Empty sella syndrome (ESS), also known as arachnoidocele, is a disorder in

which the subarachnoid space herniates into the sella turcica causing compression
and flattening of the pituitary gland and stretching of the pituitary stalk. Over the
years, the term empty sell was adapted further by radiologists observing a similar
phenomenon in CTs and MRIs of the brain. This activity articulates how to
properly evaluate for this condition, and highlights the role of the interprofessional
team in caring for patients with this condition.

Objectives:

 Review the causes of empty sella syndrome.

 Describe the history and physical exam of a patient with empty sella syndrome.
 Summarize the treatment of empty sella syndrome.
 Outline the importance of enhancing care coordination among the
interprofessional team to ensure proper evaluation and management of empty sella
syndrome.

Introduction
Empty sella syndrome (ESS), also known as arachnoidocele, is a disorder in
which the subarachnoid space herniates into the sella turcica causing compression
and flattening of the pituitary gland and stretching of the pituitary stalk.  There is
still some debate as to who first coined the term “empty sella”; W. Bush vs.
Sheehan and Summer. Both used this term around the 1950s to describe a
phenomenon recognized in cadavers in which there was an empty appearance of
the sella turcica and flattened pituitary gland. Over the following years, the term
was adapted further by radiologists observing a similar phenomenon in computed
tomograms (CTs) and magnetic resonance imaging scans (MRIs) of the brain.

Etiology
Regarding pathophysiology and etiology, empty sella syndrome (ESS) subdivides
into two categories: primary empty sella syndrome (PES) and secondary empty
sella syndrome (SES). Although this will use this distinction, it is worth noting
that both primary and secondary empty sella can be thought of and treated as one
entity: ESS. 

PES is a disorder caused by the incompetence of the diaphragma sellae and
resultant herniation of CSF into the sella turcica. There is no clear genetic
association known to predispose someone to develop PES, but the incompetent
diaphragma sellae is likely to present at birth. SES results from surgery, radiation,
hemorrhage, or infarction of the pituitary gland and it can happen at any time in a
person's life.

Epidemiology
Empty sella syndrome is considered to be a rare entity, but research reports its
incidence as present in 5.5 to 12% of autopsy cases, and it is also estimated to be
present in around 12% of patients undergoing neuroimaging.[1] Some reports
note an even higher incidence in clinical practice with estimates of up to 35%.
[1] It demonstrates a female predilection with a ratio of 4 or 5 to 1 over males, and
it is more common in obese patients. The incidence of ESS peaks in the fourth to
the sixth decade.[1][2] Although more common in women, the pituitary
hormonal dysfunction appears to occur at higher rates in men with empty sella.

Pathophysiology
As stated above, empty sella syndrome falls into two categories: primary empty
sella syndrome and secondary empty sella syndrome.

PES is the less common of the two entities. Currently, its cause is not entirely
understood, but researchers have proposed several mechanisms including
incompetence or complete absence of the diaphragma sellae, chronic intracranial
hypertension, and temporary expansion followed by regression of the pituitary
gland.
Incompetent diaphragma sellae has been the finding in the vast majority of PES at
autopsy reports. The anomalous diaphragma sellae allows the accumulation of
cerebrospinal fluid (CSF) into the sella turcica causing remodeling and
enlargement of the sella turcica as well as flattening of the pituitary gland.

Intracranial hypertension is also thought to increase the likelihood of herniation of

CSF into the sella turcica especially if the diaphragma sellae is already
compromised. The most common neuroimaging finding in patients with
idiopathic intracranial hypertension (also known as pseudotumor cerebri) is empty
sella.[3]  Many different pathologies causing increased CSF pressures have
correlations with PES including brain tumors, idiopathic intracranial hypertension
(pseudotumor cerebri), intracranial thrombosis, and hydrocephalus. The resolution
of empty sella on imaging after treatment of intracranial hypertension illustrated
further evidence that intracranial hypertension can cause empty sella.[4]

The last proposed mechanism causing empty sella involves an initial enlargement

of the pituitary gland followed by a later decrease in gland size which creates an
empty space in which CSF can accumulate. Examples of this include a normal
increase in pituitary volume during pregnancy and lactation and then spontaneous
regression in pituitary volume during menopause in women.

