Živilė Vaičekauskytė1, Ieva Monika Žiaukaitė1, Dr. Greta Pšemeneckienė1
1Lithuanian University of Health Sciences, Medical Academy, Faculty of medicine. Kaunas, Lithuania.
Abstract
Empty sella is usually an accidental finding in visual brain examinations without clinical presentation. However, some of them diagnosed with empty sella syndrome experience a variety of symptoms. One of many concerning symptoms are headaches and visual disturbance which are caused by increased intracranial pressure. In rare cases increased intracranial pressure can result in critical conditions as in liquorrhea. In empty sella syndrome neuroendocrine system can be affected due to compression on the pituitary gland. Impairment of the neuroendocrine axis results in hormonal imbalance. Diagnosing empty sella syndrome is challenging for physicians. Due to the wide range of symptoms, patients are often examined by several specialists who only focus on the clinical manifestations of their field of expertise and an accurate diagnosis is made after years. In absence of clear diagnostic and treatment algorithms, patients with empty sella syndrome face many problems related to regular disease monitoring. There are no confirmed recommendations which specialist has to manage patients with empty sella syndrome. Currently, these patients are supervised by a multidisciplinary team consisting a neurologists, ophthalmologists, and endocrinologists. In this article, we report a case of empty sella syndrome with multiple diagnostic challenges.
Keywords: empty sella syndrome, empty sella, intracranial hypertension, hypophyseal axis.
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Medical Sciences 2020 Vol. 8 (15), p. 156-163
Diagnostic pitfalls of Empty Sella Syndrome: a case report
Živilė Vaičekauskytė
1
, Ieva Monika Žiaukaitė
1
, Dr. Greta Pšemeneckienė
1
1
Lithuanian University of Health Sciences, Medical Academy, Faculty of medicine. Kaunas,
Lithuania.
Abstract
Empty sella is usually an accidental finding in visual brain examinations without clinical presentation.
However, some of them diagnosed with empty sella syndrome experience a variety of symptoms. One of
many concerning symptoms are headaches and visual disturbance which are caused by increased intracranial
pressure. In rare cases increased intracranial pressure can result in critical conditions as in liquorrhea. In
empty sella syndrome neuroendocrine system can be affected due to compression on the pituitary gland.
Impairment of the neuroendocrine axis results in hormonal imbalance. Diagnosing empty sella syndrome is
challenging for physicians. Due to the wide range of symptoms, patients are often examined by several
specialists who only focus on the clinical manifestations of their field of expertise and an accurate diagnosis is
made after years. In absence of clear diagnostic and treatment algorithms, patients with empty sella syndrome
face many problems related to regular disease monitoring. There are no confirmed recommendations which
specialist has to manage patients with empty sella syndrome. Currently, these patients are supervised by a
multidisciplinary team consisting a neurologists, ophthalmologists, and endocrinologists. In this article, we
report a case of empty sella syndrome with multiple diagnostic challenges.
Keywords: empty sella syndrome, empty sella, intracranial hypertension, hypophyseal axis.
Journal of Medical Sciences. April 30, 2020 - Volume 8 | Issue 15. Electronic-ISSN: 2345-0592
157
Introduction
Empty sella (ES) most often is an incidental finding
in brain imaging. Commonly it is asymptomatic, but
in rare cases ES appears with serious endocrine,
nervous system and visual symptoms and therefore is
termed as empty sella syndrome (ESS). We report a
case of ESS in a young woman with enigmatic
medical history including multiple co-exiting
diseases.
Case report
In 2011, 21-year-old patient presented with sudden
onset anisocoria without any visual impairment or
other leading symptoms. On fundoscopic
examination bilateral edema of the optical nerve disc
(OND) was observed. Two years later, patient
complained about recurring frontal one-sided
headaches. These symptoms were considered as
migraine without aura. Magnetic resonance
tomography (MRT) revealed haimoiritis and
ethmoiditis, suprasellar cistern prolapse into sella
turcica and normal sized hypophysis. In order to
exclude sinusitis computerized tomography (CT)
was performed. It showed a sphenoidal sinus cyst
which could been the reason for frontal one-sided
headaches. Therefore, transsphenoidal cystectomy
was performed and headaches relieved until further
notice. Around the same time patient developed
endocrine symptoms. The patient noted rapid weight
gain (about 14 – 15 kilograms per year) even though
eating habits and physical activity have not changed.
