Empty Sella Syndrome: Symptoms, Types, Causes and Treatment

Empty Sella Syndrome (ESS) is a fascinating and sometimes puzzling condition that has captured the attention of endocrinologists, neurologists, and radiologists alike. Often discovered incidentally on brain imaging, ESS can be an entirely silent finding or the underlying cause of a wide range of symptoms, from headaches to hormonal imbalances and vision problems. This article explores the complex world of Empty Sella Syndrome, guiding you through its symptoms, types, causes, and treatment options, all grounded in the latest research.

Symptoms of Empty Sella Syndrome

Empty Sella Syndrome can range from being asymptomatic to presenting with a diverse array of neurological, endocrine, and ophthalmological symptoms. Recognizing these symptoms is crucial for timely diagnosis and management, as some may signal underlying hormonal disturbances or increased intracranial pressure.

Symptom	Description	Frequency/Notes	Sources
Headache	Persistent or recurrent, sometimes severe	Most common symptom; may reflect raised ICP	1 2 3 5 7 9 12
Visual Changes	Visual field defects, decreased acuity, papilledema	May indicate optic chiasm compression or ICP	1 2 3 4 5 7 9 10 12 14
Endocrine Dysfunction	Hormonal imbalances (e.g. hypopituitarism, galactorrhea, menstrual irregularities, infertility)	Ranges from mild to severe; can affect any axis	3 5 6 7 11 13
CSF Rhinorrhea	Leakage of cerebrospinal fluid from the nose	Suggests communication between CSF and nasal cavity	1 4 7 8 12
Obesity	Often associated, particularly in women	Sometimes linked with raised ICP	1 3 7 9
Fatigue	Persistent tiredness, low energy	Non-specific but can be prominent	3 5
Psychiatric Symptoms	Mood or behavioral changes, psychosis	Rare; may occur with hormonal or neurologic involvement	3 5

Table 1: Key Symptoms

Headaches and Neurological Symptoms

Headache is the hallmark symptom of ESS and is reported as the most frequent complaint in symptomatic patients. The pain can be chronic and may be associated with signs of increased intracranial pressure, such as nausea or vomiting. In severe cases, neurological symptoms like psychosis or chronic fatigue have also been reported, suggesting involvement of adjacent brain structures or hormonal dysfunction 3 5 7 9 12.

Visual Disturbances

Visual symptoms arise when the optic chiasm or nearby structures are compressed or displaced. Patients may experience visual field defects (such as loss of peripheral vision), decreased visual acuity, or even papilledema (swelling of the optic disc). These symptoms are especially concerning, as they can progress to permanent vision loss if not addressed promptly 1 2 4 5 7 9 10 12 14.

Endocrine and Hormonal Abnormalities

The pituitary gland, which sits in the sella turcica, is the “master gland” of hormone regulation. In ESS, pituitary dysfunction can lead to a range of hormonal issues:

• Hypopituitarism: Reduced levels of one or more pituitary hormones, affecting growth, metabolism, reproduction, and stress response.
• Hyperprolactinemia: Elevated prolactin levels, leading to galactorrhea (milk production) and menstrual irregularities.
• Gonadal Dysfunction: Irregular or absent menstruation, infertility.
• Other Axis Involvement: Such as low thyroid (hypothyroidism), adrenal insufficiency, and growth hormone deficiency 3 5 6 7 11 13.

CSF Rhinorrhea

A rare but significant symptom, cerebrospinal fluid (CSF) rhinorrhea presents as clear fluid leakage from the nose. It indicates a defect in the sellar floor, allowing CSF to pass from the subarachnoid space into the nasal cavity. This can lead to complications like meningitis if not treated 1 4 7 8 12.

Other Symptoms

Obesity, chronic fatigue, and psychiatric/behavioral symptoms have been documented, particularly in women and those with longstanding disease. While not specific, these can be important clues when considered alongside other signs 3 5 7 9.

Types of Empty Sella Syndrome

ESS is not a one-size-fits-all condition. It is classified based on its origin, which influences both clinical presentation and management strategies.

Type	Defining Feature	Typical Scenario	Sources
Primary ESS	No prior pituitary disease; herniation of CSF	Often incidental, sometimes with symptoms	1 3 4 6 7 11 12
Secondary ESS	Follows pituitary surgery, radiation, or tumor	Known pituitary insult or treatment	1 2 11 13 14

Table 2: Types of ESS

Primary Empty Sella Syndrome (PES)

Primary ESS is characterized by the herniation of the subarachnoid space into the sella turcica due to an incompetent diaphragma sellae (the membrane covering the sella). This leads to flattening of the pituitary gland against the sellar walls. Most cases are found incidentally in imaging performed for unrelated reasons, and the majority of patients are asymptomatic. When symptoms do occur, they are often related to increased intracranial pressure or subtle pituitary hormone deficiencies 1 3 4 6 7 11 12.

Key points:

• No prior history of pituitary tumor, surgery, or irradiation.
• More common in middle-aged, obese women.
• Symptoms, if present, may include headaches, visual changes, hormonal disturbances, or CSF rhinorrhea.

Secondary Empty Sella Syndrome

Secondary ESS develops after an identifiable event or process that affects the pituitary gland, such as:

• Pituitary surgery (e.g., removal of a tumor)
• Radiation therapy
• Medical treatment of pituitary adenomas (e.g., dopamine agonists for prolactinomas)
• Pituitary apoplexy (sudden hemorrhage or infarction in the pituitary)

In these cases, the pituitary gland is damaged or reduced in volume, allowing CSF to fill the empty space. Symptoms are often related to the underlying cause and may include visual deterioration, hormonal deficits, or CSF leaks. Secondary ESS is more likely to present with significant clinical consequences compared to primary ESS 1 2 11 13 14.

