Idiopathic Hypertrophic
of the Cavernous
Lymphocytic
Cranial Pachymeningitis
Sinus Mimicking
Hypophysitis
Case Report—
—
Hiroshi
NISHIOKA, Hiroshi ITO, Jo HARAOKA, Megumi
and Fujio SHINMURA*
TAKAHASHI*,
Department of Neurosurgery, Tokyo Medical College, Tokyo; *Department of Neurosurgery,
Tokyo Metropolitan Ohtsuka Hospital, Tokyo
Abstract
A 56-year-old female presented with idiopathic hypertrophic cranial pachymeningitis
manifesting as
headache, hypopituitarism,
and diabetes insipidus, mimicking lymphocytic hypophysitis. Five months
later, she complained of double vision and unusual right facial sensation. The diagnosis was based on
magnetic resonance imaging, angiography, and meningeal biopsy via transsphenoidal
surgery, and ex
clusion of other known causes of pachymeningitis.
Despite initial response to steroid treatment, her
symptoms recurred repeatedly and she became steroid-dependent.
Repetition of short-term steroid pulse
therapy restrained the deterioration of her condition. The clinical presentation of idiopathic hyper
trophic cranial pachymeningitis
is variable, and it may develop with signs of adjacent tissue involve
ment. Resultant secondary hypophysitis must be differentiated from lymphocytic hypophysitis. Initial
steroid therapy is effective in improving symptoms, but should be carefully considered since the natur
al course of this disease seems to be self-limited.
Key words:
secondary
hypertrophic
cranial
hypophysitis,
pachymeningitis,
lymphocytic
cavernous
sinus,
Introduction
Idiopathic
hypertrophic
cranial
pituitary
gland,
hypophysitis
Case
pachymeningitis
(IHCP) is a rare chronic inflammatory
lesion of the
cranial dura mater and mainly affects the skull base
dura. Modern neuroimaging
methods are detecting
this disease with increasing
frequency.
However,
the clinical presentation
of this lesion varies, and the
natural course is still unknown.
We report a unique case of IHCP of the cavernous
sinus involving the pituitary gland and the internal
carotid arteries (ICAs), manifesting as hypopi
tuitarism, diabetes insipidus, and cavernous sinus
syndrome, which recurred repeatedly despite an ini
tial response to steroid treatment.
Report
A 56-year-old post-menopausal
female presented
with headache and central diabetes insipidus in De
cember 1995. She had had no medical problems be
fore 1995. In March
1996, she developed
hypopituitarism, and magnetic resonance (MR) im
aging demonstrated a sellar lesion, which yielded a
tentative diagnosis of lymphocytic hypophysitis. In
addition to hormone replacement with thyroid hor
mone and desmopressin
acetate (DDAVP), cor
ticosteroid therapy was initiated. This treatment
achieved transient improvement of headache and
adenohypophysial
dysfunction. Five months later,
she was referred to our department because of recur
rent hypopituitarism,
uncontrolled diabetes insipi
dus, and cavernous sinus syndrome.
On admission,
she complained
of headache,
dou
ble vision, right facial numbness,
general fatigue,
Received
1998
December
24,
1997;
Accepted
March
24,
polydipsia,
Her urine
and polyuria.
She appeared
lethargic.
