Download Physiological variations in thyroid hormones: physiological and

Clinical C’hemistiy 42:1
135-139
(1996)
Physiological
variations
in thyroid
physiological
and pathophysiological
A.
DELBERT
Thyroid
hormone
thyrotropin
(TSH)
mone
secretion
active
triiodothyronine
sues
via
both
serious
the
events
onset
of
sleep
noon
hours.
±50%.
and
nadir
Peak
and
nadir
concentrations
effect
on
circulating
T4
The
is
not
T4
significant
on
thyroid
for
variation
concentrations
of
TSH
decreased
cretion
ratio,
and
concentrations.
hormone
in
iodine
T4
production,
an
increased
Excessive
biosynthesis
biosynthetic
increased
an
ratio
by inhibiting
the
resulting
goiter,
can
in-
All
hormones
in
T4 secretion,
conjugates,
and
application
at the
TERMS:
hormone
regulation
Nichols
July
thyrotropin
Institute,
3!,
most
of FT4.
The
latter
variations.
Other
measurements
TBG,
and thyroglobulin.
or no clinical
important
use include
uptake
and
little
blood.
glucuronide
in vitro
TSH
and
include
a direct
the T3 resin
include
T3,
free
T3
is chronic.
#{149}
triiodothyronine
.
thyroxine.
San Juan
Capistrano,
CA
92690.
Fax 714-728-
4960.
Received
clinical
and
have
The
measurement
1995;
accepted
October
13, 1995.
135
VARIATIONS
There
are
evident
in all of the in vitro
These
variations
Nonstandard
Corning
sulfate
acid
time.
only
in peripheral
the
or indirect
PHYSIOLOGICAL
INDEXING
present
thyroacetic
metabolites,
bioactivity.
be measured
triiodothyroacetic
III MDI
sulfoconjugated,
to the
Of all the
for
T4 also
by a type
deaminated
of TRH,
for routine
(VT3), rT3,
hypothyroidism
can
T3
tissue.
be
of
monodeio-
produces
(ri’3)
can
manifest
iodothy-
II [2]. Most
adipose
T3
(or)
acid
measurements
measurements
thyroid
involved
of the
II MDI
derivatives.
triiodothyroacetic
However,
se-
and
acid
tissues,
via hepatic
T4
albumin
by the
type
I and
brown
and
The
peripheral
to T3
Type
“reverse”
and
to
type
and
tissues,
conjugated,
and
(prealbumin)
I MDI.
to inactive
nonhepatic
prohormone
in serum.
is thyroxine-binding
to be derived
pituitary,
thyropropionic
T3
T3/T4
block
enzymes
and
and
iodine
T3f1’4
circulating
in reduced
concentrations,
excess
with
most
glucuronide
im-
thyroid
increased
intake
in
of the
is distributed
appears
triiodothyrespectively.
proteins
by deiodination
in brain,
is deiodinated
Subthreshold
associated
of
body
T4
by type
of T4
action
hormone
proteins
whereby
hypothalamic
production,
secretion
(MDIs)
T
active
to binding
binding
monodeiodinases
local
and
pituitary
loop
and
is
secreted
to stimulate
TRH
transthyretin
roles.
circulating
dination
no
ambulatory
a minimal
intake.
are
the
is
of these
it is metabolized
ronine
the
geographic
has
increased
iodine
process,
TSH
iodine
iodine
goiter,
or
significant
also
intake
secretion,
uptake,
no
Nutrition
of
training,
exercise,
and
size
there
physical
by
synthesis
but
the
and
(TSH)
in turn
(TRH)
the pituitary
to
TSH
bound
(TBG),
secretion
system
at both
it is converted
secondary
where
acts
the
thyrotropin
by a feedback-inhibiting
to inhibit
important
play
after-
(VT’4)
by
[1].’TSH
thyroliberin
vascular
and
circulates
globulin
concentra-
large
subjects
which
most
at the
portal
stimulates
T4,
is a cirthe
T3
TSH
and
differ
and
the
weight,
function,
variation.
except
of
metof little
values
during
healthy
immobilization,
environmental
creased
In
of body
posture,
Status
because
pool.
impact
habitus,
concentrations
significant
extrathyroidal
(T3)]
gland
by hypothalamic
release,
[where
estrogens
peak
thyroxine
is regulated
pituitary
pituitary
TSH
ronine
There
with
iodo-
the
levels
are
pregnancy.
into
gland
at
cancer,
secretion,
of
function
the
regulated
in
infection,
during
of TSH
from
Control
differences
of placental
gland
secretion
modified
gender
effects
Thyroid
free
(trauma,
and
for the
and
FISHER
largely
tis-
of the
systems.
