a
univariate
analysis
was
performed.
Continuous
variables
were
summarized
with
measures
of
central
tendency
and
dispersion.
Categorical
variables
were
summarized
using
frequencies
and
their
respective
95%
confidence
intervals.
In
the
second
stage,
a
bivariate
analysis
was
performed
to
determine
the
degree
of
association
of
TSH
with
LDL
cholesterol,
cholesterol,
and
body
mass
index
(BMI).
Linear
regression
with
Pearson’s
R2coefficient
was
used
for
this
purpose.
The
receiver
operating
characteristics
(ROC)
curve
was
used
to
measure
the
clinical
predictive
power
of
the
associ-
ation
between
TSH
and
dyslipidemia.
In
addition,
variables
that
included
the
age
groups
of
patients
over
and
under
50
years
of
age
and
a
variable
including
cholesterol
levels
higher
than
200
mg/dL
and/or
LDL
cholesterol
levels
higher
than
130
mg/dL
as
indicative
of
dyslipidemia
were
used.
Results
All
clinical
histories
from
patients
attending
the
endocrinol-
ogy
department
of
the
Military
Hospital
from
January
2005
to
December
2008
were
reviewed,
and
TSH
tests
were
requested.
There
were
805
clinical
histories
that
met
this
criterion.
Of
these,
130
clinical
histories
not
including
the
results
of
lipid
and
thyroid
profiles,
height
or
weight
were
excluded,
leaving
675
histories.
Exclusion
criteria,
as
reported
in
the
methodology,
were
met
by
397
clinical
his-
tories.
A
total
of
278
clinical
histories
were
therefore
used
for
the
final
analysis.
The
median
age
of
the
278
patients
was
51
years
(IQR
[second
interquartile]:
42---60),
and
female/male
ratio
was
4.67---1.
One
hundred
and
twelve
subjects
(40.3%
95%
CI
[95%
confidence
interval]:
34.5---46.3%)
had
a
diagnosis
of
clini-
cal
hypothyroidism;
101
(36.3%
[95%
CI:
30.7---42.3%])
had
a
diagnosis
of
subclinical
hypothyroidism;
and
65
(23.4%
[95%
CI
18.5---28.8%])
patients
were
euthyroid.
Median
age
was
similar
across
diagnoses
(Table
1).
Median
total
cholesterol
level
in
the
178
patients
was
212
mg/dL
(IQR:
194---240),
and
median
LDL
cholesterol
level
was
137
mg/dL
(IQR:
119---157).
As
regards
anthropometric
data,
median
height
was
154
cm
(IQR:
150---160)
and
median
weight
was
66
kg
(IQR:
59---73),
with
a
resulting
median
BMI
of
27.1
kg/m2(IQR:
24.9---29.9)
(Table
2,
Figs.
1
and
2).
Dyslipidemia
(according
to
the
criteria
given
in
the
sub-
jects
and
methods
section)
was
found
in
211
patients
(75.9%
[95%
CI;
70.4---80.8]),
with
a
mean
TSH
level
of
5.8
mU/L
(IQR
[4.8---7.2])
in
patients
with
subclinical
hypothyroidism.
A
1.2---1
ratio
was
seen
between
subjects
over
and
under
50
years
of
age.
No
significant
difference
was
found
in
sex
distribution
in
these
age
groups
(OR:
0.87
[95%
CI:
0.47---1.62]).
No
significant
difference
was
seen
either
in
TSH
levels
between
both
age
groups.
A
significant
differ-
ence
was
however
seen
in
total
and
LDL
cholesterol
levels
and
BMI,
with
higher
values
found
in
subjects
older
than
50
years
(Table
3).
No
association
was
found
between
sex
and
total
choles-
terol
or
between
sex
and
LDL
cholesterol.
However,
0
50
100
150
200
250
300
Clinical
hypothyroidism
Subclinical
hypothyroidism
TotalEuthyroidism
Total cholesterol mg/dL
Figure
1
Mean
total
cholesterol
levels
and
diagnosis.

578
V.
Sarzosa
Terán,
M.A.