SES, on the other hand, is much more common than PES. It could be the result of
the treatment of a pituitary adenoma (by either drugs, surgery, or radiotherapy),
spontaneous regression of the pituitary gland under different circumstances,
postpartum pituitary necrosis (also known as Sheehan syndrome) or lymphocytic
hypophysitis.[2]

History and Physical

History and physical exam are typically normal in patients with empty sella
syndrome because the endocrine function is usually intact. The most common
symptom associated with ESS is a headache. There is lack of evidence to support
ESS as the cause of the headache and many experts believe that the association
exists because the headache of any unrelated cause prompted imaging of the head
to be done leading to the incidental discovery of the empty sella. Other authors
consider the possibility that increased intracranial pressure and possible herniation
is the cause of the headaches; however, no confirmation of this theory exists
either.

Spontaneous cerebrospinal fluid rhinorrhea is possible as is visual field

impairment; however, both of these presentations are rare.[5]

Endocrine abnormalities are present in less than 20% of cases of the empty sella.
If the pituitary function is compromised, history and physical exam can be
consistent with any, or all, of the pituitary hormone deficiencies.

Evaluation
Testing of the entire pituitary axis is appropriate and highly recommended in
patients with empty sella syndrome after diagnosis; however, there is currently a
lack of society based guidelines.[6][7][8] In most cases, the pituitary function is
normal (despite the abnormal appearance of the pituitary gland), but in some cases
(around 20%) any, or all, of the pituitary hormone levels can be affected.
Hyperprolactinemia and growth hormone deficiency appear to be the two most
common findings in empty sella.[2][9] Hyperprolactinemia is present in 10 to
17% of cases and may result from a microprolactinoma or functional
hyperprolactinemia.[1][9] Growth hormone deficiency presents in 4 to 60% of
cases, but its clinical significance in adults is unclear.[1][6] Gonadotropin
deficiency is seen in 2 to 32% of cases while adrenocorticotropin, thyroid-
stimulating hormone, and antidiuretic hormone deficiencies are seen less
frequently, around 1% each.[6]

The following labs are necessary for the evaluation of pituitary function in any
patient found to have empty sella:
 Adrenal axis: An early morning, fasting cortisol levels are a screening
option for adrenocorticotropin (ACTH) deficiency and overtly low levels of
cortisol less than 3.0 mcg/dL are consistent with adrenal insufficiency.
Morning cortisol levels greater than 11.0 (some authors suggest 14.0)
mcg/dL make adrenal insufficiency very unlikely, while morning cortisol
levels of 3.1 to 11.0 (14.0) mcg/dL are indeterminant and can warrant further
testing such as cosyntropin (ACTH) stimulation testing. If morning cortisol
level is low, an ACTH level should be obtained and correlated to the low am
cortisol level to help differentiate primary from secondary/central adrenal
insufficiency. Metyrapone testing can also assist in this diagnosis. If
corticosteroid excess is suspected, an ACTH level again needs to be
correlated with cortisol level, and a workup for Cushing disease should be the
next step.

 Thyroid axis: thyroid-stimulating hormone (TSH) level with free thyroxine

(T4) level at the same time should be checked.

 Reproductive axis: In premenopausal women with regular menses,

gonadotropin, and estradiol levels are not necessary. If menses are irregular
or absent, then follicle-stimulating hormone (FSH) and luteinizing hormone
(LH) with estradiol levels should be checked. Postmenopausal women most
likely do not need FSH, LH, or estradiol levels checked. In men, a
testosterone level with simultaneous LH and FSH levels should be obtained. 

 Prolactin (PRL): PRL levels should be obtained. Hyperprolactinemia is

much more common than PRL deficiency. PRL elevations can be seen in
many conditions not related to ESS (ex. drugs, pregnancy, etc.) and thus
abnormalities must be correlated with the clinical presentation.

 Growth Hormone (GH), excess or deficiency: GH has a short half-life and

is pulsatile throughout the day, so measuring serum levels is not a common
practice. Insulin-like growth factor 1 (IGF-1) can be used instead as a
screening measure. However, normal levels of IGF-1 do not rule out GH
deficiency. Stimulation testing is recommended by some experts to rule out
 the possibility of GH deficiency.[6] The gold standard testing for GH
deficiency is the insulin tolerance test. Other options are GHRH plus arginine
test, glucagon stimulation, or macimorelin test.