regulated
illness
prohor-
regulation
activities
enzyme
gonadotropin
rhythm
and
pituitary
in peripheral
influencing
Racial
except
chorionic
cadian
gland
production
is developmentally
significance
tions
thyroid
(T)
diseases).
if the
via
(T4)
nonthyroidal
abolic
the
regulated
thyroxine
monodeiodinase
levels
pact
is
of
by
metabolic
thyronine
production
modulation
hormones:
considerations
marked
WITH
variations
are
in
hormone
abbreviations:
TSII,
thyroxine;
-F,.
thyronine
anonodeiodinase;
ri,,
and
human
gonadotropin.
hCG,
chorionic
and
summarized
triiodothvronine;
GENDER,
thyroid
tuG,
reverse
in
RACE,
protein
Table
thyrotropin;
FT.,
Thyroid
thyroliherin;
globulin;
FF,),
age,
measurements.
TRH,
(or
AGE
with
1 [3-6].
thyroxine-binding
F,;
AND
function
free
T4,
MDI,
14 (or
jodofree
T,);
136
NACB
Table
1. Changes
in thyroid-function
Serum
T4, nmol/L
FT4.
pmoi/L
Symposium
TBG,
mg/I
TSH, miIJ/L
indicators
with
age.a
conc
rT3,
nmol/L
T3, nmol/I
Tg, eg/L
T4 utilization,
per day
pg/kg
Fetus
12-20
weeks
5-50
0-50
1-8
2-23
21-30
weeks
35-100
5-12
1.9-8.8
8-33
0.10-0.75
31-40
weeks
70-180
12-22
3-12
15-50
0.2-1.5
22-42
0.5
-
1
-
6-230
2
2-54
5
-
1.5-7.7
Infant
1-4
days
142-277
28-68
1-39
1-4
weeks
106-221
12-30
1.7-9.1
76-210
10-23
0.8-8.2
16-36
1.6-3.8
1-12
months
-
2-110
0.4-4.5
-
7
0.17-2.0
-
6
1.5-11.4
1.6-5.3
10
Child
1-5
years
94-193
10-27
0.7-5.7
12-28
1.6-4.1
0.23-1.1
2-65
5
82-171
13-27
0.7-5.7
12-28
1.4-3.7
0.26-1.2
2-65
4
years
71-151
10-26
0.7-5.7
14-30
1.3-3.3
0.29-1.3
2-36
3
years
54-152
10-26
0.7-5.7
14-30
1.2-3.2
0.39-1.2
2-36
2
21-50
years
55-161
12-32
0.4-4.2
17-36
1.1-3.1
0.46-1.2
2-25
1.5
51-80
years
55-160
12-32
0.4-4.2
17-36
0.6-2.8
0.46-1.2
2-25
1.5
clearance;
androgens
6-10
years
11-15
16-20
Adult
4Data
from
Values
refs. 3-6
Corning
in the
thyroid
hormone
weight)
fetus
in early
all
utilization
and
Clinical
Correlations
highest
rates
decrease
Division.
of progressive
function,
changes
on
tions
is minimal.
age after
In adults
in serum
decreases
in
>50
years,
subjects
T4
T4
is a modest,
studies
general,
little
tion.
Estrogen
hancing
little
or
no
the
and
hormonal
changes
significant
increases
serum
sialylation
of
in
gender
TBG
the
manifest
other
20
DIETARY
FT4,
or
Caloric
restriction
T3
and
T4
at both
the
net
TSH
are
a
2. Changes
Decreased
TRH
secretion
Decreased
TSH
response
Decreased
pituitary
Decreased
T4 secretion
Decreased
T4 disposal
effect
TSH
of
Basal
and
(slight)
Decreased
T3 disposal
No change
in serum
(slight)
aFrom ref. 7.
feedback
somewhat
tissues
are
These
of
puberty
healthy
or
FT4
and
TSH,
serum
T4
T3
administration
or
(contra-
during
[5].
subjects
racial
varia-
pregnancy
which
by
en-
reduces
suppression
TSH
not
Somatostatin
reverse
function
with aging.a
with
caloric
CIRCADIAN
sensitivity
There
and
in
release.
usually
AND
SEASONAL
is a clear
the
daytime,
before
sleep
f9-1l/.
and
increase
Amounts
of
concentrations
in 98
healthy
8) and
decline
and
TRH
fasting
is
in rats,
does
not
[8/. T4 and
FT4
in association
of healthy
one
older
in circulating
in humans.
studies
=
the
deprivation
significantly
variation
3 summarizes
n
the
RHYTHMS
circadian
in animals
cohorts
altered
to
mediating
deprivation.
