Empty sella syndrome (ESS) is an uncommon but increasingly recognised condition. It is distinguished by a space on a brain scan, which may entail further hormonal and brain-related issues. Within this condition, people may unknowingly have ESS for years with no symptoms at all, while others may experience serious hormone imbalances and require urgent treatment. For most people, they may only discover they have this condition when receiving a brain scan for an unrelated reason. This article presents real case studies to illustrate the wide range of symptoms and outcomes associated with ESS. 

What Is Empty Sella Syndrome?

Empty sella syndrome (ESS), also called arachnoidocele, is a condition where a hollow section of the skull that protects the pituitary gland (the hormone regulator), called the sella turcica, appears empty on a brain scan. This section is usually filled with cerebrospinal fluid (CSF), a clear liquid that cushions the brain.¹

This occurs when the sella membrane, called the diaphragmatic sellae, allows the CSF to position downwards and push on the pituitary gland. The gland can become flattened and can stretch the pituitary stalk (connecting the pituitary gland to the hypothalamus). This can lead to the development of hormone deficiencies.¹

Types of Empty Sella Syndrome 

There are two main forms of ESS: Primary ESS and Secondary ESS.¹

Primary ESS

This type of ESS is caused by the combination of a weakness in the membrane covering the pituitary gland (diaphragma sellae) and increased CSF pressure.¹ 

CSF can then leak into the sella turcica, causing the pituitary gland to compress against the walls of the sella gradually. This can either flatten the pituitary gland or enlarge the sella turcica, giving the impression of an empty sella. Primary ESS is usually seen in people assigned female at birth, who are middle-aged, overweight, or have high blood pressure.²

Secondary ESS

This type of ESS develops after an event that shrinks or damages the pituitary. This can be after surgery, inflammation, radiation therapy, head injury, or severe internal bleeding. ¹ Sometimes, the pituitary tumour can shrink by itself without treatment.²

How common is ESS?

ESS is uncommon, but is found in around 5.5-12% of autopsy studies and arises in around 12% of brain scans. Primary ESS is found in up to 20% of cases, whilst being more common among people assigned female at birth, around a 4 to 5:1 ratio. ESS is frequently found in those who already have idiopathic intracranial hypertension, which is around 70% of cases.¹

What are the signs and symptoms of ESS?

Due to the pituitary gland controlling many important hormones, Empty sella syndrome can have several different effects on the body. The symptoms can develop from hormonal changes (endocrine effects) or due to pressure around the eyes and inside the skull (ophthalmologic and neurologic effects).³

Endocrine (hormonal) symptoms  

The pituitary gland controls functions surrounding growth, stress, metabolism, and reproduction. Therefore, dysfunction may include problems such as:³

• Weakness 
• Fatigue
• Menstrual changes
• Reduced libido
• Abnormal weight fluctuations
• Infertility 
• Feeling unusually hot or cold³

These symptoms occur due to the reduction of certain pituitary hormones. In ESS, the most common hormone deficiencies are:³

• Central hypothyroidism (low thyroid hormone, even with normal levels of TSH)
• Secondary adrenal insufficiency (low cortisol production)
• Hypogonadotropic hypogonadism (reduced testosterone or oestrogen)
• Growth hormone deficiency³

Ophthalmologic (eye) and neurologic (brain) symptoms 

Due to the location of the sella turcica being just below the brain and optic nerves, ESS can manifest as pressure-related symptoms, including:

• Persistent headaches
• Vision changes (such as blurred vision, double vision, or involuntary eye movements)
• Nausea or temporary vision loss (linked to high intracranial pressure)
• Sudden cerebrospinal fluid leak through the nose (CSF rhinorrhoea)³

No symptoms 

Many people with an empty sella have no complications or symptoms, with normal hormone test results. Sometimes doctors may call this ‘isolated empty sella’ rather than ESS. In these cases, it is very unlikely that an isolated empty sella will progress to ESS or have a change in future scans. When people experience no symptoms and hormone levels are normal, no treatment is required.³ 

Case Studies of Varied Presentations

Case 1 - Primary ESS

A 49-year-old woman with obesity presented symptoms of headaches, blurred vision, tiredness, and cramps on her left side for one month. Her blood tests showed central hypothyroidism (underactive thyroid gland), but she had normal functioning of other pituitary hormones. A CT scan was undertaken and confirmed empty sella syndrome, showing a CSF-filled sella turcica and flattened pituitary tissue.⁴

She was administered L-thyroxine (50 μg daily), which normalised her thyroid levels and energy, and relieved her muscle symptoms. Case 1 shows primary ESS, which can be treated effectively with minor replacement therapy.⁴ 

Case 2 - Secondary ESS 

A 54-year-old man from China presented with a fever, headache, backache, dizziness, and little urine for five days. Through blood tests, it was confirmed he had haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus. He then entered the phase of heavy urination, of around 10 litres in one day.⁵

