What is empty sella syndrome?

Empty Sella Syndrome (ESS), also commonly known as arachnoidocele, is an anatomical condition that affects a part of the brain, specifically a saddle-shaped gap in the sphenoid bone within the skull called the sella turcica.¹

Under normal circumstances, the pituitary gland is a small, bean-like structure that completely fills the sella turcica. However, when ESS is present, it causes an unusual compression abnormality of the pituitary gland. In turn, this is often confirmed through imaging studies, such as MRI or CT scans, which show an empty cavity in the sella, hence giving this condition its name: Empty Sella Syndrome.

ESS is classified into two types: primary ESS, where no identifiable cause leads to pituitary shrinkage, and secondary ESS, which results from an underlying factor such as surgery, radiation therapy, or injury sustained while treating a nearby brain tumour. This syndrome is more common in females, especially those who have given birth to multiple children, than in males, and it also affects obese people.

How does the pituitary gland play a role?

The pituitary is often regarded as the “master gland” due to its important role in secreting various hormones daily into our bloodstream, with a significant impact on the body’s physiology. The gland’s function is strictly regulated and controlled by the hypothalamus, a structure slightly above the gland that detects functional changes throughout the body to maintain homeostasis.

There are two parts to the master gland: an anterior and a posterior side, which secrete vastly different sets of hormones. The anterior pituitary is responsible for some of the more well-known hormones, such as growth hormone, thyroid-stimulating hormone and follicle-stimulating hormone. The posterior, meanwhile, only releases oxytocin and vasopressin, which we will discuss later in the article.

Without doubt, the pituitary gland could be regarded as one of the most important structures in the human body. Due to the diverse range of hormonal factors it controls, it has a major influence on the growth of the body, even the 206 bones we have. Its influence also extends to every aspect of the body, ranging from energy levels via metabolism to reproduction and even the stress levels we experience.

How do I know if I am a victim of ESS?

Fortunately, with the advancement of technology and methodology, we can now detect whether pituitary hormone deficiencies or dysfunction are present. As mentioned above, advanced imaging techniques such as MRI or CT scans can directly show whether the pituitary gland is present within the sella turcica or whether some form of shrinkage has occurred.

Besides imaging, a general guide for diagnosing this syndrome before treatment decisions involves checking hormone levels. As previously mentioned, the pituitary plays a role in controlling various hormones, so hormonal disruptions in factors uniquely released by the gland can often indicate signs of an issue.

Why the strange correlation with females?

Before delving into the testing, diagnosis, and possible treatments available, we need to understand the epidemiology of ESS and its correlation with its unique mechanism of action. The disorder, as mentioned above, is much more prevalent in obese females, with almost a 5:1 ratio to males.

Females who have given birth to multiple children are often more susceptible to the syndrome, as hormone levels shift dramatically during pregnancy. There is strong evidence linking this disruption to increased lipid storage through various mechanisms, such as fatigue and cravings, which often persist even after parturition.

Diving deeper into ESS with a hypothesis

The hypothesised explanation for why ESS is more prevalent in obese individuals could be attributed to exponentially increased arterial pressure. A higher body mass usually indicates that either more cells or tissue have developed, or that an excessive amount of lipid has accumulated. This exerts more compression on the many branching blood vessels, causing a decrease in their diameter and ultimately spiking the pressure within the vessels. This risky condition is known as Idiopathic Intracranial Hypertension (IIH) and is commonly associated with obesity.²

ESS, although primarily just a structural defect, has been shown to weaken the diaphragm sellae, a membrane barrier that separates the sella cavity from the subarachnoid space in the brain. Combined with what we know so far, this means that high central pressure could indirectly alter the flow dynamics and pressure of cerebrospinal fluid (CSF), the fluid that surrounds the brain, exerting a stronger force on the sella. Therefore, chronic obesity or high intracranial pressure could lead to slow, long-term compression of the pituitary gland, which contributes to the partial space seen in primary ESS.

This principle can also be applied to pituitary tumours, where an uncontrolled division of cells leads to a drastically increased, localised mass. Surgical interventions are often used to treat such underlying conditions but carry a notable risk of further damaging the gland, which can result in secondary ESS.