during
two
as in anorexia
the
tone,
during
[8].
of the caloric
contribute
abolishes
in TSH
are not
duration
to caloric
somatostatin
decline
in T4-to-T3
concentrations
mechanism(s)
antibody
are
reduction
may
in response
levels.
in peripheral
restriction,
The
effects
activities
and
secretion
with
tissue
concentrations
T3
prolonged
secretion
acute
serum
to the extent
increased
the
TSH
I MDI
in
cortisol
decreased
peripheral
a concomitant
are related
of TSH
suggesting
type
the
with
function,
and
a reduction
increased
clear.
thyroid
serum
In severe
nervosa,
to reduce
and
reduced,
effects
trations
T4 monodeiodination
TBG
pharma-
NUTRITION
tends
TRH-stimulated
conversion
in
or
concentrations
molecule,
to TRH
(negative)
Decreased
Decreased
in thyroid
circulating
predominantly
drug
uses)
hypothalamic-pituitary
concentrations
Table
are
during
therapeutic
INFLUENCES,
reduced
concentradecrease
in serum
indicators
clinically
hepatic
or
T4,
there
progressive
variation
thyroid-function
show
effects
ceptive
deprivation.
show
during
concentrations
cologic
reduce
these
birth
T3 concentrations.
Recent
[2]. However,
ages
thyroid
2 [7]. The
thyroid
There
with
age
in Table
circulating
concentrations
TSH
are
in hypothalamic-pituitary
as summarized
these
serum
modest
changes
metabolic
of
women.
modestly.
with
[7]. In
and
as
of
rate.
more
but
observed
levels
kilogram
period,
progressively
are no changes
are
(per
this
production
there
utilization
variety
during
decrease
concentrations,
to maximum
utilization
[3, 4]. T4, T3, VT4, FT5,
infancy
are
indicators
to 50 years
TSH
and
presumably
T4 utilization
/6,1; other
In
Institute
progressively
matures
production
concentrations
axis
Nichols
are 2 SD range.
function
body
and
TSH
in the
evening,
decline
slowly
mean,
adults,
(67-84
children,
sleep.
peak
serum
ages
5-18
n
group
=
concenare
peak
during
younger
years,
and
and
nadir,
one
TSH
concentrations
years,
(20-27
8) [9-11].
low
shortly
Table
TSH
and
in
years,
TSH
is
Clinical
Table
3. Circ adian
variation
TSR conc,
in serum
mlU/L
Chemistry
Mean
W
Children,
98
5-18
1, 1996
lutropin
TSH.a
(±SD)
and
Time
Nadir
Nadir
Peak
during
3.7
1500
2300
may
1.6
(±1.0)
(±2.0)
8
1.4
(±0.4)
0.9
(±0.3)
1.94
(±0.5)
1653
0356
Adults,
67-84
8
1.01
(±0.7)
0.73
(±0.6)
1.30
(±0.9)
1611
0215
refs.
Thus,
and
the
tration
[15].
of
because
secreted
in
nocturnal
a pulsatile
TSH
quency
and
and
basal
rhythm,
tyrapone
TSH
not
increment
TSH
stress,
of the
is
of the
the
circadian
f8].
in nonthyroidal
illness,
syndromes
states,
and
TSH
with
The
serum
TSH
0900
concentration.
and
1600
circadian
usually
variation
serum
However,
does
in TSH
T4 concentrations,
represents
(500-600
exceed
has
small
the hourly
fraction
approximates
the measured
variation
between
19-11].
The
a minimal
effect
T4 secretion
rate
of the extrathyroidal
change
lution,
but
known
there
is
There
concentrations,
with
vs summer,
variation
peripheral
variation
in plasma
concentration.
winter
no
There
values
for serum
significant
this
be
on
(3-5
T4 pool
higher
to an effect
no data
TSH
with
due
to hemodi-
change
maintain
normal
increased
T4
concentration
in
during
to suggest
the
that
be seasonally
the
CYCLE,
is some
gens
reduce
of -300
tg
trimester.
fetal
T4
sex-related
TSH
increase
TBG.
are
and
The
effects
in the
/8].
in
when
cycles
tend
estrogens
in the
production
as already
in
phase
tend
excessive
related
to
men
and
to have
obtundation
andro-
estrogens
there
to exogenous
irregular,
bleeding
of
the
in
TBG
during
some
the
maternal-toT4
maternal
within
the
some
is maximal
turnover
normal
large
bioactivity.
the
end
the
time
of
increase
a transient
range
produces
near
At
is a transient
(or)
the
placenta
TSH-like
it declines.
and
hCG
of the
hCG
in maternal
decrease
first
peak
serum
in serum
TSH
/15/.