volume was 5600-6300 ml/day (density
1.002-1.005 g/ml) when receiving 10,ug per day
DDAVP. Neurological examination revealed bitem
poral inferior quadrantanopia, right abducens nerve
palsy, and right trigeminal nerve dysesthesia. Rou
tine laboratory test results were normal apart from a
slight elevation of C-reactive protein level and leu
kocytosis. Titers for common viruses (Epstein-Barr,
cytomegalovirus, enteric cytopathogenic human or
phan, influenza, parainfluenza, herpes zoster, and
herpes simplex), bacteria, and toxoplasmosis were
negative. Serum tests for rheumatoid arthritis and
syphilis, and anti-human immunodeficiency virus-1
antibody were negative. In addition, test for
antipituitary
antibodies,
other
autoantibodies
(antinuclear,
anti-deoxyribonucleic
acid,
anti
ribonucleoprotein
antibodies), and lupus erythema
tosus factor were all negative. Her serum angioten
sin-converting
enzyme level was normal. Chest
radiography and abdominal and thoracic computed
tomography (CT) showed no abnormalities. Exami
nation of the cerebrospinal fluid showed normal cell
numbers and levels of proteins, and the cytological
examination and culture were negative. Endocrino
logical evaluation revealed hypopituitarism
with
slight hyperprolactinemia:
adrenocorticotropic
hor
mone (ACTH) < 5 pg/ml (normal 9-52), cortisol
< 1.0µg/dl (normal 4-18.3), luteinizing hormone (LH)
< 0.5 mIU/ml (normal 9-38), follicle-stimulating hor
mone (FSH) 0.7 mIU/ml (normal 26-113), thyroid
stimulating hormone (TSH) 0.09,uU/ml (normal
0.34-3.5), growth hormone (GH) 0.42 ng/ml (normal
0.66-3.68), and prolactin 16 ng/ml (normal 1.4-14.6).
These adenohypophysial hormones showed low or
no response to the triple stimulation (thyrotropin
releasing hormone, LH-releasing hormone, insulin)
test. The plasma
antidiuretic
<0.3 pg/ml (normal 0.3-3.5).
hormone
level
was
Skull radiography and brain CT were normal. MR
imaging disclosed a sellar and parasellar lesion in
volving the pituitary gland and the bilateral caver
nous sinuses particularly on the right side. T1-weight
ed MR imaging showed the pituitary gland and the
cavernous sinus were ill-defined (Fig. 1 left), and loss
of the hyperintense signal of the neurohypophysis
was observed (Fig. 1 right). T2-weighted MR imaging
showed the cavernous sinus lesion as hypointense.
The lesion and the stalk were well enhanced
by gadolinium-diethylenetriaminepenta-acetic
acid
(Gd-DTPA) (Fig. 1 center). These MR imaging find
ings were identical to those of the initial study. On
the other hand, cerebral angiography showed promi
nent stenosis of the bilateral extradural ICAs, in the
intracavernous (C4)portion of the left ICA and the in
trapetrosal (C5)portion of the right ICA (Fig. 2). In ad
dition, the bilateral cavernous sinuses were poorly
filled in the venous phase. Thallium-201 single pho
ton emission computed tomography showed a high
accumulation on the early scan in the lesion.
Biopsy of the lesion was performed
via trans
sphenoidal
surgery to establish the diagnosis.
After
removal of the sella floor, which appeared normal, a
firm, dull-gray dural lesion was exposed. The lesion
extended continuously
inside the sella and no pituita
ry tissue could be identified.
A small biopsy speci
men was excised but no further removal of the lesion
was performed.
Histological
examination
disclosed
fibrotic and collagenous tissue with inflammatory
in
filtrates composed
of lymphocytes
and a few neu
trophils indicating
granulomatous
pachymeningitis
of unknown etiology (Fig. 3). No caseous necrosis or
Fig. 1 Coronal T1-weighted magnetic resonance images demonstrating an isointense lesion involv
ing the cavernous sinus and the pituitary gland (left), and enhancement of the lesion and stalk
by gadolinium-diethylenetriaminepenta-acetic
acid (center). Sagittal T1-weighted image show
ing loss of the hyperintense signal of the neurohypophysis
(right).
Fig. 2 Cerebral angiograms showing prominent ste
nosis of the extradural portion of the bilater
al internal carotid arteries, in the intracaver
nous (C4) portion on the left (left) and the
intrapetrosal (C5) portion on the right (right).
Fig.
4
Follow-up
magnetic
resonance
gadolinium-diethylenetriaminepenta-acetic
acid,
taken
16 months
after
mained
the
unchanged
pituitary
except
mass
for
image
biopsy,
reduction
with
re
of
lesion.
,ug per day DDAVP.
In addition,
slight
improve
ments in the facial dysesthesia
and adenohypophy
sial dysfunction
were observed.
Fig.
3
Photomicrograph
tained
via
of the biopsy
transsphenoidal
diffuse
fibrotic
ic and
slight
stain,
x 130.
thick
specimen
surgery
tissue
neutrophilic
with
ob
showing
lymphocyt
infiltration.