 Antidiuretic hormone (ADH): ADH levels are not typically measured, but

the clinicians should inquire about the frequency of urination, including
nocturia, to rule out the possibility of diabetes insipidus. If suspicious of
diabetes insipidus, serum sodium, serum osmolality, and urine osmolality
should be obtained.

 Oxytocin levels are not a routine lab for screening in ESS.

Treatment / Management
In most instances, no treatment is necessary for empty sella syndrome. If there is
hormone deficiency or excess, treatment is individualized towards the hormone
derangements present.

Differential Diagnosis
Empty sella is a radiologic finding and diagnosis. Differentials relating to
this entity stem from each specific cause (ex. intracranial hypertension would have
many differentials). Please see the pathophysiology section for further details.

Prognosis
The presence of empty sella syndrome does not change life expectancy, and it is
usually a benign condition. In cases where a specific hormone deficiency or
excess is present, that specific hormone abnormality and its treatment determine
the prognosis.
Complications
Possible complications of empty sella include the development of partial, or
complete, hypopituitarism, or hormone hyperfunctioning as noted above.
Additionally, there is an association of worse outcomes for patients undergoing
pituitary surgery with known primary empty sella (ex. Cushing's disease).[10]

Deterrence and Patient Education

There is nothing in particular that patients can do to avoid this phenomenon, but
they should be aware of the need for evaluation of hormone levels at diagnosis. If
initial hormone levels are all within normal limits, no additional testing is required.

Enhancing Healthcare Team

Outcomes
Empty sella syndrome is a rare entity that is usually found incidentally during
evaluation of headache or other complaints leading to imaging of the brain/head.
Although only a small fraction of these patients have associated hormone
deficiencies, a full pituitary hormone workup is the indicated screening approach
at diagnosis, and the patients should receive an endocrinologist referral. The
optimal management approach an interprofessional team of specialty-
trained nurses and clinicians providing regular follow up, education of the patient
and family, coordination of care, and laboratory evaluation. [Level 5]

(Click Image to Enlarge)

Empty sella MRI
Image courtesy S Bhimji MD

Article Details

Article Author

Peter Ucciferro
Article Editor:

Catherine Anastasopoulou
Updated:

7/21/2021 6:56:18 AM
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Empty Sella

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References
[1]

Chiloiro S,Giampietro A,Bianchi A,Tartaglione T,Capobianco A,Anile C,De

Marinis L, DIAGNOSIS OF ENDOCRINE DISEASE: Primary empty sella: a
comprehensive review. European journal of endocrinology. 2017 Dec;  
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[2]

Guitelman M,Garcia Basavilbaso N,Vitale M,Chervin A,Katz D,Miragaya

K,Herrera J,Cornalo D,Servidio M,Boero L,Manavela M,Danilowicz K,Alfieri
A,Stalldecker G,Glerean M,Fainstein Day P,Ballarino C,Mallea Gil
MS,Rogozinski A, Primary empty sella (PES): a review of 175 cases. Pituitary.
2013 Jun;     [PubMed PMID: 22875743]
[3]

Saindane AM,Lim PP,Aiken A,Chen Z,Hudgins PA, Factors determining the

clinical significance of an     [PubMed PMID: 23617499]
[4]

Zagardo MT,Cail WS,Kelman SE,Rothman MI, Reversible empty sella in

idiopathic intracranial hypertension: an indicator of successful therapy? AJNR.
American journal of neuroradiology. 1996 Nov-Dec;     [PubMed PMID:
8933886]
[5]

Schlosser RJ,Bolger WE, Spontaneous nasal cerebrospinal fluid leaks and empty
sella syndrome: a clinical association. American journal of rhinology. 2003 Mar-
Apr;     [PubMed PMID: 12751703]
[6]

Giustina A,Aimaretti G,Bondanelli M,Buzi F,Cannavò S,Cirillo S,Colao A,De

Marinis L,Ferone D,Gasperi M,Grottoli S,Porcelli T,Ghigo E,degli Uberti E,
Primary empty sella: Why and when to investigate hypothalamic-pituitary
function. Journal of endocrinological investigation. 2010 May;     [PubMed
PMID: 20208457]
[7]

Auer MK,Stieg MR,Crispin A,Sievers C,Stalla GK,Kopczak A, Primary Empty

Sella Syndrome and the Prevalence of Hormonal Dysregulation. Deutsches
Arzteblatt international. 2018 Feb 16;     [PubMed PMID: 29510819]
[8]

Zuhur SS,Kuzu I,Ozturk FY,Uysal E,Altuntas Y, Anterior pituitary hormone

deficiency in subjects with total and partial primary empty sella: do all cases need
endocrinological evaluation? Turkish neurosurgery. 2014;     [PubMed PMID:
24848177]
[9]

De Marinis L,Bonadonna S,Bianchi A,Maira G,Giustina A, Primary empty sella.