Astudillo
Calle
Table
2
Diagnosis
in
relation
to
lipid
changes
and
anthropometric
values.
Clinical
hypothyroidism
N
=
112
Subclinical
hypothyroidism
N
=
101
Euthyroid
N
=
65
Total
N
=
278
Statistical
significance
Cholesterol,
mg/dL
Med
(IQR)
213
(189---245)
219
(199---247)
203
(180---230)
212
(194---240)
p
=
0.0055
LDL,
mg/dL
Med
(IQR)
139
(113---160)
142
(131---161)
126
(103---147)
137
(119---157)
p
=
0.0006
Height,
m
Med
(IQR) 1.53 (1.49---1.58) 1.56 (1.49---1.62)
1.55
(1.51---1.61)
1.54
(1.50---1.60)
p
=
0.073
Weight,
kg
Med
(IQR) 66 (59---72) 66 (58---73) 68 (62---76) 66 (59---73) p
=
0.209
BMI,
kg/m2
Med
(IQR)
27.8
(25.3---30.6)
26.1
(24.3---28.8)
27.55
(25.7---29.9)
27.1
(24.9---29.9)
p
=
0.035
TSH,
mIU/L
Med
(IQR) 6.73 (4.0---10.3)
5.8
(4.8---7.2)
2.51
(1.71---3.33)
5.1
(3.3---7.6)
p
=
0.000
IQR:
second
interquartile;
BMI:
body
mass
index;
Med:
median;
TSH:
thyroid-stimulating
hormone.
associations
were
seen
between
sex
and
dyslipidemia,
and
between
sex
and
BMI
and
sex
and
TSH
(Table
4).
Linear
regression
analysis
between
LDL
and
TSH,
choles-
terol
and
TSH,
and
BMI
and
TSH
showed
significant
associations
for
all
of
them,
with
Pearson’s
R2coefficients
of
0.80,
0.81,
and
0.85
respectively
(Figs.
3 --- 5 ).
Analysis
of
the
ROC
curve,
intended
to
test
the
discriminant
power
of
TSH
measurement
for
predicting
dys-
lipidemia,
provided
a
non-significant
area
under
the
curve
(AUC
=
0.52
[95%
CI:
0.5121---0.6632])
(Fig.
6).
Since
a
clinical
association
was
not
found
between
TSH
levels
and
lipid
profile
changes,
the
next
planned
step,
namely
the
determination
of
the
cut-off
point
for
TSH
beyond
which
treatment
would
be
started,
was
not
warranted.
Discussion
This
study
showed
a
statistical
association
between
TSH
lev-
els
and
lipid
profile
changes.
It
may
therefore
be
stated
Table
3
TSH
levels,
dyslipidemia,
and
body
mass
index
by
age
group.
Age
groups
Statistical
significance
<50
years
>50
years
TSH,
mIU/L
Med
(IQR) 4.93
(3.14---7.12)
5.37
(3.50---8.43)
p
=
0.17
LDL,
mg/dL
Med
(IQR)
130
(103---143)
143
(129---164)
p
=
0.000
Cholesterol,
mg/dL
Med
(IQR)
201
(175---223)
225
(203---250)
p
=
0.000
BMI,
kg/m2
Med
(IQR)
26.4
(24.5---28.8)
28.0
(25---31.2)
p
=
0.0015
IQR:
second
interquartile;
BMI:
body
mass
index;
LDL:
low
density
lipoprotein;
Med:
median;
TSH:
thyroid-stimulating
hormone.
Table
4
Total
cholesterol,
LDL,
and
TSH
levels
and
BMI
by
sex.
Males Females Statistical
significance
Cholesterol
mg/dL,
Med
(IQR)
207
(192---230)
213
(194---243)
p
=
0.267
LDL
mg/dL,
Med
(IQR)
134
(112---154)
139
(121---158)
p
=
0.316
BMI
kg/m2,
Med
(IIR)
25.95
(23.93---28.01)
27.35
(25.0---30.15)
p
=
0.0082
TSH
mIU/L,
Med
(IQR)
6.85
(3.81---8.77)
4.97
(3.33---7.08)
p
=
0.05
IQR:
second
interquartile;
BMI:
body
mass
index;
LDL:
low
density
lipoprotein;
Med:
median;
TSH:
thyroid-stimulating
hormone.