HE
epitheloid
granuloma
was present.
Specific stains
were negative
for fungi and acid-fast bacilli. Im
munohistochemical
staining
for GH, prolactin,
ACTH (DAKO, Carpinteria,
Calif., U.S.A.), and cx
and 8-subunits
of LH, FSH, and TSH (supplied by
the National Institute of Diabetes and Digestive and
Kidney Diseases,
Bethesda,
Md., U.S.A.) demon
strated that no adenohypophysial
cells were present
in the specimen.
Furthermore,
immunohistochemi
cal staining for UCHL-1 (DAKO, Glostrup,
Den
mark) and L-26 (DAKO, Kyoto) showed that the in
filtrating lymphocytes
were polyclonal.
The diagno
sis was IHCP. The postoperative
course was un
eventful. Her headache and double vision improved
and diabetes insipidus became controllable
with 10
One month after biopsy, she suffered recurrence
of intense headaches,
facial paresthesia,
and distur
bance of left visual acuity. Visual field and ocular
movements
were normal. Follow-up
MR imaging
with Gd-DTPA revealed no change. Steroid therapy
was commenced
with an initial dose of 16 mg/day of
betamethasone,
which was subsequently
tapered.
This therapy achieved immediate
improvement
of
symptoms,
but she became steroid-dependent;
her
symptoms improved with steroid administration
but
reappeared
whenever treatment
was tapered or dis
continued.
In addition, aseptic epiphyseal
necrosis
of the bilateral femurs developed, probably as a com
plication
of the steroid therapy.
Therefore,
high
dose short-term
pulse steroid therapy was initiated
at a daily dose of 1000 mg of methyl predonisolone
and tapered within a week. This regimen was repeat
ed until her symptoms
gradually improved
without
any other
complication.
Sixteen
months
after
biopsy, she remained
in good condition
without
steroid treatment, but still required hormone replace
ment therapy. On the follow-up study, MR imaging
appearance
remained
unchanged
except for reduc
tion of the pituitary lesion (Fig. 4).
Discussion
Previous
features
cases
similar
of IHCP
to those
have demonstrated
clinical
in the present
case. The 47
craniopharyngioma,
Rathke's
cleft cyst, and other
patients, including ours, were aged from 19 to 75
vascular
events
in
the
pituitary.
Lymphocytic
years (mean 50.3 years) with no sex predominence
hypophysitis
lacks
specific
and
reliable
clinicopatho
(24 males and 23 females). The location of the lesion
logical
diagnostic
markers,
1,26,28,32)so various
atypi
showed three distinct patterns: the most frequent
cal
cases
reported
as
lymphocytic
hypophysitis
may
pattern mainly affected the falco-tentorial
and
be
secondary
hypophysitis.
Inflammation
of
lympho
posterior fossa dura mater (20 cases), 2,3'7,8,10,17,19-24,31,34)
cytic hypophysitis,
probably
an autoimmune
lesion,
the lesion was localized in the parasellar and caver
is essentially
limited
to the pituitary
gland, with in
nous sinus dura mater (9 cases),10-12,14,25,27,30,36)
or the
frequent
extension
to the hypothalamus,
but never to
lesion affected both regions or diffuse cranial dura
the cerebrum,
causing
encephalitis
or basal meningi
and, on occasion, the upper cervical spine (14
tis. In the present
case, lymphocytic
hypophysitis
is
cases).6,10,11,15,16,18,20,21,31,33)
Therefore, IHCP tends to
originate in the midline dura producing symmetrical
unlikely
to have preceded
and caused
secondary
lesions.31) Long histories of headaches and progres
pachymeningitis
of the cavernous
sinus.
MR imag
sive cranial nerve paresis (30 cases) were the most
ing showed
hypertrophic
pachymeningitis
of the
common clinical symptoms, and cavernous sinus
cavernous
sinus at the onset of pituitary
symptoms,
syndrome
was
also
common
(15
and this remained
unchanged
during
the course
and
cases).10'11'14-16,21'23'25'27'30'31'36)
In addition to multiple
was unrelated
to either symptoms
or treatments.
