Introduction

Empty Sella Syndrome (ESS) is a condition that affects the pituitary gland, a small kidney-bean-sized gland at the base of the brain that controls many hormones.¹ 

The pituitary gland is particularly important for its role in many bodily functions; it secretes hormones that help regulate growth, maintain healthy blood pressure, manage energy levels, control the functions of the reproductive organs, and influence the activity of the thyroid gland, which has other important roles such as thermoregulation.^2,3

Normally, the pituitary gland fills a spot called the sella turcica (known as ‘Turkish saddle’ in Latin), which holds it securely in place. When this cavity looks empty or is filled with cerebrospinal fluid (fluid found in the brain and spinal cord) instead of the normal gland tissue, it is called an empty sella.⁴

ESS can be present without showing symptoms and may be found accidentally, or it can be associated with hormonal imbalances, and sometimes neurological or mental health problems. 

ESS is considered rare; however, recent increases in the number of people with this condition is likely due to the more recent development of improved imaging techniques. Studies have found ESS in about 6-20% of autopsies and up to 38% of brain scans, more commonly found in MRI than CT scans. Empty sella is more than five times more common in women than in men, and is also seen more often in people with obesity between the ages of 40 and 60. About 40% of patients with this condition have pre-existing hormonal problems.⁴ 

This article will explore the types of ESS, how it is diagnosed, and the cognitive and psychiatric symptoms associated with it.

Types of ESS⁵

There are two types of ESS: primary ESS and secondary ESS.

These two types of ESS differ in their cause; however, they share some general symptoms:

Other general symptoms of both PES and SES, in addition to those mentioned above, include:

• Headaches
• Vision problems, like trouble seeing or loss of side vision

Primary ESS

Primary ESS (PES) is diagnosed when no obvious reason for ESS can be found. It is most commonly seen in women who have had several childbirths or in people who are overweight. 

Some people with PES may also have higher levels of prolactin, a hormone that influences how the ovaries and testes work. Roughly half of the men with PES will also have low testosterone levels, a condition known as central hypogonadism. Some patients may also have lower levels of other hormones produced by the pituitary gland.

Secondary ESS

Secondary ESS (SES) occurs when the pituitary gland becomes smaller or shrinks due to non-hormone-related factors. This can happen due to things like a tumour, surgery, or radiation treatment. When this occurs, the gland may be damaged or even disappear on scans. 

People with secondary ESS often have problems with the hormones that the pituitary normally produces. For example, about half of women with this condition will have low levels of growth hormone and hormones involved in the body's stress response. This disrupted hormone functionality can lead to symptoms such as: ⁴

• Missing periods or stopping completely
• Difficulty getting pregnant
• Feeling very tired
• Having trouble managing stress and infections

ESS in children

Although it is quite uncommon, ESS can sometimes happen in children. In some cases, children are born with issues in the area where the pituitary gland sits.

Sometimes, ESS in children can happen later after birth because of injuries, tumours, cysts, or long-term illnesses. Many children with ESS do not show any noticeable symptoms. However, some may experience early signs of puberty, slower growth, hormone problems, or vision problems.⁵

Many people think of ESS primarily in terms of hormone issues, given that the pituitary gland produces important hormones that affect growth, metabolism, reproduction, and other bodily functions. However, research has shown that some patients with ESS also experience mental and cognitive (thinking and memory) symptoms.⁶

How do empty sella syndrome and cognitive or psychiatric symptoms connect?

Cognitive symptoms are problems related to thinking. These include difficulties with memory, concentration, attention, quick thinking, problem solving, and understanding complex ideas.⁷

Psychiatric symptoms in mood disorders include experiences like depression, anxiety, mood swings, or other emotional disturbances.⁸ 

In patients with ESS, these symptoms can sometimes be present along with or independently of hormonal problems.