The Journal of clinical endocrinology and metabolism. 2005 Sep;     [PubMed
PMID: 15972577]
[10]

Mehta GU,Bakhtian KD,Oldfield EH, Effect of primary empty sella syndrome on

pituitary surgery for Cushing's disease. Journal of neurosurgery. 2014 Sep;  
  [PubMed PMID: 24857241]
‫مقال‬

Empty Sella
Dragana Miljic, MD, Sandra Pekic, MD, and Vera Popovic, MD.

Author Information

Last Update: August 1, 2021.

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ABSTRACT
Empty sella is a radiological finding of a flattened pituitary in a sellar space filled
with cerebrospinal fluid. It may be primary or secondary consequent to various
processes causing injury and shrinkage of the pituitary gland (postpartum
hemorrhage, pituitary surgery, irradiation, apoplexy, infection, head trauma,
hypophysitis, etc.). The mechanisms involved in the pathogenesis of the so called
“primary empty sella” may range from continuously or intermittently increased
intracranial pressure due to idiopathic benign intracranial hypertension, obesity,
arterial hypertension, or multiple pregnancies in female patients with accompanying
insufficiency of the sellar diaphragm and changes in pituitary gland volume
(hyperplasia during pregnancy, lactation, menopause etc.). Primary empty sella can be
an incidental radiological finding in an asymptomatic patient with preserved pituitary
function. In symptomatic patients with the so called “empty sella syndrome”
(headache, visual disturbances and hormonal dysfunction), the radiological finding of
an empty sella is important in the differential diagnosis of other sellar lesions.
Hypopituitarism, partial or complete, and hyperprolactinemia are not uncommon in
these patients. The treatment of hypopituitarism and hyperprolactinemia is advocated
in all patients with confirmatory results. In patients with the secondary empty sella,
hypopituitarism is more common and more readily recognized due to damage caused
by surgery, radiation therapy, or various pathological causes. Rarely, empty sella can
be associated with hormonal hypersecretion from an “invisible” micro adenoma
producing prolactin, growth hormone (acromegaly) or ACTH (Cushing’s disease). A
wide range of radiological findings in patients with secondary and primary empty
sella coupled with clinical data (important hints from the history and data on
endocrine function) are presented for further illustration of this topic. For complete
coverage of all related areas of Endocrinology, please visit our on-line FREE web-
text, WWW.ENDOTEXT.ORG.
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HISTORY
The term ‘empty sella’ was first used by Bush in 1951 (1) to describe a peculiar
anatomical condition, observed in 40 of 788 human cadavers, particularly females,
characterized by a sella turcica with an incomplete diaphragm sellae that forms only a
small peripheral rim, with a pituitary gland not absent, but flattened in such a manner
as to form a thin layer of tissue at the bottom of the sella turcica. Kaufman (2), in
1968, speculated that ‘…empty sella is a distinct anatomical and radiographic entity,
function of an incompleteness of the diaphragma sellae and of the cerebrospinal fluid
(CSF) pressure, normal or elevated’. The role of the normal fluctuations of CSF
pressures and the effect of a superimposed prolonged increase in CSF pressure were
related to the anatomic changes involving the bony wall of the empty sella.
Go to:

DEFINITION, ETIOLOGY, AND PREVALENCE OF EMPTY SELLA

Empty sella is defined as herniation of subarachnoid space into the sella turcica
(arachnoidocele). It is a term for the radiological finding of “empty sellar space” on
magnetic resonance imaging (MRI) and computerized tomography (CT) with a
flattened pituitary and elongated stalk. It can be partial if less than 50% of sellar space
is filled with cerebro-spinal fluid (CSF), or complete if CSF fills more than 50% of
space in the sella and gland thickness is less than 2mm (3,4).
Regarding its etiology, it can be primary if there is no pathological process in the
sellar region preceding the pituitary damage or secondary if it is consequent to a
specific pathological process. Primary empty sella (PES) can be an incidental finding
or may arise during imaging for headache, endocrine disorders, neurological
symptoms, visual disturbances, abnormal sella turcica radiograph, and other reasons.
Primary empty sella (PES) can be caused by intracranial hypertension and/or
insufficiency of the sellar diaphragm in subjects with no previous history of pituitary
disease. Insufficiency of the sellar diaphragm, a deflection of dura matter separating
the suprasellar cistern from the pituitary fossa, allows unobstructed pulsatile
movements of CSF from chiasmatic cistern causing flattening of the pituitary to the
sellar floor. In extreme cases bone erosion of the sellar floor and CSF leak
(rhinorrhea) may occur, increasing the risk of meningitis. Partial or complete absence
of the sellar diaphragm has been demonstrated in patients with PES.
Intracranial pressure can be intermittently increased due to obesity, sleep apnea,
arterial hypertension, pregnancy, and labor. Intracranial hypertension may be
idiopathic or associated with other intracranial processes such as tumors, venous
thrombosis, infections, or malformations. Idiopathic intracranial hypertension (IIH) or
“pseudo-tumor cerebri” is a rare condition affecting 1 in 100,000 persons. It can be
due to impaired CSF absorption, increased CSF secretion and/or increased capillary
permeability (5). Impaired CSF dynamics and absorption have been found in up to
77% and 84% of patients with PES, respectively (6), The prevalence of PES is very
high in patients with IIH ranging from 70-94% (4).
Changes in the pituitary gland volume may also be involved in the pathogenesis of
empty sella syndrome including hyperplasia during pregnancy and lactation and
pituitary involution after menopause accounting for the significantly higher
prevalence of this condition in female patients (female to male ratio 5:1).
Factors involved in the pathogenesis of primary empty sella are shown in Figure 1.
Secondary empty sella is more common and is related to various pathological
processes of the sellar region. Among many causes of pituitary tumor shrinkage
occurring after medical treatment, surgery, radiotherapy, and apoplexy of a pituitary
adenoma are frequent causes of secondary empty sella. Likewise, postpartum pituitary
necrosis, pituitary infection, hypophysitis, and traumatic brain injury may lead to
pituitary atrophy. The diagnosis of secondary empty sella is more difficult if there is
no known underlying pathology involving the pituitary gland. In these cases, the sella
is normal in size, and the function of the flattened pituitary gland may or may not be
compromised. Such is the case in congenital causes of hypopituitarism both acquired
and genetic, presenting with a hypoplastic pituitary gland and ectopic posterior lobe.
Large intracranial tumors such as slow-growing meningiomas can also cause
increased intracranial pressure and secondary empty sella in a significant number of
patients. Pituitary MRI images of patients with secondary and primary empty sella are
presented in the section dedicated to radiological appearance of an empty sella (Fig.
2-6). Associated risk factors for primary and secondary empty sella are shown
in Table 1.
The reported prevalence of empty sella depends on techniques used for detection. In
autopsy studies empty sella has been found in up to 5.5-12% cases (1,2), On imaging
the overall incidence has been estimated at 12% (4). The prevalence of PES is very
high in patients with IIH.

Table 1.
Associated Risk Factors for Primary and Secondary Empty Sella

Primary Empty Sella (PES) Secondary Empty Sella (SES)

Female sex Medical therapy

Multiple pregnancies
Obesity and sleep apnea
Arterial hypertension
Benign intracranial
hypertension
Pituitary surgery
Irradiation
Pituitary apoplexy
Sheehan’s syndrome
Traumatic brain injury
Congenital hypopituitarism
Figure 1.
Factors involved in pathogenesis of primary empty sella including the upper-sellar
factors, incompetence or incomplete formation of the sellar diaphragm, and pituitary
factors associated with the variation in the pituitary volume. Modified from
Bioscientifica Ltd., Chiloiro S et al, European Journal of Endocrinology (2017) 177,
R275–R285
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RADIOLOGICAL APPEARANCE OF EMPTY SELLA