Thyroid gland dysfunction was suspected but only
euthyroid diffuse goiter was revealed. In addition,
laboratory tests detected slight elevated hormone
levels of prolactin (102 mIU/l) and cortisol (morning
1136 nmol/l, evening 1118 nmol/l) while
adrenocorticotropic hormone (ACTH) was normal
(morning 5,8 µmol/l). Patient was hospitalized for
further examination with suspicion of Cushing‘s
syndrome. Due to nearly normal cortisol levels
(morning 762,51 nmol/l, evening 240,27 nmol/l),
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normal ACTH (6,4 µmol/l) and only slight
pathological Dexamethasone suppression test (54,8
nmol/l), diagnosis has not been confirmed. The
patient was advised to discontinue oral
contraceptives and repeat blood analysis. Slightly
elevated cortisol (cortisol morning 1007 nmol/l and
evening 642 nmol/l) and normal ACTH (8,8 µmol/l)
were received.
In 2017 repetitive transient vision dysfunction
occurred and headache returned. The patient was
hospitalized for detailed examination. MRI revealed
enlargement of sella turica partially filled with
cerebrospinal fluid (CSF) and compressing
hypophysis the fundus of sella turcica. During the
year, complains of visual dysfunction became worse
accompanied by impediment of vision field, blurred
vision and amaurosis fugax alternately of both eyes
at night time. Neuroophthalmological examination
revealed bilateral edema of OND. Based on
complains of headaches, visual impairment, both
sided papilledema and MRI findings lumbar
puncture was considered. Elevated intracranial
pressure (40 mmH
2
0) was measured. In absence of
inflammatory or other pathological signs in CSF and
due to triad of ophthalmological, neurological and
endocrinological symptoms, in MRI detected ES,
condition assessed as ESS. Therefore, benign
intracranial hypertension was treated with
acetazolamide 500 mg per day, unfortunately
treatment was not effective. Patient repeatedly
presented with progressive vision dysfunction.
Treatment with intravenous mannitol was induced.
Patient refused further examination and was released
with recommended outpatient treatment including
acetazolamide which later was discontinued in
consequence of renal insufficiency.
Endocrinological symptoms progressed further by
the time. In 2018, patient complained of irresistible
weight gaining, dry skin, dandruff and falling hair,
irregular menstrual cycle and constantly elevated
blood pressure. The patient was examined for
imbalance of hypophyseal axis hormones.
Laboratory tests detected reduced levels of
somatotropin (0,18 mU/l) and insulin-like growth
factor (10,9 nmol/l) and use of growth hormone
analogues was recommended. Although cortisol
levels were normal (morning 409 nmol/l, cortisol in
24h urine 336,3 nmol/l), clinical appearance of
Cushing syndrome remains. Based on elevated
aldosterone-to-renin ratio (ARR: 159) aldosterone
suppression test was considered and ARR of 61 was
evaluated as marginal. Since partial adrenal gland
failure cannot be ruled out, in purpose to avoid
severe hypercortisolism, hydrocortisone was
prescribed to use before stressful situations. In
addition, because of ovarian cyst and persisting
anovulation in medical history, polycystic ovarian
syndrome was diagnosed.
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According to anamnesis, in 2006, patient was
involved in a car accident, after which she suffered
from bone fractures and contusions including head.
At this time Neurosurgical pathology was excluded.
After trauma patient had no complains until 2013.
Further, in 2011, patient suffered from acute kidney
failure due to chronic pyelonephritis and interstitial
nephritis. Besides that, partial adrenal failure without
known cause was diagnosed.
To sum up, over a few years gradually progressing
triad of neurological, ophthalmological and
endocrinological clinical symptoms and MRI finding
of ES were considered to be ESS. The cause for this
remains unclear. It is to be questioned whether
endocrinological symptoms emerged due to elevated
intracranial pressure or vice versa – endocrinological
or other conditions, in this case related to head
trauma or sinus operation, could have caused
intracranial hypertension. Congenital disorders were
not suspected.
Literature review
Empty sella syndrome (ESS) defines with an unclear
pathogenesis until nowadays. It is known that
incomplete formation of the sellar diaphragm, upper-
sella and pituitary factors could be determining
formation of empty sella (ES) and an ESS in a
following. Upper sella factors are persistent or
intermittent intracranial hypertension, CSF
pulsatility, obesity and systematic arterial
hyperstension, and pituitary factors are
compensatory pituitary hypertrophy to primary
hormonal deficit, pregnancy, lactation, menopause,
hypophysitis [1]. According to pathogenesis ES is
classified into primary (PES) and secondary empty
sella (SES).
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Etiopathogenesis
About 22 – 77% of PES cases present with
insufficient sellar diaphragm [1]. The main cause is
an anatomic defect of the diaphragma sellae that
might be congenital. However, no clear genetic
association is known [2]. PES occurs when increased
intracranial pressure causes herniation of
subarachnoid space which leads to compression of
the normal pituitary gland. As a consequence,
cerebrospinal fluid (CSF) accumulates in the sella
turcica [3] resulting in enlargement of the sella
turcica and pituitary gland flattening [4]. SES
appears as a consequence of pituitary gland damage
or injury [5]. Most commonly SES is the result of the
pituitary gland atrophy previously due to pituitary
adenoma, Sheehan’s syndrome, craniocerebral
trauma, after radiotherapy or diseases resulting in
glandular infection or infarction. Further, this leads
to CSF accumulation in the sella turcica [3].