In
cranial nerve pareses caused by fibrous entrapment
addition,
angiography
showed
involvement
of the
or ischemic damage of the nerve, adjacent tissue in
bilateral
ICAs. Therefore,
the present
case indicates
volvement such as encephalitis (6 cases), 15,20,22,23,29)that IHCP can involve the pituitary
gland and cause
hydrocephalus (5 cases), 3,19,22,23'34)
sinus thrombosis (3
associated
symptomatic
secondary
hypophystis.
Fur
cases), 10,17,20)
and the pituitary lesion were reported.
thermore,
our case
is similar
to fibrosing
pseu
Pituitary
involvement
was observed
in six
dotumor
of the sella and parasellar
region,
a local
ized form of IHCP.4,9,30)
cases, 15,18'25'30'36)
but apparent hypopituitarism and dia
The diagnosis
of IHCP is based on exclusion
of
betes insipidus were only observed separately in one
many other known causes of dural thickening.
Vari
case each15,30)apart from the present case. The initial
ous bacterial and fungal infections,
some of which
presentation
of our case mimicked lymphocytic
are clinically difficult to detect even with biopsy and
hypophysitis although inflammation of the pituitary
culture
studies,
can
cause
pachymeningitis.
gland was not histologically identified. It was sug
Although MR imaging is useful in the tentative diag
gested that visual defect in our case was also caused
nosis of hypertrophic
pachymeningitis,
aggressive
by either ischemic or direct inflammatory damage of
efforts to clarify the etiology are important before in
the optic nerve. Involvement of the ICA in IHCP has
stituting steroid treatment.
Corticosteroid
therapy is
also been reported.36)
Lymphocytic
hypophysitis
is a distinct
entity
in
volving
a chronic
inflammatory
lesion mainly affect
ing the adenohypophysis.
This disease
commonly
affects
females
during
late pregnancy
or in the
postpartum
period,
and can cause
visual disorders
and hypopituitarism.
However,
the clinical
presenta
tion
of lymphocytic
hypophysitis
is also
varia
ble. 1'13,28,35)This disease
can also affect males
and
post-menopausal
females.
In addition
to neuro
hypophysial
involvement
manifesting
as diabetes
in
sipidus,
presentations
with
hyperprolactinemia,
cavernous
sinus
syndrome,
and occlusion
of the
bilateral
carotid
arteries
have been described.
A case
of recurrence
has
also
been
reported.")
Conse
quently,
although
IHCP and lymphocytic
hypophysi
tis are quite different
entities,
they may exhibit simi
lar clinical
features.
Hypophysitis
originating
from various
associated
pathological
hypophysitis,32)
nal lymphocytic
tis is associated
processes,
also
called
secondary
should
be differentiated
from origi
hypophysitis.
Secondary
hypophysi
with various
sellar lesions including
both therapeutic
and diagnostic
for IHCP.
In most
patients (35 of 37 reported cases) initial steroid ther
apy was effective in improving
the clinical symp
toms, particularly
headaches.
However,
MR imag
ing findings did not change after the therapy in 12 of
20 patients, and symptoms recurred despite steroid
treatment
in 25 of 35 patients.
Most patients with
recurrent
IHCP became steroid-dependent,
and side
effects of the steroid
therapy
were reported
in
some. 20'22,23'29)
Although surgical excision is occasional
ly necessary
to alleviate
mass effect of the le
sion, 3,5,21'29)
the effectiveness
of immunosuppressive
drugs and radiation
therapy
is uncertain.
Conse
quently, IHCP is a slowly progressive
disease and
the natural history, which seems to be self-limited,
may be little modified by these treatments.3,21,22) To
avoid the risk of steroid dependence,
as well as the
risk of worsening
occult bacterial
or fungal infec
tions, unconsidered
and unnecessary
high-dose
long-term steroid treatment
must be avoided. Short
term steroid pulse therapy, repeated with increased
dose when ineffective,
may be the best present
strategy
for patients
with an accurate
diagnosis
IHCP, based on surgical
biopsy and decompression
of mass lesions.
gery
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Address reprint requests to: H. Nishioka,
M.D., Depart
ment of Neurosurgery,
Tokyo Medical College, 6-7-1
Nishishinjuku,
Shinjuku-ku,
Tokyo 160-0023, Japan.