Most commonly an empty sella is incidentally discovered during MRI or CT imaging
or during evaluation for headache, endocrine, neurological or visual disturbances.
Less commonly it is observed after additional imaging for abnormal sella turcica
radiographs. Chronic intracranial hypertension can lead to sellar remodeling and
enlargement with thinning of the sellar floor and rarely rhinorrhea.
On typical presentation CSF filling is in continuity with overlying subarachnoid
spaces and the residual pituitary gland is flattened against the sellar floor of enlarged
bony sella with pituitary volume usually less than 611.21 mm3 (7). The differential
diagnosis with cystic lesions and congenital pituitary abnormalities may pose a
challenge. The stalk is usually thinned and located in the midline. Asymmetry is a
frequent sign of the secondary empty sella. In rare cases the chiasm can herniate into
the sella in cases of both primary and secondary etiology. Indirect signs of intracranial
hypertension may also be present such as flattening of the posterior sclera, prominent
subarachnoid spaces along the optic nerves, vertical tortuosity of the optic nerve
sheath complex, and increased width of the optic nerve sheaths (8).
Sagittal and coronal T1-weighted (T1W) contrast enhanced images and coronal T2-
weighted (T2W) images are strongly indicated for MR studies because they show
CSF within the sella. On FLAIR sequences the intrasellar fluid completely suppresses
and it presents without restriction in DWI sequences. After contrast T1W images
show normal enhancement of residual pituitary gland and the stalk in PES in contrast
to scaring and distortion in SES.
In patients with congenital hypopituitarism an ectopic posterior pituitary, stalk
duplication or absence may be present in combination with other midline defect
(agenesis of corpus callosum, supraoptic dysplasia, etc.).
Figures 2, 3, 4, 5 represent various MRI findings of patients with secondary empty
sella due to postpartum hemorrhage (Sheehan’s syndrome Fig. 2), lymphocytic
hypophysitis (Fig. 3), shrinkage of a macroprolactinoma after successful treatment
with cabergoline (Fig.4), and congenital hypopituitarism with empty sella (Fig.5)
Figure 2.
Sagittal T1W images of two patients with empty sella and Sheehan’s syndrome
Left Panel (sagittal T1W image without contrast) and Right (sagittal T1W image after
contrast enhancement) represent the MRI appearance of empty sella in two patients
with Sheehan’s syndrome. Both patients presented with hyponatremic coma due to
unrecognized panhypopituitarism and infection 3 and 20 years after delivery
complicated by postpartum hemorrhage.

Figure 3.
Contrast enhanced coronal and sagittal T1W images of lymphocytic hypophysitis
spontaneous evolution from the presentation (panel A, B), after 4 (panel C) and 10
years (panel D) of follow-up resulting in secondary empty sella.
Figure 4.
Coronal T1W images demonstrating a pituitary tumor (macroprolactinoma) shrinkage
in a patient treated with the dopamine agonist cabergoline for 10 years. The patient
presented with hyperprolactinemia causing galactorrhea-amenorrhea, secondary
adrenal insufficiency and central hypothyroidism. Hyperprolactinemia and adrenal
insufficiency completely recovered during follow up.

Figure 5.
Sagittal T1W showing small pituitary gland found at the bottom of sella, thin stalk
and ectopic posterior lobe in a young adult with isolated childhood-onset growth
hormone deficiency (congenital).
Figure 6.
Sagittal T1W images of pituitary stalk pressed against the dorsum sellae causing mild
hyperprolactinemia in a patient with primary empty sella.
Go to:

PRIMARY EMPTY SELLA (PES) AND EMPTY SELLA SYNDROME

Epidemiologically, this is associated with female sex (female to male ratio 5:1),
multiple pregnancies, obesity, arterial hypertension and middle age. It may present
with headaches, endocrine dysfunction, and visual disturbances due to pressure on the
neighboring structures.
A typical clinical picture consists of headache and obesity. Women in the
reproductive age may be affected by menstrual irregularities, galactorrhea and
sterility. Man can develop gynecomastia and sexual disturbances. Primary empty sella
due to the syndrome of increased intracranial pressure can also be associated with
symptoms of intracranial hypertension.

Pathogenesis of Primary Empty Sella (PES)

Pregnancy may trigger the onset of PES. It is associated with pituitary hyperplasia and
CSF hypertension especially in multiple pregnancies. PES has also been associated
with CSF hypertension related to obesity and arterial hypertension. In the largest
study with 175 patients, multiple pregnancies were reported in 58.3% women with
PES, while obesity and arterial hypertension were recorded in 49.5% and 27.3% of
patients (8). In patients with benign intracranial hypertension, empty sella is a
common finding.

