What is empty sella syndrome?

What is Empty Sella Syndrome?

Empty sella syndrome is a condition where cerebrospinal fluid herniates into the sella turcica through a deficient or absent sellar diaphragm, compressing and flattening the pituitary gland against the floor of the sella, which appears "empty" on imaging despite the pituitary gland still being present. 1

Pathophysiology and Classification

Empty sella occurs when the subarachnoid space herniates into the sella turcica, causing variable degrees of pituitary gland flattening. 2 The condition is classified into two distinct forms:

Primary Empty Sella

• Develops without any prior pituitary pathology, surgery, radiation, or pharmacologic treatment of the sellar region 2
• Results from pulsation of cerebrospinal fluid through a developmental or acquired dehiscence of the diaphragm sella 1
• May be associated with idiopathic intracranial hypertension, particularly in patients presenting with headache and papilledema 3
• Some evidence suggests it may represent a stage in the spontaneous course of pituitary adenomas that have undergone necrosis 4

Secondary Empty Sella

• Occurs after treatment of pituitary tumors through neurosurgery, medications, or radiotherapy 2
• Can develop following spontaneous necrosis (ischemia or hemorrhage) of pituitary adenomas 2
• May result from pituitary infectious processes, autoimmune diseases, or brain trauma 2

Clinical Presentation

Asymptomatic Empty Sella

• The majority of cases represent only a radiological finding without clinical manifestations 5, 2
• Incidence reaches approximately 12% on neuroimaging studies and up to 35% in clinical practice 5
• Most patients never develop symptoms and have a good prognosis with little impact on quality of life 6

Empty Sella Syndrome

• Defined by the presence of pituitary hormonal dysfunction and/or neurological symptoms in addition to the radiographic finding 6, 2
• Approximately 30% of patients with empty sella demonstrate some degree of hypopituitarism upon testing, though most remain asymptomatic 3, 7
• Endocrine pituitary disorders (at least one hormone deficit) occur in 19-40% of patients 5

Key symptoms requiring urgent evaluation include: 3

• Visual changes or visual field defects
• Signs of hormonal deficiencies (fatigue, cold intolerance, sexual dysfunction)
• Headache with features of increased intracranial pressure
• CSF rhinorrhea

Diagnostic Approach

Imaging

MRI using high-resolution pituitary protocols is the gold standard for diagnosis and can confirm empty sella even without IV contrast. 1, 3, 5 The pituitary gland appears flattened with cerebrospinal fluid filling the sella turcica. 6

• CT has limited utility and is insensitive compared to MRI for detecting pituitary pathology 3
• Plain radiography is insensitive and nonspecific for evaluating sellar pathology 1

Mandatory Hormonal Evaluation

All patients with empty sella should undergo comprehensive hormonal screening regardless of symptoms, as hormone deficiencies may affect up to 48% of cases. 3 The hormonal panel should include:

• Thyroid function tests (TSH, free T4) - deficiencies seen in up to 48% of cases 7
• Morning cortisol and ACTH (adrenal axis assessment) 7
• Sex hormones (testosterone in males, estradiol in females, FSH, LH) 7
• Prolactin levels - elevated in approximately 28% of cases 7
• IGF-1 for growth hormone axis evaluation 8

Management Strategy

Initial Assessment

• Perform comprehensive hormonal screening on all patients with empty sella, even if asymptomatic 3
• Obtain ophthalmology evaluation if visual symptoms are present or concerns about increased intracranial pressure exist 3, 6
• Refer to endocrinology if any hormonal abnormalities are detected 3, 7

Follow-Up

• If no alterations are detected initially, careful reevaluation at 24-36 months is suggested due to low risk of progression 5
• Monitor for development of symptoms over time 6

Treatment of Associated Conditions

• If associated with idiopathic intracranial hypertension, weight loss is the primary treatment, with surgical CSF diversion reserved for imminent visual loss 3
• Hormone replacement therapy as indicated for specific deficiencies 2
• Surgical treatment (transsphenoidal filling of the sella) is rarely indicated, primarily for progressive visual field defects or CSF rhinorrhea 9

Critical Clinical Pitfalls

Do not attribute headache directly to empty sella, as it is usually an incidental finding unrelated to headache symptoms. 3, 7 Consider more common headache etiologies first.

Do not overlook idiopathic intracranial hypertension in patients with headache and empty sella, as partially empty sella is a typical neuroimaging feature of raised intracranial pressure and represents a distinct clinical entity requiring specific management. 3

Do not skip hormonal screening even in asymptomatic patients, as affected-axis rates often exceed 10% and may reach 50%, with significant clinical implications if missed. 3

Do not order unnecessary urgent imaging or interventions in asymptomatic patients with confirmed empty sella on MRI, as this won't change immediate management. 3, 7