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Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.
[cushing syndrome]
Bilateral
macronodular
adrenal
hyperplasia
is
a
rare
cause
of
primary
adrenal
Cushing
's
syndrome
.
In
this
form
of
hyperplasia
,
hypersecretion
of
cortisol
suppresses
the
release
of
corticotropin
by
pituitary
corticotrophs
,
which
results
in
low
plasma
corticotropin
levels
.
Thus
,
the
disease
has
been
termed
corticotropin-independent
macronodular
adrenal
hyperplasia
.
We
examined
the
abnormal
production
of
corticotropin
in
these
hyperplastic
adrenal
glands
.
We
obtained
specimens
of
hyperplastic
macronodular
adrenal
tissue
from
30
patients
with
primary
adrenal
disease
.
The
corticotropin
precursor
proopiomelanocortin
and
corticotropin
expression
were
assessed
by
means
of
a
polymerase-chain-reaction
assay
and
immunohistochemical
analysis
.
The
production
of
corticotropin
and
cortisol
was
assessed
in
11
specimens
with
the
use
of
incubated
explants
and
cell
cultures
coupled
with
hormone
assays
.
Corticotropin
levels
were
measured
in
adrenal
and
peripheral
venous
blood
samples
from
2
patients
.
The
expression
of
proopiomelanocortin
messenger
RNA
(
mRNA
)
was
detected
in
all
samples
of
hyperplastic
adrenal
tissue
.
Corticotropin
was
detected
in
steroidogenic
cells
arranged
in
clusters
that
were
disseminated
throughout
the
adrenal
specimens
.
Adrenal
corticotropin
levels
were
higher
in
adrenal
venous
blood
samples
than
in
peripheral
venous
samples
,
a
finding
that
was
consistent
with
local
production
of
the
peptide
within
the
hyperplastic
adrenals
.
The
release
of
adrenal
corticotropin
was
stimulated
by
ligands
of
aberrant
membrane
receptors
but
not
by
corticotropin-releasing
hormone
or
dexamethasone
.
A
semiquantitative
score
for
corticotropin
immunostaining
in
the
samples
correlated
with
basal
plasma
cortisol
levels
.
Corticotropin-receptor
antagonists
significantly
inhibited
in
vitro
cortisol
secretion
.
Cortisol
secretion
by
the
adrenals
in
patients
with
macronodular
hyperplasia
and
Cushing
's
syndrome
appears
to
be
regulated
by
corticotropin
,
which
is
produced
by
a
subpopulation
of
steroidogenic
cells
in
the
hyperplastic
adrenals
.
Thus
,
the
hypercortisolism
associated
with
bilateral
macronodular
adrenal
hyperplasia
appears
to
be
corticotropin-dependent
.
(
Funded
by
the
Agence
Nationale
de
la
Recherche
and
others
.
)
.
Diseases
Validation
Diseases presenting
"bilateral macronodular adrenal hyperplasia"
symptom
cushing syndrome
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