While the exact link between these symptoms and ESS is not yet fully understood, several theories exist:

Hormonal imbalances 

The pituitary controls other glands (like the thyroid and adrenal glands). If ESS causes hormone levels to be too low or too high, it can affect brain functions. Hormones such as cortisol, thyroid hormones, and sex hormones influence mood, energy levels, and cognitive functions. Not having the right hormone balance can lead to forgetfulness, sluggish thinking, depression, or anxiety.⁹ 

Structural changes in the brain

Sometimes, the ESS changes the pressure in the brain, which can cause subtle structural differences. These changes may influence how well certain parts of the brain work, particularly those involved in thinking and emotion.¹⁰ 

Secondary effects

If ESS causes symptoms like difficulties with sleep or chronic fatigue, these can indirectly affect mental functioning and mood. When you have sleep problems, your body cannot sufficiently rest and repair your brain, mind, and body, which will negatively affect your mental health.¹¹ 

Who gets cognitive or psychiatric symptoms in ESS?

Not everyone with ESS experiences these symptoms. They are more likely if someone has;¹²

• Significant hormone irregularities
• Pre-existing mental health issues
• Abnormalities in brain structure 
• Other health problems affecting the brain

What do patients usually experience?

Some common cognitive symptoms include:¹³

• Forgetfulness or memory lapses
• Difficulty concentrating
• Feeling mentally slow or “foggy”
• Trouble with learning new information or complex tasks

Psychiatric symptoms often include:¹⁴

• Depression
• Anxiety or nervousness
• Mood swings
• Irritability or emotional instability
• Schizophrenia

However, the severity of these symptoms varies widely among individuals. Some may have mild symptoms that don't interfere much with daily life, while others may find their mental health significantly affected.¹⁵

Diagnosis of ESS

ESS is typically diagnosed using various imaging techniques, often through the use of MRI (magnetic resonance imaging) or CT (computed tomography) scans, when requested for other suspected medical reasons.¹ 

To figure out whether someone’s cognitive or psychiatric symptoms are related to ESS, doctors may perform:¹⁰

• Imaging scans, such as MRI, to confirm if the sella is empty or partially empty
• Blood tests: to check the levels of hormones controlled by the pituitary gland
• Neuropsychological assessments: tests that measure memory, attention, problem-solving, and other mental functions
• Psychiatric evaluation: to diagnose depression, anxiety, or other mental health conditions

A comprehensive approach ensures that other causes of psychiatric symptoms, like primary mental health disorders or other neurological issues, are considered.¹⁶

Treatment approaches

Addressing cognitive and psychiatric symptoms in ESS involves several approaches.

Hormone replacement therapy 

If blood tests show hormonal deficiencies, doctors may prescribe hormones such as thyroid hormone, cortisol, or sex hormones. Restoring hormones to normal levels can improve mood, energy, and cognitive functions.¹⁷

Psychiatric treatments¹⁷

• Counselling or psychotherapy: helps patients cope with emotional symptoms
• Medications: antidepressants or anti-anxiety drugs may be prescribed if needed

Lifestyle changes¹⁸

• Regular physical activity
• Adequate sleep
• Healthy diet
• Stress management techniques 

These treatment approaches can support overall brain health and improve mental symptoms.

Prognosis and outcomes

One study (conducted on female patients) suggests that patients may experience improvement in their symptoms after addressing hormonal imbalances and receiving supportive mental health care. How much someone improves depends on how serious their symptoms were at the start, how quickly they begin treatment, and other personal factors.¹⁸

Some patients may continue to have ongoing cognitive or psychiatric symptoms despite treatment, requiring ongoing management and support.¹⁹

Summary

Empty Sella Syndrome (ESS) is a condition where the pituitary gland appears shrunken or absent in the sella turcica, often filled with cerebrospinal fluid. It can occur as primary ESS (PES) without a clear cause, often in obese women with multiple childbirths, or as secondary ESS (SES) due to tumours, surgery, or radiation. While ESS is often asymptomatic, it may cause hormonal imbalances that disrupt growth, reproduction, stress response, and energy regulation.

Beyond hormonal issues, ESS can also lead to cognitive symptoms (memory problems, poor concentration, mental “fog”) and psychiatric symptoms (depression, anxiety, mood swings, irritability, and rarely schizophrenia). These arise from hormonal dysregulation, brain structural changes, or indirect effects like sleep problems and fatigue.

Diagnosis relies on MRI/CT imaging, hormone testing, and mental health assessments. Treatment focuses on hormone replacement therapy, psychiatric care (medication, psychotherapy), and lifestyle changes (exercise, diet, sleep, stress management). Prognosis varies—many improve with treatment, though some experience persistent symptoms requiring ongoing support.