Empty Sella

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Continuing Education Activity

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. Regarding pathophysiology and etiology, empty sella syndrome (ESS) subdivides into two categories: primary empty sella syndrome (PES) and secondary empty sella syndrome (SES). This activity articulates how to properly evaluate this condition and highlights the role of the interprofessional team in caring for patients with this empty sella syndrome.


  • 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.


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 regarding 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.


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 article 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 the resultant herniation of CSF into the sella turcica.[1] 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.


Empty sella syndrome is considered 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.[2] Some reports note an even higher incidence in clinical practice, with estimates of up to 35%.[2] 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.[2][3] Although more common in women, pituitary hormonal dysfunction appears to occur at higher rates in men with empty sella.


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, small vessel disease, and temporary expansion followed by regression of the pituitary gland.[4]

Incompetent diaphragma sellae has been the finding in the vast majority of PES in 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.[5] 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.[6]

The last proposed mechanism causing empty sella involves an initial enlargement of the pituitary gland followed by a later decrease in gland size, creating an empty space where CSF can accumulate.[7] Examples 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 treating 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.[3]

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 a lack of evidence to support ESS as the cause of the headache. Many experts believe that the association exists because the headache of any unrelated cause prompted imaging of the head, leading to the incidental discovery of the empty sella. Other authors consider the possibility that increased intracranial pressure and possible herniation cause 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.[8]

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

In recent case reports, there have been rare patient presentations with unusual symptoms and signs, like hyponatremia, acromegaly, and mental problems like dementia.[9][10]


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.[11][12][13] 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.[3][14] Hyperprolactinemia is present in 10 to 17% of cases and may result from a microprolactinoma or functional hyperprolactinemia.[2][14]

Growth hormone deficiency presents in 4 to 60% of cases, but its clinical significance in adults is unclear.[2][11] 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.[11]

The following labs are necessary for the evaluation of pituitary function in any patient found to have empty sella[15]:

  • Adrenal axis: Early morning fasting cortisol levels are a screening option for adrenocorticotropin (ACTH) deficiency, and overtly low cortisol levels less than 3.0 mcg/dL are consistent with adrenal insufficiency.[16] 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 the 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. A testosterone level with simultaneous LH and FSH levels should be obtained in men. 

  • Prolactin (PRL): PRL levels should be obtained. Hyperprolactinemia is much more common than PRL deficiency. PRL elevations can be seen in many conditions unrelated to ESS (e.g., 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.[11] 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 clinician 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. In rare case reports, hyponatremia was the presenting sign of empty sella.[9]

  • 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 toward the hormone derangements present.

Differential Diagnosis

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


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.


As noted above, possible complications of empty sella include the development of partial or complete hypopituitarism or hormone hyperfunctioning. Additionally, there is an association of worse outcomes for patients undergoing pituitary surgery with known primary empty sella (e.g., Cushing disease) as well as radiographic disruption of the pituitary stalk.[17][18]

Deterrence and Patient Education

Patients can do nothing in particular to avoid this phenomenon, but they should be aware of the need to evaluate hormone levels at diagnosis. No additional testing is required if initial hormone levels are within normal limits.

Enhancing Healthcare Team Outcomes

Empty sella syndrome is a rare entity that is usually found incidentally during the evaluation of headaches 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 is 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
Empty sella MRI
Image courtesy S Bhimji MD
Article Details

Article Author

Peter Ucciferro

Article Editor:

Catherine Anastasopoulou


10/7/2022 6:59:10 PM



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