Testing on the master gland

Currently, pituitary function testing is widely regarded as the best method for checking the health of the pituitary gland. It comprises a series of functional assessments that measure baseline and post-medication hormone levels in the bloodstream.

Static test

To test for the baseline, or static, hormone level, doctors often take blood samples before 8am, since pituitary hormones are secreted according to the circadian rhythm, and ask you not to consume any food for at least eight hours beforehand.³

Anterior pituitary axes

Within the anterior pituitary is a protein hormone called adrenocorticotrophic hormone (ACTH), which plays an important role in regulating stress levels and is present in the blood at its highest concentration around 8am. Similarly, thyroid-stimulating hormone and the gonadotrophins, also peptide or protein hormones, are tested using the same method. Testosterone is commonly tested in male patients, whereas luteinising hormone and follicle-stimulating hormone are tested in women. Doctors can test for all of these basal levels by adding antibodies, special protein structures with binding sites that are complementary to each hormone’s individual structure.

Growth hormone, on the other hand, uses IGF-1 as its stable marker, but the same principle applies, since GH itself fluctuates. Prolactin requires only a single fasting blood test, with the added condition of avoiding stress or nipple stimulation beforehand.

Posterior pituitary axes

There are only two hormones secreted by the posterior part of the master gland, namely vasopressin and oxytocin. Vasopressin, also known as antidiuretic hormone, regulates urine volume. It is tested more commonly than oxytocin, but the approach is also more indirect due to its instability and inconsistency in blood samples. Doctors test it via plasma or urine osmolality.

Dynamic testing

Currently, ACTH stimulation remains the most popular dynamic test, compared with gonadotrophin or thyroid-releasing hormone stimulation tests, which are used more rarely.⁴

Most of the time, doctors will only recommend it if you have already conducted a static test and your cortisol level is very low. Essentially, ACTH, either naturally derived or synthesised, is injected into the muscle to test adrenal function. Multiple blood samples are then taken at intervals to check for an increase or decrease in concentration. The insulin tolerance test also tests for ACTH; it involves injecting insulin and assessing the reserve level. Insulin is a hormone that lowers glucose levels, which causes ACTH to spike in response.

Neuroimaging

The main structural tests for neuroimaging are the MRI and CT scan, which directly detect any pituitary abnormalities. Visual field testing can also be used to check for optic chiasm compression, but it is much less common now that brain imaging is readily available.

Interpretation and management

Under normal circumstances, where the pituitary gland is partially compressed but still functions without issue, no hormone replacement is needed, although it can be monitored over time if there are any concerns.

For partial or full panhypopituitarism, this means there could be selective or multiple hormone deficiencies, respectively.⁵

For such more concerning conditions, tailored hormone replacement can usually be done based on your hormone profile to avoid medical complications. Of course, referrals can also be made by doctors for further testing depending on the results. Below are some examples:

• Endocrinology referral: For abnormal or unclear results
• Hormone replacement therapy: Cortisol, thyroid hormone, sex steroids, GH
• Monitoring and follow-up: Periodic reassessment, especially if symptoms evolve

Summary

ESS is a rare condition that involves the pituitary gland and the sella turcica. It results from compression of the master gland that resides within the gap, leading to hormonal disruptions. While the disorder sounds severe, it is most of the time not life-threatening, though it can pose an inconvenience to an individual’s daily life. This is due to the pituitary being perhaps the most significant structure in the body, secreting a diverse range of hormones, such as growth hormone and thyroid-stimulating hormone, that are responsible for the body’s development during adolescence.

Pituitary gland testing is currently the best method used to identify early onset of the syndrome. These are usually categorised into static or dynamic testing, but in both cases the doctor typically extracts blood samples, with the only notable difference being that dynamic testing uses medicines to stimulate a response in certain hormones. Certain, more advanced, neuroimaging techniques such as MRI or CT scan also provide the most accurate diagnosis through more direct structural visualisation.

Overall, there is no direct cure for this syndrome, and it can only be monitored closely to prevent worsening symptoms. While personal monitoring of your daily habits can help ensure the most successful outcome from treatment in rare cases, you should also keep a relaxed mind, as it is, again, not a severe disorder that will lead to any form of injury.