Endocrine Dysfunction in PES

Hyperprolactinemia, usually mild (less than 50 ng/ml), is present in approximately
10% of patients (8). It is often due to increased pressure of the CSF on the pituitary
stalk and diminished dopamine inhibitory effect. Prolactin dynamics in PES may be
influenced by gonadal status, intracranial pressure, neurotransmitters, and stalk
integrity. Rarely, pituitary microadenomas causing acromegaly and Cushing’s disease
may be associated with empty sella. In the recent study by Himes et al. empty sella
was associated with an increased rate of MRI negative Cushing’s disease (9). Pituitary
compression causing a relative reduction in the volume of the pituitary for imaging is
a plausible cause for not detecting the tumor mass with MRI (9).
The prevalence of hypopituitarism in patients with PES is variable. In a study by
Guitelman et al. it was found in 28% of patients (9,10). Panhypopituitarism was
present in 40% of these patients, while partial or isolated hormone deficiencies were
diagnosed in 60% of hypopituitary patients (10). The most prevalent pituitary
deficiency was growth hormone deficiency.
In a pooled meta-analysis, which included 4 studies, the frequency of hypopituitarism
was 52% (11). Multiple pituitary hormone deficiencies were present in 30%, isolated
in 21% of patients with PES. Growth hormone and the gonadotropins were most
common isolated insufficiencies (11).
In the recent retrospective single-center study of 765 patients by Ekhzaimy et al. 79%
of PES was diagnosed incidentally on MRI. The majority of patients were evaluated
by general practitioners with suboptimal hormonal evaluation while only 20% were
referred to endocrinologists for hormonal evaluation (12).
Hormonal assessment is advocated in all patients with ES. In case of borderline
results or suspected isolated or partial insufficiency stimulatory tests are
recommended if clinically relevant for hormone replacement.
Other symptoms in patients with ES include: headache, visual and neurological
disturbances. In patients with intracranial hypertension these symptoms are more
common.

Neurological and Ophthalmic Dysfunction in PES

Headache is present in approximately 80% (3,6). In 20% of patients it may be
accompanied by visual disturbances, even papilledema in intracranial hypertension
(3,6).
Visual disturbances including worsening of visual acuity, blurred vision, diplopia,
defects of oculomotor nerve, and optical neuritis were also reported in patients with
PES. In case of benign intracranial hypertension ophthalmic echography and
computerized visual field with evoked potentials should be performed in consultation
with ophthalmologists. In case of chiasmal herniation into the empty sella with acute
visual deterioration, new neurosurgical techniques of chiasmal transsphenoidal
elevation are available (13, 14).
Study by Yilmaz et al. evaluated retinal optic nerve fiber thickness by optic coherence
tomography in asymptomatic patients with empty sella and healthy controls (14, 16).
Reduced values in asymptomatic patients provide valuable data for monitoring of
these patients (15).
Neurological disturbances: dizziness, syncope, cranial nerve disorders, convulsions
and depression were reported in approximately 40%of patients with PES (3, 6).
Rhinorrhea imposes the risk of meningitis.
Go to:

TREATMENT
In patients with increased idiopathic intracranial pressure osmotic diuretics or
acetazolamide (Diamox) are advocated. Weight loss may be efficient in obese and
overweight patients especially if accompanied by sleep apnea. Neurosurgical
techniques may be indicated for rhinorrhea and some symptomatic secondary causes
of empty sella syndrome with increased intracranial pressure and acute visual
disturbances. If diagnosed hypopituitarism should be replaced following the current
recommendations (16) and hyperprolactinemia treated with dopamine agonists.
Go to:

CONCLUSION
Primary empty sella can be heterogeneous in origin and presentations range from an
asymptomatic incidental radiological finding to endocrine and neuro-
ophthalmological manifestations. Female sex, multiple pregnancies, obesity, and
arterial hypertension are associated risk factors as well as the syndrome of benign
intracranial hypertension. Secondary empty sella is caused by various pathological
processes resulting in shrinkage of the pituitary gland. Routine hormonal status
assessment and regular follow-up are indicated in all patients since the prevalence of
pituitary dysfunction is significant.
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