Relationship
of
TSH
levels
and
dyslipidemia:
Cut-off
point
to
start
replacement
therapy
579
LDL: low density lipoprotein
0
20
40
60
80
100
120
140
160
180
Clinical
hypothyroidism
Subclinical
hypothyroidism
TotalEuthyroidism
LDL mg/dL
Figure
2
Mean
LDL
cholesterol
levels
and
diagnosis.
R2=0.80
TSH
100
90
80
70
60
50
40
30
20
10
0
8060
TSH: thyroid-stimulating hormone
LDL: low density lipoprotein
100
120
140
160
LDL
180
200
220
240 260
Figure
3
Linear
regression
of
TSH-LDL
cholesterol.
R2=0.81
TSH
100
90
80
70
60
50
40
30
20
10
0
150
TSH: thyroid-stimulating hormone
250200
Total cholesterol
350300
Figure
4
Linear
regression
of
TSH-total
cholesterol.
R2=0.85
TSH
100
90
80
70
60
50
40
30
20
10
0
2015
BMI: body mass index
TSH: thyroid-stimulating hormone
40353025
BMI
45
Figure
5
Linear
regression
of
body
mass
index-TSH.
that
TSH
level
is
a
risk
factor
for
the
development
of
lipid
changes,
but
is
not
a
good
clinical
predictor
of
such
changes.
However,
this
association
has
no
clinical
implications
for
prediction,
as
it
is
shown
by
the
analysis
of
the
ROC
curve.
In
studies
on
clinical
predictors,
it
is
very
important
to
distinguish
between
the
existence
of
an
association
between
two
variables
and
the
strength
of
such
an
association
with
its
attendant
clinical
implications.
In
fact,
it
has
been
shown
that
in
many
studies
where
a
statistical
association
has
been
found
between
two
variables,
the
association
loses
pre-
dictive
power
when
it
is
converted
into
confirmatory
and
exclusionary
powers.
ROC curve
1.0
0.9
0.8
0.6
0.7
0.5
0.4
0.3
0.2
0.1
0.0
0.0
0.1
0.2
0.3
0.60.50.4
ROC curve: 0.52
1-Specificity
1.00.90.80.7
Sensitivity
Figure
6
Receiver
operating
characteristics
curve
for
the
dis-
criminant
power
of
TSH
in
dyslipidemia.

580
V.
Sarzosa
Terán,
M.A.
Astudillo
Calle
This
is
precisely
what
happened
in
this
study:
a
statisti-
cal
association
was
indeed
shown
between
dyslipidemia
and
altered
TSH
levels.
However,
the
strength
of
this
association
was
very
weak,
and
it
had
therefore
no
value
as
a
clinical
predictor.
This
was
the
reason
why
assessment
of
the
cut-off
point
made
no
sense.
It
should
be
noted
that
this
does
not
mean
that
TSH
is
no
longer
significant
as
a
risk
factor
for
dyslipidemia.
How-
ever,
it
should
be
used
for
primary
prevention,
not
for
taking
treatment
decisions.
It
is
significant
that
8
out
of
every
10
histories
reviewed
were
of
female
patients,
which
agrees
with
the
results
of
previous
studies.
It
should
be
stressed
that
the
study
was
conducted
at
the
Army
Hospital,
where
the
majority
of
patients
are
male.
This
confirms
the
predominance
of
thyroid
disease
in
females.
The
increasing
prevalence
of
subclinical
hypothyroidism
was
also
confirmed
by
the
higher
prevalence
rates
reported
in
patients
between
the
fifth
and
sixth
decades
of
life.
A
predominance
of
patients
with
clinical
hypothyroidism
was
also
found,
but
it
should
be
noted
that
the
highest
total
cholesterol
and
LDL
cholesterol
levels
were
seen
in
patients
with
subclinical
thyroid
disease
with
highly
significant
p
val-
ues,
in
whom
a
TSH
cut-off
value
of
5.8
mU/L
was
found.