IMMOBILIZATION,
hormonal
EXERCISE,
response
of
TRH
/16,
lin
release,
the
icance
cycle
[13].
testing.
anovulatory
influence
[14/.
habitus,
ovulatory
on
prolactin,
AMBULATORY
of
the
and
thyroid
corticotropin
have
thyroid
in the
endocrine
little
impact
with
function
absence
function.
of
TSH
cortisol
regard
and
insu-
secretion.
nutrition,
are
are
secre-
inhibits
to training,
axis aspects
posture,
possibly
responses
thyroid
symnpa-
corticotropin,
increases
The
Immobilization,
increased
secretion
is related
all of the
training.
and
epinephrine
changes
these
involves
somatotropin,
vasopressin,
increased
and
of health;
exercise
to exercise
increased
17]. The
extent
state
during
These
activity,
tion
The
amount
greater
placenta
concentrations
concentrations
the
in
is transient
remain
has
which
concentrations
to
for
increase
of T4,
increase
are
pregnancy
in the extrathyroidal
increase
However,
which
by the
f3-endorphin,
variation
discussed,
of the menstrual
menstrual
an
and
diurnal
an
magnitude
reason
The
in
STATUS
is no apparent
the circulating
prolactin
luteal
and
of the
to reduce
and
increase
this
than
pregnancy
[15/.
women.
after
The
clear.
concentrations
of hCG,
POSTURE,
altered.
hut there
magnitude
than
hypothyroid,
can
to TRH,
of TSH
women
than
appear
TSH
pregnant
in most
lower
during
the
(hCG)
during
of this
degradation
involved
thoadrenal
Additionally,
responses
greater
menstrual
that
response
androgens
preovulatory
Women,
evidence
difference
in serum
are
are
hypothyroidism
but
and
transfer,
probably
FT4
of T4,
Placental
with
gonadotropin
an increase
14
concentrations
in the T4 dosage
with
12 to
in serum
coincident
increases
is not
in
in its
after
FT4
they
of
increase
winter
normative
PREGNANCY
the TSH
utilization
first
concentraas a result
increases
concentrations.
pool
trimester,
/8, 11, 12].
to accelerate
hormone
or T4 should
TSH
TSH
may
enlargement
increase
trimester,
however,
with
is associated
living
day)
Serum
parallel
T4 utilization
concentration
women
trimester
chorionic
general,
increases
in women
The
There
and
necessary
amounts
FT4
in
is minimal
of cold
at present
the
in
variation
T4
too,
of thyroid
are
amount
diurnal
a seasonal
variation,
be due
T4
concentration
a statistically
but
metabolism
months.
in total
protein
may
may
MENSTRUAL
In
Serum
and
Serum
first
and
fetus.
per
plateaus
are
human
controls.
by 2 5-50%,
there
the
in
and
tg
estrogen-stimulated
concentrations.
during
rate
to the
[15].
first
concentration
and
T3
nonpregnant
an
TBG
peak
Serum
is the
diurnal
and
concentrations.
controlled
The
slightly
hyperthy-
poorly
10%
T4
increase
pg).
There
This
not
secretion
since
a very
the
[IS].
increases
by an estrogen-induced
and
of pregnancy,
first-trimester
mellitus.
mediated
concen-
iodide
deficiency
the
in circu-
TBG
filtration
pregnancy
during
of TBG
of
(<50
iodine
concentrations
on
decrease,
intake
during
increase
clearance
nocturnal
hypercorti-
gland
of TBG
weeks
iodide
are
indicators
change
transfer
iodine
or relative
thyroid
tions
total
me-
of
in TSH
concentration
time of day may influence
absolute
synthesis
can
rhythm
marginal
sialylation
night,
iodothyronine
of inorganic
of
reduced
or delayed
part
rhythln
depressive
fre-
of glucocorticoids
diurnal
hypothyroidisln,
The
diurnal
variation
±50%
(Table
3), so that
tg)
the
manifest
suprachiasmatic
or early
abolish
cortisol
is obtunded
surgical
diabetes
and
the
alter
central
solism,
late
pulse
the
rhythm
be advanced
doses
secretion
preventing
does
roidism,
in the
and
TSH
in the
can
Pharmacologic
TSH
but
rhythm
day,
increased
diurnal
pacemaker
to light
[11/.
the
with
The
circadian
h by exposure
inhibit
is associated
circadian
the
respectively
throughout
amplitude.
by the
nucleus,
1-2
surge
pulse
modulated
fashion
clearance
glomerular
and
T4
effect
the
in
of iodide
areas
Total
transient
renal
increase
there
function
cycle.
the
of gonadal
systems,
of the
and
women,
an
concentrations
in
because
concentrations
pregnant
are interactions
endocrine
in thyroid-
menstrual
slightly
estrogen
these
variations
normal
lating
there
across
transient
fluctuate
In
although
hormones
because
9-10.