Pulsation of CSF to the pituitary gland or pituitary
stalk provoke glandular dysfunctions [2, 6].
Clinical features
ESS can lead to endocrinological and neuro-
ophthalmological symptoms. 40% of patients may
experience headaches and occasionally neurological
dysfunction such as visual field disturbance, mostly
bitemporal hemianopsia or hemifield slide
phenomena, as a consequence of elevated
intracranial pressure [2, 7, 8, 9]. In our presented
case visual impairment occurred primarily and
progressed constantly. Headache as well presented in
a very beginning but its differential diagnosis was
more complicated due to other conditions. Present
intracranial hypertension helped to confirm ESS
diagnosis. According to literature, liquorrhea can
occur due to pulsative movements of CSF that may
erode into sphenoid sinus [1, 10]. All
endocrinological symptoms are associated with
hypothalamic–pituitary–endocrine axis suppression
on level of the pituitary gland. Therefore, in ESS
pituitary gland secretion can be insufficient. About
20% of patients present with hormone disorders
which can be the first and only sign of ESS. They are
mostly revealed by menstrual irregularities,
galactorrhea, hirsutism and sterility [11]. Ghatnatti et
al, 2012, identified hyperprolactinemia as most
common endocrine abnormality [12]. There is no
exception in this case. Endocrinological
abnormalities were noticed through infertility and
symptoms of partial adrenal gland failure.
Laboratory test could not confirm the diagnosis.
Furthermore, PES is often associated with obesity
and high blood pressure. Even 50% of females are
overweight or obese [6, 13]. These clinical features
have great importance in the presented case. Some
rare cases present psychiatric manifestations in ESS
but relation between ESS and psychiatric symptoms
is not determined yet and ES is usually only
incidental finding [14, 15].
All this considered, ESS diagnosis is made based
upon identification of characteristic symptoms, a
detailed patient history, a thorough clinical
evaluation and specialized imaging techniques. If ES
is diagnosed even though there are no symptoms, it
is usually a coincidental finding [16]. ES is
confirmed through magnetic resonance (MR) or
computerized tomography (CT) in patients with
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161
contraindications to MR [1]. Radiological findings
are distinct between partial ES (sella turcica is filled
with CSF up to 50 %) and complete ES (filled with
CSF more than 50 %) [3, 17]. Pituitary function
should be checked as well in asymptomatic patients
because in 52% incidental cases hypopituitarism
associated with ESS is revealed by measuring
hormone levels [2, 10, 18].
Treatment
Treatment should be arranged according to specific
symptoms and their severity. Patients are usually
treated multidisciplinary by a team including a
neurologist, endocrinologist and ophthalmologist [1].
Intracranial hypertension and therefore following
symptoms should be corrected in first stage of
treatment. If overweight or obesity is considered as
main cause of intracranial hypertension, weight loss
is actively suggested for the patients as the most
important part of treatment [19]. First choice of
medication to reduce intracranial pressure are
osmotic diuretics, such as acetozolamide or escin [1].
Invasive procedures such as placing a
lumboperitoneal shunt can be effective if visual
impairment is progressive and very severe as well
when non-invasive treatment is not effective [16,
20].
Hormonal imbalance is commonly treated by
endocrinologists adjusting precisely combined
hormonal therapy. Any hormone deficiency should
be replaced in a slow progression. Treatment begins
with hydrocortisone, followed by levothyroxine.
After successful substitution sexual hormones can be
added. If hyperprolactinemia occurs, dopamine
agonist drugs can improve symptoms [1, 21].
ESS is usually a benign condition and does not
determine life expectancy. But prognosis and quality
of life depends on hormone deficiency and hormonal
treatment [4]. Patients with absent symptoms and
incidental diagnosed ES, should be monitored for
hormonal imbalance or visual impairment [21].
Although, sometimes patients can not specify their
well-being and abnormal conditions seem to be fine
as long as specialists ask particular questions and
make detailed examination. While ESS occurs with
many symptoms, it remains unclear which specialist
should fully take care of these patients.
Conclusion
Empty sella is usually an incidental finding in brain
visual examinations. Although, empty sella can
occasionally present with clinical triad of
neurological, ophthalmological and endocrinological
symptoms that are considered as empty sella
syndrome. Variety of symptoms make diagnosis
confirmation challenging. The treatment as well
require a multidisciplinary team. Unfortunately,
diagnostic and treatment algorithms remain unclear.
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