These
figures
agree
with
the
results
of
other
studies
and
sug-
gest
that,
despite
the
low
predictive
power
for
dyslipidemia
of
TSH
discussed
in
prior
paragraphs,
lipid
profile
should
be
tested
in
patients
with
TSH
levels
higher
than
the
cut-off
point
found.
Mention
should
be
made
of
the
worldwide
controversy
about
the
relationship
between
subclinical
hypothyroidism
and
dyslipidemia.
Prevalence
rates
of
hypothyroidism
were
shown
to
be
7.5%
in
females
and
2.8%
in
males,
ranging
from
3%
to
15%
in
the
adult
population.
Dyslipidemia
is
one
of
the
five
risk
factors
for
the
devel-
opment
of
cardiovascular
disease,13 and
hypothyroidism
is
the
second
leading
endocrinological
disease
causing
dysli-
pidemia
after
diabetes
mellitus.
Thyroid
function
screening
studies
in
populations
with
hypercholesterolemia
found
clin-
ical
and
subclinical
hypothyroidism
in
2---9%
of
patients.14
Different
views
also
exist
regarding
screening
in
the
general
population.
The
American
Thyroid
Association
recommends
TSH
measurements
from
the
age
of
35
years
and
every
five
years
thereafter
in
asymptomatic
adults,
while
the
U.S.
Preventive
Services
Task
Force
questions
screening,
particularly
in
men,
who
have
a
much
lower
inci-
dence
of
subclinical
hypothyroidism
as
compared
to
older
women.
Their
main
argument,
however,
is
that
studies
do
not
lead
to
clear
conclusions
as
to
whether
early
treatment
does
or
does
not
decrease
morbidity
and
mortality
or
improves
quality
of
life
in
these
cases.
This
agrees
with
the
findings
reported
in
our
environment.4
Among
consensuses
reached
in
Latin
American
countries,
it
should
be
noted
that
the
Cuban
Consensus
on
Subclinical
Hypothyroidism
requires
a
TSH
level
higher
than
3.5
mU/L
and
normal
free
or
total
T4
levels
for
diagnosis
of
the
condi-
tion,
and
the
identification
of
positive
peroxidase
antibodies
before
treatment
is
started.4
Increased
levels
of
total
and
LDL
cholesterol
and
apolipoprotein
A,
a
highly
atherogenic
LDL
variant,
like
apo
B,
have
also
been
reported.
Studies
in
patients
with
hypothyroidism
showed
prolongation
of
the
half-life
of
LDL
cholesterol
due
to
decreased
catabolism,
an
effect
which
is
reversible
upon
the
administration
of
hormone
treatment.5,7
Additional
data
from
human
fibroblasts
confirm
that
T3
induces
an
increased
degradation
of
LDL
cholesterol,
which
is
a
direct
mediator
of
the
increase
in
the
number
of
LDL
receptors
with
no
change
in
LDL
affinity
for
these
receptors.1,8
Studies
have
shown
that
each
mmol/L
reduction
in
LDL
cholesterol
is
associated
with
a
19%
decrease
in
coronary
morbidity
and
mortality.
This
results
in
a
23%
reduction
in
myocardial
infarctions
and
coronary
deaths,
a
24%
reduc-
tion
in
the
coronary
revascularizations
required,
and
a
17%
reduction
in
fatal
and
nonfatal
stroke,
with
a
21%
overall
reduction
in
cardiovascular
events.15
The
NHANES
III
survey
of
17,353
US
patients
showed
high
TSH
levels
consistent
with
hypothyroidism
in
4.6%,
and
noted
that
such
levels
were
more
common
in
women
with
low
birthweight
and
low
BMI
in
childhood,26 data
which
should
be
investigated
in
future
studies
in
our
country.
Research
on
patients
with
hypothyroidism
showed
an
increase
in
LDL
cholesterol
half-life
secondary
to
decreased
catabolism,
an
effect
that
is
reversible
with
replacement
therapy.