Hormone tests confirmed underactivity of the entire pituitary gland (panhypopituitarism), including low levels of: cortisol, growth hormone, thyroid hormone and testosterone.  MRI also showed CSF filling the sella turcica and a thin-rimmed pituitary tissue. This confirmed secondary ESS occurring during HFRS.⁵

The patient was administered hydrocortisone, testosterone replacement therapy, and L-thyroxine. Within a month, his fatigue, urine, and hormone levels returned to normal. Case 2 shows secondary ESS triggered by HFRS, which responded well to hormone replacement therapy.⁵

Case 3 - Primary ESS

A man over 90 years old had a very compressed pituitary gland due to the CSF pushing down on a weakened diaphragma sellae. Pituitary tissue examinations showed normal cell structure and cell types, even with the flattening.⁶

This case shows that long periods of time (over decades) can allow the gland to adapt, explaining the asymptomatic nature of primary ESS. Treatment is only required if symptoms arise, with surgery for CSF leak complications, hormone replacement for deficiencies, and weight loss for intracranial pressure-induced headaches/ visual issues.⁶

These cases show examples of the varied presentations and outcomes of ESS, ranging from being easily treatable, requiring several hormone therapies, to asymptomatic cases where no treatment is needed. 

How is ESS diagnosed?

After undertaking a brain scan, if the result shows an empty sella, they will be checked for ESS. This is because an empty sella may have hidden hormone and nerve issues. The evaluation involves:³

• Detailed medical history - this is to identify risk factors like previous pituitary disorders, obesity, hormone imbalances, and idiopathic intracranial hypertension
• Physical examination - to check for optic nerve swelling, thyroid gland changes, small testicles, or loss of visual fields 
• Blood hormone testing - assessing the functioning of important pituitary cell types (gonadotroph, somatotroph, lactotroph, corticotroph, and thyrotroph)³
• Lumbar puncture - (when a thin needle is inserted between the lower bones of the spine), only for when additional information is needed to make the diagnosis 
• Eye examination - to examine the retina and assess vision loss⁷ 

Imaging tests can then be conducted to confirm the diagnosis. The most common test is Magnetic resonance imaging (MRI) of the pituitary and surrounding areas. If an MRI is not possible, a Computed Tomography (CT) scan can be done instead.¹

Common Scan Results

• Enlarged sella turcica 
• Flattened pituitary gland 
• Cerebrospinal fluid (CSF) fills the space¹

Blood hormone tests are important for every person, as low cortisol levels can cause dangerously low blood sodium (hyponatraemia).¹

What is the management and treatment?

Treatment is not required for cases of ESS with no symptoms. However, if symptoms develop, treatment aims to replace missing hormones and is usually not complicated, leading to positive outcomes.¹

• Hydrocortisone (cortisol replacement) is the first replacement to prevent adrenal issues
• Thyroid hormone (levothyroxine) is used when cortisol levels are stable 
• Sex hormone replacement (testosterone, oestrogen, or progesterone) can be administered later if required¹

Neurologic (Brain) Treatment 

If ESS is causing symptoms of vision issues, severe headaches, or CSF leakage, surgery may be required for pressure relief and to protect the eyes and the brain.³

What is the long-term outlook?

ESS is usually a long-term condition requiring regular monitoring and personalised therapy. Risks of further complications are dependent on how well hormonal or neurological problems are detected and subsequently treated.³

Deficiencies in pituitary hormones are linked to an increased risk of early death or illness. However, with prompt hormone replacement and, when needed, surgery, most people can sustain good long-term control of symptoms.³

FAQs

How common is empty sella syndrome?

ESS is uncommon, but not rare. It is seen in around 12% of brain scans.¹

Is it life-threatening?

ESS is rarely dangerous, and with proper monitoring and treatment, people maintain good long-term symptom control. However, risks can arise if important pituitary hormones are severely low.³

When is empty sella syndrome typically diagnosed?

The wide majority of ESS cases are asymptomatic and are usually only detected if brain scans are taken for other reasons. If there are no ESS symptoms, treatment is not required.²

Summary

Empty sella syndrome (ESS) is a long-term condition that varies vastly in its presentation and management. ESS presents in two forms: primary ESS (developed from weakness in the pituitary gland protective membrane and increased cerebrospinal fluid pressure) and secondary ESS (developed after injury). Some people remain asymptomatic and may never require any treatment, while others may develop deficiencies in hormone levels or show neurological symptoms. In these cases, most people will need hormone replacement or, in rare cases, surgery. Three unique cases were discussed in this article, showing the varied presentations of ESS, from mild primary ESS to secondary ESS after a viral infection to a long-term primary ESS presenting with no symptoms.