Trilostane

Trilostane,
a
competitive
inhibitor
of
3beta-hydroxysteroid
dehydrogenase,
has
been
successfully
used
to
treat
cats
with
HAC.8,9
Of
20
cats
in
two
series,
17
survived
for
more
than
3
months
and
many
survived
more
than
1
year.
This
is
much
better
than
with
any
other
medical
treatment.
There
have
been
no
pharmacokinetic
studies
of
trilostane
or
its
metabolites
in
cats;
however,
on
the
basis
of
one
case
in
which
cortisol
was
measured
sequentially,
it
would
appear
that
the
effect
on
cortisol
production
is
rapid
and
its
duration
of
action
is
<12
hours.8
Manufacturers
do
not
recommend
trilostane
be
used
if
concurrent
hepatic
or
renal
disease
is
present.
Trilostane
should
be
given
at
a
starting
dosage
of
1-2 mg/kg
PO
q
24 h.
However,
it
would
seem
logical
to
give
trilostane
at
the
same
frequency
as
insulin.
If
insulin
and
trilostane
are
being
used
twice
daily,
the
trilostane
dose
should
also
be
divided,
given
at
a
dosage
of
0.5-1 mg/kg
PO
q
12 h.
Reformulation
is
often
necessary.
Trilostane
seems
to
be
well-tolerated
and
improvement
is
often
noted
within
weeks.9
In
a
series
of
9
cats
with
HAC
and
DM
treated
with
trilostane,
insulin
dosage
requirements
decreased
by
36%
on
average
in
6
cats.
One
cat
had
an
insulin
dosage
requirement
increase.
DM
remission
did
not
occur.9
Important
possible
complications
of
trilostane
include
anorexia,
lethargy,
hyponatremia
and/or
hyperkalemia.
There
are
no
published
criteria
critically
evaluating
any
method
to
monitor
treatment
response.
Although
the
ACTHST
is
often
used,
target
cortisol
concentrations
and
test
timing
have
been
extrapolated
from
dogs.
However,
cats
have
been
successfully
treated
with
trilostane
using
these
extrapolated
values.8,9
In
general,
the
target
is
a
post-ACTHST
cortisol
concentration,
4
hours
after
trilostane
dosing,
>40 nmol/L
(>1.4 mcg/dL)
and
below
about
140 nmol/L
(5 mcg/dL).
However,
ACTHST
results
have
now
been
shown
to
be
unreliable
predictors
of
clinical
status
in
dogs
with
HAC
being
treated
with
trilostane.
Therefore,
it
is
recommended
to
closely
monitor
history
and
physical
examination
as
critical
parameters
during
treatment.

Other Medical Options

Mitotane
(o,p'-DDD,
Lysodren)
appears
to
be
well
tolerated
by
cats
despite
their
sensitivity
to
chlorinated
hydrocarbons.11
However,
mitotane
is
frequently
ineffective
in
controlling
clinical
signs
of
feline
HAC
in
cats.3
One
reported
case
given
50 mg/kg/day
PO
for
1
week
then
50 mg/kg/wk
PO
was
well
controlled
for
40
weeks
before
developing
signs
compatible
with
hypoadrenocorticism.12
If
trilostane
and
mitotane
are
unavailable
or
ineffective,
other
steroid
synthesis
inhibitors
may
be
used.
Metyrapone,
an
inhibitor
of
the
11beta-hydroxylase
enzyme
that
converts
11-deoxycortisol
to
cortisol,
proved
effective
at
least
transiently
in
controlling
clinical
signs
and
suppressing
cortisol
production
in
one
cat
(65 mg/kg
PO
q
12 h).14
Whether
long-term
therapy
with
metyrapone
can
control
feline
HAC
or
whether
rising
ACTH
concentrations
eventually
break
the
blockade
has
not
been
determined.
It
would,
however,
appear
to
be
potentially
useful
for
presurgical
stabilization.13
Ketoconazole,
an
antifungal
imidazole,
is
an
inhibitor
of
steroidogenesis
in
humans
and
dogs,
but
is
ineffective
in
cats.
Its
safety
has
been
questioned
because
anorexia,
weight
loss,
vomiting,
and
diarrhea
have
been
commonly
reported.
Hepatotoxicosis
and
thrombocytopenia
have
also
been
noted.53,54
Ketoconazole
is
no
longer
available
in
some
parts
of
the
world,
having
been
replaced
by
itraconazole.
There
are
no
reports
of
the
use
of
itraconazole
for
feline
HAC.

Pituitary Irradiation
For
cats
with
neurologic
signs
associated
with
a
large
pituitary
tumor,
pituitary
radiation
therapy
can
prove
beneficial.
In
one
report,
neurologic
signs
and
endocrine
signs
improved
following
radiation
therapy
in
7
cats
with
either
HAC
or
acromegaly
caused
by
large
pituitary
tumors.55
Median
survival
was
17.4
months,
but
detailed
evaluation
of
changes
in
endocrine
status
was
not
reported.
Pituitary
irradiation
has
been
associated
with
improved
diabetic
control
in
acromegalic
cats,
but
similar
improvement
in
diabetic
control
in
cats
with
HAC
has
not
been
reported.56

Prognosis
Untreated
or
unresponsive
feline
HAC
is
a
progressive
disorder
with
a
poor
prognosis.
These
cats
usually
die
from
severe
infection,
uncontrolled
DM
or
are
euthanized.
With
appropriate
therapy,
cats
with
adrenal
adenomas
or
PDH
appear
to
have
a
good
to
excellent
prognosis.
Many
of
the
diabetic
cats
with
feline
HAC
require
less
insulin
to
manage
their
diabetes.
Complete
remission
of
DM
may
occur
in
those
cats
undergoing

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