It
needs
therefore
to
be
confirmed
whether
or
not
LDL
cholesterol
levels
decrease
when
replacement
therapy
is
started
with
levothyroxine
despite
the
absence
of
lipid
lowering
treatment.14
Levothyroxine
sodium
should
also
be
prescribed
at
the
doses
required
to
normalize
TSH
in
the
presence
of
positive
antibodies,
dyslipidemia,
or
TSH
levels
higher
than
10
mU/L
or
gradually
increasing.4
This
study
is
the
first
retrospective
research
conducted
in
our
country
to
assess
the
association
between
subclinical
hypothyroidism
and
lipid
profile.
It
provides
data
about
TSH
levels
that
cause
lipid
changes
in
our
environment,
although
it
should
be
borne
in
mind
that
they
are
not
the
best
predic-
tor
for
the
occurrence
of
such
changes.
It
is
also
expected
to
be
the
basis
for
future
prospective
studies.
One
of
the
limitations
of
this
study
was
its
retrospec-
tive
nature.
In
addition,
data
for
the
clinical
histories
were
recorded
by
other
people.
It
should
be
stressed
that
many
medical
charts
were
excluded
from
the
study
because
they
did
not
include
the
data
required
for
the
analysis.
A
sig-
nificant
disadvantage
that
should
be
mentioned
is
the
lack
of
lipid
profile
results
in
patients
diagnosed
with
subclinical
hypothyroidism,
probably
because
of
a
lack
of
awareness
about
the
correlation
between
the
disease
investigated
and
dyslipidemia.
A
bias
that
should
be
taken
into
account
is
that
a
majority
of
the
study
population
from
the
Military
Hospital
belonged
to
the
middle
and
upper
middle
classes,
and
the
study
results
can
therefore
only
be
extrapolated
to
populations
with
the
same
socioeconomic
characteristics.
This
research,
which
was
conducted
in
order
to
find
an
association
between
TSH
levels
and
lipid
profile
changes,
will
serve
as
the
basis
for
future
prospective
research
where
long-term
monitoring
of
patients
may
allow
for
analyzing
parameters
that
could
not
be
studied
in
a
retrospective
study
such
as
this.
It
will
also
be
appropriate
to
consider
studies
that
allow
for
establishing
the
prevalence
of
cardiovascular
risk
fac-
tors
in
relation
to
subclinical
hypothyroidism,
with
regard

Relationship
of
TSH
levels
and
dyslipidemia:
Cut-off
point
to
start
replacement
therapy
581
to
blood
pressure
levels,
cardiac
muscle
hypertrophy,
the
size
of
atheromatous
plaque
at
the
aortic
level,
the
devel-
opment
of
peripheral
neuropathy,
and
the
influence
of
associated
factors
such
as
smoking
and
diabetes
mellitus,
taking
into
account
that
subclinical
hypothyroidism
is
a
marker
of
nephropathy
and
coronary
artery
disease
in
dia-
betic
patients.
The
clinical
implications
of
this
study
are
very
impor-
tant,
because
it
helps
us
to
understand
the
true
value
of
TSH
measurements
in
patients
with
suspected
subclinical
hypothyroidism.
In
fact,
based
on
the
results
obtained,
there
would
appear
to
be
no
point
in
using
TSH
levels
when
making
the
decision
whether
or
not
to
start
replacement
therapy
to
prevent
dyslipidemia.
Funding
The
study
was
fully
financed
by
the
authors.
Conflicts
of
interest
The
authors
state
that
they
have
no
conflicts
of
interest.
MA
and
VS
are
specialists
in
internal
medicine
(Instituto
Superior
de
Postgrado-Facultad
de
Ciencias
Médicas-
Universidad
Central
del
Ecuador
[ISP-FCM-UCE]).
This
research
was
conducted
in
the
setting
of
activities
related
to
their
degree
dissertations.
Acknowledgements
We
thank
doctors
Rodrigo
Rovayo
P.
and
Juan
Moreira
for
their
cooperation
in
the
scientific
and
methodological
con-
duct
of
the
study.
We
also
thank
the
General
Army
Hospital
No.
1.
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