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Interrelationships Among Cortisol, 17-Hydroxyprogesterone, and Androstenendione Exposures in the Management of Children With Congenital Adrenal Hyperplasia.
[congenital adrenal hyperplasia]
:
Hydrocortisone
is
the
standard
replacement
therapy
for
children
with
congenital
adrenal
hyperplasia
(
CAH
)
.
Relationships
between
cortisol
exposures
and
pharmacodynamic
responses
of
17
-
hydroxyprogesterone
and
androstenedione
exposures
have
not
been
systematically
evaluated
.
(
1
)
Assess
individual
oral
hydrocortisone
pharmacokinetics
;
(
2
)
relate
the
observed
cortisol
exposure
in
each
subject
to
the
observed
exposures
of
17
-
hydroxyprogesterone
and
androstenedione
;
(
3
)
determine
potential
individualized
treatment
regimens
based
on
each
subject
's
pharmacokinetic
and
pharmacodynamic
parameters
.
Thirty
-
four
patients
(
18
boys
,
16
girls
,
aged
1
.
4
to
18
.
1
years
)
with
CAH
underwent
6
-
hour
pharmacokinetic
studies
.
Results
were
analyzed
by
noncompartmental
methods
to
obtain
the
area
under
the
curve
(
AUC
)
for
cortisol
,
17
-
hydroxyprogesterone
,
and
androstenedione
;
maximum
concentration
and
time-
to
-maximum
concentration
for
cortisol
;
and
minimum
and
time-
to
-minimum
concentration
for
17
-
hydroxyprogesterone
and
androstenedione
.
Mean
(
SD
)
cortisol
half
-life
and
Cmax
were
1
.
01
(
0
.
20
)
hours
and
24
.
4
(
5
.
4
)
μg
/
dL
,
respectively
.
The
AUCs
for
cortisol
,
17
-
hydroxyprogesterone
and
androstenedione
were
40
.
8
(
14
.
5
)
μg
hour
/
dL
,
29
,
490
(
23
,
539
)
ng
hour
/
dL
,
and
680
(
795
)
ng
hour
/
dL
,
respectively
.
No
significant
relationships
existed
between
cortisol
AUCs
and
the
AUCs
of
either
17
-
hydroxyprogesterone
(
P
=
0
.
32
)
or
androstenedione
(
P
=
0
.
99
)
;
nor
were
there
differences
between
the
change
-from-baseline
concentrations
for
cortisol
with
either
17
-
hydroxyprogesterone
(
P
=
0
.
80
)
or
androstenedione
(
P
=
0
.
40
)
.
Cortisol
simulations
indicated
that
although
four
daily
doses
decreased
24
-
hour
hypercortisolemia
and
hypocortisolemia
,
substantial
periods
of
each
remained
.
Concentration
profiles
of
cortisol
,
17
-
hydroxyprogesterone
,
and
androstenedione
are
highly
variable
in
children
with
CAH
,
and
knowledge
of
them
can
assist
in
personalizing
the
therapy
of
CAH
patients
.
Hydrocortisone
's
rapid
half
-life
and
the
lack
of
a
sustained-released
product
make
it
difficult
to
closely
approximate
normal
circadian
profiles
.
Diseases
Validation
Diseases presenting
"closely approximate normal circadian profiles"
symptom
congenital adrenal hyperplasia
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