What is empty sella syndrome?

What is Empty Sella Syndrome?

Empty sella syndrome (ESS) is a clinical condition where cerebrospinal fluid herniates into the sella turcica, compressing and flattening the pituitary gland, resulting in endocrine, ophthalmological, and/or neurological symptoms—though the radiographic finding of empty sella alone without symptoms is simply called "empty sella" and is often an incidental finding. 1, 2

Definition and Classification

Empty sella is fundamentally a radiographic finding characterized by CSF filling the sella turcica with associated compression of the pituitary gland. 1 The condition is classified into two distinct forms:

• Primary empty sella (PES): Occurs without any history of pituitary pathology, surgery, radiation, or pharmacologic treatment of the sellar region, and is considered idiopathic. 2
• Secondary empty sella: Develops after treatment of pituitary tumors (neurosurgery, drugs, or radiotherapy), spontaneous necrosis of adenomas, pituitary infections, autoimmune diseases, or brain trauma. 2

Epidemiology and Clinical Significance

• The incidence of empty sella on neuroimaging is approximately 12%, but can reach 35% in clinical practice. 3
• Most cases represent only a radiological finding without clinical implications—the majority of patients never become symptomatic and maintain good quality of life. 1
• However, approximately 30% of patients with empty sella demonstrate some degree of hypopituitarism upon testing, though most remain asymptomatic. 4, 5
• Endocrine pituitary disorders, defined as at least one hormone deficit, are reported in 19-40% of patients. 3

Pathophysiology

The underlying mechanisms vary:

• Congenital deficiency: A deficient or missing sellar diaphragm allows CSF pulsations to herniate into the sella, gradually compressing the pituitary gland. 6
• Increased intracranial pressure: Can induce sellar enlargement and emptiness, particularly in idiopathic intracranial hypertension (IIH), where partially empty sella is a typical neuroimaging feature. 4
• Spontaneous tumor necrosis: Evidence suggests that many enlarged empty sellae result from spontaneous necrosis of previous pituitary adenomas, explaining the frequent presence of pituitary insufficiency, hypersecretion, and visual field defects. 6

Clinical Manifestations

When symptoms occur (constituting true empty sella syndrome), they include:

• Endocrine dysfunction: Thyroid-stimulating hormone, T3, and T4 deficiencies occur in up to 48% of cases; elevated prolactin levels in approximately 28% of cases. 5
• Visual symptoms: Dysopsia, visual field defects, and declining visual acuity may occur from optic chiasm compression. 7, 6
• Neurological symptoms: Headache with features of increased intracranial pressure, though headache alone should not be attributed directly to empty sella as it is usually an incidental finding unrelated to headache symptoms. 4, 5
• CSF rhinorrhea: Rarely, spontaneous cerebrospinal fluid leakage can occur. 4, 6

Diagnostic Approach

• MRI is the gold standard: High-resolution pituitary protocols confirm the diagnosis even without IV contrast, offering superior tissue characterization compared to CT, which is fundamentally inadequate for evaluating sellar pathology. 5, 8
• Mandatory hormonal screening: All patients should undergo comprehensive hormonal screening regardless of symptoms, including thyroid function, adrenal axis, gonadal axis, prolactin, and growth hormone axis, as affected-axis rates often exceed 10% and may reach 50%. 4
• Ophthalmological evaluation: Formal assessment for papilledema is recommended, particularly if visual symptoms are present or concerns about increased intracranial pressure exist. 1, 4

Critical Clinical Pitfalls

• Do not overlook IIH: In patients with headache and partially empty sella, idiopathic intracranial hypertension represents a distinct clinical entity requiring specific management, primarily weight loss. 4
• Do not miss hormonal deficiencies: Despite the asymptomatic nature of many cases, failure to perform appropriate screening can miss rare but important hormonal deficiencies. 5
• Do not attribute headache to empty sella: This is usually an incidental finding unrelated to headache symptoms; consider more common headache etiologies. 5