Causes of Empty Sella Syndrome

Understanding the underlying causes of ESS is vital not only for diagnosis but also for determining the best approach to treatment and follow-up.

Cause	Mechanism	Notes	Sources
Diaphragm Defect	Incompetent diaphragma sellae, allows CSF herniation	Main cause in primary ESS	1 3 4 7 8 9 11 12
Raised ICP	Increased intracranial pressure pushes CSF into sella	Linked with obesity, pseudotumor cerebri	3 7 9 12
Pituitary Damage	Surgery, radiation, apoplexy, medical therapy	Main cause in secondary ESS	1 2 11 13 14
Congenital Factors	Developmental anomalies of sella or diaphragm	Rare, often in children	7 8 11
Tumors/Cysts	Intrasellar lesions displacing pituitary tissue	May mimic or cause ESS	2 8 10 13

Table 3: Underlying Causes

Structural Defects: The Diaphragma Sellae

The diaphragma sellae is a thin membrane that covers the sella turcica. In many cases of primary ESS, this membrane is congenitally weak or incomplete, allowing CSF to herniate downward and compress the pituitary gland. This structural defect is considered the most important anatomical factor in the development of primary ESS 1 3 4 7 8 9 11 12.

Increased Intracranial Pressure (ICP)

Elevated ICP—whether due to idiopathic intracranial hypertension (pseudotumor cerebri), obesity, or other causes—can force CSF into the sella turcica, especially if the diaphragma sellae is weak. This mechanism is particularly common in obese women and is associated with headaches, visual symptoms, and sometimes hormonal changes 3 7 9 12.

Pituitary Injury or Loss

Secondary ESS results from direct damage to the pituitary gland, most frequently after:

• Surgical removal of pituitary tumors
• Radiation therapy for pituitary or neighboring brain tumors
• Medical therapy, especially dopamine agonists for prolactinomas, which can shrink the tumor and gland
• Pituitary apoplexy (hemorrhagic or ischemic events in the pituitary)

The loss or shrinkage of pituitary tissue creates a void that is filled by CSF, leading to the “empty” appearance on imaging 1 2 11 13 14.

Other Contributing Factors

Less commonly, congenital abnormalities or intrasellar cysts and tumors may contribute to ESS by altering the structure of the sella or displacing the pituitary gland 7 8 10 13.

Treatment of Empty Sella Syndrome

Management of ESS depends on whether the condition is symptomatic or asymptomatic, as well as the nature and severity of the symptoms. The approach is highly individualized and often multidisciplinary.

Approach	Indication	Details/Goals	Sources
Observation	Asymptomatic/incidental finding	No treatment; periodic follow-up	1 4 6 11
Hormone Therapy	Endocrine dysfunction	Replace deficient hormones	6 7 11 13
Surgery	CSF leak, visual deterioration, severe ICP	Repair sellar floor, CSF shunt, chiasmapexy	1 4 7 12 14
Multidisciplinary Care	Complex/symptomatic cases	Involve endocrinology, neurology, ophthalmology, neurosurgery	7 11 14

Table 4: Treatment Strategies

Observation and Monitoring

For the majority of patients with incidentally discovered, asymptomatic ESS, no treatment is needed. Regular follow-up is recommended to monitor for the development of hormonal deficits or other complications 1 4 6 11.

Hormonal Replacement Therapy

If pituitary hormone deficiencies are identified, tailored hormone replacement is essential. This may include:

• Corticosteroids for adrenal insufficiency
• Thyroid hormone for hypothyroidism
• Sex hormones for gonadal dysfunction
• Growth hormone if indicated

Periodic evaluation of pituitary function is important, as hormonal needs may change over time 6 7 11 13.

Surgical Intervention

Surgery is reserved for specific complications:

• CSF Rhinorrhea: Surgical repair of the sellar floor to prevent ongoing CSF leakage and reduce risk of meningitis.
• Visual Deterioration: Chiasmapexy (surgical elevation of the optic chiasm) may be performed if the optic chiasm is herniated into the sella, sometimes using autologous cartilage or bone as support materials 1 4 7 12 14.
• Severe Intracranial Hypertension: CSF diversion procedures, such as ventriculoperitoneal shunt, can be performed to relieve pressure, especially in cases with neurologic compromise 12.

Multidisciplinary Management

Given the complexity and variability of ESS, a multidisciplinary approach is often best. Endocrinologists, neurologists, neurosurgeons, and ophthalmologists may all play a role in the diagnosis, treatment, and follow-up of affected patients 7 11 14.

Conclusion

Empty Sella Syndrome is a multifaceted condition that ranges from a silent radiologic finding to a symptomatic disorder with significant neurological, endocrine, and ophthalmological implications. Early recognition and tailored management are key to optimizing patient outcomes.

Key Points:

• ESS can be asymptomatic or present with headaches, visual changes, hormonal imbalances, CSF rhinorrhea, or psychiatric symptoms.
• Primary ESS is due to anatomical defects and increased intracranial pressure; secondary ESS follows pituitary damage.
• Diagnosis is often made via MRI or CT, with pituitary hormone testing in symptomatic cases.
• Treatment ranges from observation to hormone therapy and surgery, depending on symptoms and complications.
• A multidisciplinary approach is essential for complex cases.

Recognizing and understanding ESS enables clinicians and patients alike to address both the visible and hidden consequences of this intriguing syndrome.