Empty Sella Syndrome

Empty sella is a radiological and, in a proportion of cases, clinical entity in which the pituitary fossa (sella turcica) appears partially or completely filled with cerebrospinal fluid rather than normal pituitary tissue. Arachnoid membrane and cerebrospinal fluid herniate into the sella through an incompetent diaphragma sellae.

It is classified as primary or secondary. Primary empty sella has no identifiable prior pituitary insult and is generally an incidental finding without clinical significance. Secondary empty sella follows pituitary surgery, radiotherapy, infarction, or involution of a pre-existing pituitary tumour or lesion.

The great majority of cases, particularly primary empty sella, are incidental imaging findings without endocrine dysfunction. A minority develop clinically significant hypopituitarism, which needs hormonal assessment and, where deficiencies are identified, replacement therapy.

Pathophysiology

• Primary empty sella reflects congenital or acquired incompetence of the diaphragma sellae, the dural membrane that normally covers the pituitary fossa. Cerebrospinal fluid pulsation pressure is transmitted chronically into the sella, gradually flattening and redistributing the pituitary gland against the floor and walls of the fossa.
• The process is gradual and generally non destructive, so adequate functioning pituitary tissue is typically preserved.
• Secondary empty sella follows a prior insult to pituitary tissue: surgical resection, radiotherapy induced atrophy, infarction as in Sheehan syndrome, or spontaneous involution of a pituitary adenoma. The sella fills with cerebrospinal fluid as the previously occupying tissue or lesion volume is lost.
• The underlying process is more destructive, so secondary empty sella carries a substantially higher likelihood of clinically significant hypopituitarism.
• Risk factors for primary empty sella include female sex, obesity, and conditions associated with chronically raised intracranial pressure (including idiopathic intracranial hypertension). Sustained increased cerebrospinal fluid pressure transmission contributes to its development.

• The great majority of cases are asymptomatic from an endocrine perspective, with normal pituitary function despite the striking radiological appearance. This applies particularly to primary empty sella found incidentally on imaging for an unrelated indication (commonly headache investigation).
• Where clinically significant hypopituitarism develops, the pattern of deficiency reflects the pituitary axes affected. Growth hormone deficiency is often the earliest and most commonly identified deficit.
• In more extensive cases, gonadotropin and thyrotropin deficiency follow. Adrenocorticotropic hormone deficiency is less common but the most clinically significant, given the acute risk.
• Headache is commonly reported in primary empty sella, but the causal relationship with the radiological finding remains debated.
• Headache is frequently attributable to another cause, including coexisting idiopathic intracranial hypertension, which shares the risk factor profile.
• Rarely, cerebrospinal fluid rhinorrhoea occurs where a defect allows direct leakage from the enlarged, cerebrospinal fluid filled sella into the sphenoid sinus and then the nasal cavity. This is an uncommon but clinically important complication because of infection risk.

• Magnetic resonance imaging of the pituitary region shows cerebrospinal fluid filling the sella turcica. The residual pituitary gland is typically visible as a thin rim of tissue along the floor or walls of the fossa, which distinguishes the appearance from a truly absent or destroyed gland.
• Perform full pituitary hormonal assessment in any patient with a newly identified empty sella, particularly secondary empty sella, which carries a higher risk of hypopituitarism. The aim is to identify any clinically significant deficiency requiring treatment.
• Cover the full range of anterior pituitary axes: cortisol and, where indicated, formal dynamic testing such as a short synacthen test for adrenal reserve; thyroid function; gonadotropins together with sex hormones; growth hormone axis assessment where clinically relevant; and prolactin.
• Idiopathic intracranial hypertension shares risk factors and symptoms with empty sella, particularly in an obese woman with headache and a primary empty sella finding. Assess for it specifically, with formal visual field testing and, where indicated, lumbar puncture with opening pressure measurement.
• Idiopathic intracranial hypertension has management implications distinct from the empty sella finding itself.

• Primary empty sella with normal pituitary function on full assessment is essentially benign and incidental. It needs no treatment beyond reassurance.
• Some protocols consider periodic reassessment of pituitary function, given a small but recognised risk of gradual, progressive hormonal deficiency over subsequent years.
• Manage any identified hormonal deficiency with standard hormone replacement for the affected axis. Give adrenocorticotropic hormone deficiency particular priority and urgency, because unrecognised or inadequately treated deficiency can cause life threatening adrenal crisis.
• Secondary empty sella after pituitary surgery, radiotherapy or infarction needs the same full hormonal assessment and, where deficiencies are identified, replacement therapy.
• The underlying context and prior treatment history inform the anticipated pattern and likelihood of hormonal deficiency and guide the frequency of surveillance testing.
• Cerebrospinal fluid rhinorrhoea requires specialist ear, nose and throat and neurosurgical assessment for consideration of surgical repair, because of the risk of ascending meningeal infection if untreated.
• Manage coexisting idiopathic intracranial hypertension according to the principles for that condition, independent of the empty sella. In this context the empty sella is a radiological consequence of chronically raised intracranial pressure and needs no separate treatment.
• Ongoing endocrinology follow up, with periodic reassessment of pituitary function, is appropriate. This applies particularly to patients with secondary empty sella or any baseline hormonal deficiency, because hormonal deficiency can evolve, generally gradually, over time.