137
surge.
thyroid
Peak
2.4
(±1.0)
Adults,
20-27
from
No.
minimal
Study group and
age, years
“Data
42,
and
reduced
of limited
by
signif-
to thyroid-function
ambulatory
significantly.
Body
malnutrition,
also
status
weight
are
without
do not
and
body
effect
138
NACB
GEOGRAPHIC
The
AND
ENVIRONMENTAL
geographic
function
and
include
earlier,
the
iodine
detectable
in large
necessary
to
testing.
also
concentrations
but,
these
again,
areas
in
minor
circulating
associated
iodine
an increased
serum
T/F4
concentration
concentrations,
ratio,
iodine-deficient
in adults),
there
is an increased
hypothyroidism,
“euthyroid
increased
thyroid
decreased
total
and
are
reduction
in mean
can
thyroid
block
zymes
involved
effect)
[19].
reduced
and
in the
The
T4
population
and
inversely
related
[18/.
result
hypothyroidism
if the
iodine
likely
to produce
these
infants
are most
susceptible)
due to
variation
stuffs
individual
related
such
intake
with
subclinical
individuals
borderline
iodine
prevailing
amount
thyroid
gland
until
phenomenon,
NONTHYROIDAL
Systemic
are
and
chronic
variable
with
are
is some
food-
with
factor
and
secretion,
produce
iodine
a hyperthyroid
Graves
[20].
intake
is not
In
sufficient
iodine
state
disease
such
is such
the increased
of TBG
states,
referred
a variety
probabie
of
the
to
produce
substrate
in
contribute
The
thyroid
illness
are
the
patients
effects,
and
on the
underlying
infants
0-6
0-12
Children
months
1-10
Adolescents/adults
“From
ref.
be
seen-
or decreased
these
related,
thyroid
at least
T4
have
been
and
significantly
generally
pathogenetic
as
with
secondary,
euthyroid.
gene
glucocorticoid
associated
considered
remain
to reduce
hepatic
and
to
necrosis
shown
inhibit
dysfunctions
system
in part,
tumor
deprivation
Caloric
may
non-
adaptive
Treatment
is focused
disease.
SURGERY,
TRAUMA
trauma,
the
ations
in thyroid-function
those
seen
excessive
overt
is uncommon.
in
dietary
safe
intakes
illnesses,
thyroid
including
surgery,
is similar,
although
be
rapid
more
the
whether
syndrome
associated
T
is associated
The
medical
illness
process
[20-24].
determine
also
indicators.
in nonthyroidal
is more
with
changes
and
are
the
recovery
may
studies
are
ongoing
replacement
therapy
in
the
with
trauma
or surgery
to
pathogenesis
and
acute
alter-
similar
Experimental
may
to
low-T3
be beneficial.
are
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en-
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iodine
a
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serum
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free
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low
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by
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moribund
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Excessive
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T4,
in patients
efficiency
increased
and
trast
cretinism,
duration
a
with
recover
of the
extent
and
subjects
patients
led to designation
The
rT3,
in most
(as
to
of T4
is associated
in most
disorder
reductions
care
and
process
is reduced
secretion,
total
intensive
intake/day
biosynthesis
biosynthetic
in
amounts
and
be associated
and
a
have
of
which
FT4
related
conversion
clearance
T4,
normal
syndrome.”
are
reduced
concentrations
of the
illness)
sick
but
and
increased
TSH.
reduced
TSH
nature
.tg of iodine
hypothyroid
IQ
hormone
can
T4
and
total
or
metabolism
activity,
for
serum
normal,
serum
hormone
TBG
total
FT4
to the severity
FT4
concentrations,
(<50
and
acute
their
reduced
prevalence
neurological
transient
of alter-
changes
areas
the
include
degree
to the prevailing
iodine
intake.
Recommended
of iodine
intake
are shown
in Table
4 /6].
In severe
normal
low
or
I MDI
of
serum
The
(c) low,
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affinity
a variety
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normal
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in thyroid
of type
in
with
TSH
These
T3
reduced
in geographic
ratio,
(
and
decreased
These
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serum
[18/.
areas,
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T3/T4
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to goiter
geographic
to
include:
serum
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an inhibition
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inorganic
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in normative
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It is not
20]. These
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