Incidentally Discovered Empty Sella: A Comprehensive Review

 

Incidentally Discovered Empty Sella: A Comprehensive Review for the Internist

Dr Neeraj Manikath , claude.ai

Abstract

Empty sella syndrome (ESS), characterized by herniation of the subarachnoid space into the sella turcica, is increasingly detected as an incidental finding on neuroimaging. With the widespread use of CT and MRI, internists must understand the clinical implications, differential diagnosis, and management of this common radiological finding. This review provides a practical approach to the incidentally discovered empty sella, emphasizing clinical pearls and diagnostic pitfalls relevant to contemporary internal medicine practice.

Introduction

The term "empty sella" describes a radiological appearance where cerebrospinal fluid (CSF) fills the sellar space, compressing the pituitary gland against the floor or walls of the sella turcica. Far from being truly "empty," the sella contains a flattened pituitary gland in most cases. The prevalence of primary empty sella ranges from 5% to 35% in autopsy series and radiological studies, with increased detection rates reflecting modern imaging capabilities rather than true disease prevalence changes.

Empty sella syndrome is classified as primary (idiopathic) or secondary (following surgery, radiation, pituitary apoplexy, or infarction). This review focuses on primary empty sella, the form most commonly encountered as an incidental finding in asymptomatic patients undergoing neuroimaging for unrelated indications.

Pathophysiology and Anatomical Considerations

The normal sella turcica is sealed superiorly by the diaphragma sellae, a dural fold with a central aperture through which the pituitary stalk passes. In primary empty sella, incompetence or congenital deficiency of the diaphragma sellae permits CSF pulsations to exert chronic pressure on the pituitary gland, gradually flattening it against the sellar floor.

Clinical Pearl: The incomplete diaphragma sellae acts as a one-way valve—CSF enters during systolic pulsations but cannot easily exit, creating a ball-valve mechanism that progressively remodels the sella over years.

Several factors contribute to diaphragmatic incompetence: increased intracranial pressure (including idiopathic intracranial hypertension), multiparity, obesity, and chronic hypertension. The association with benign intracranial hypertension is particularly important, as both conditions share common risk factors and may coexist in up to 10% of cases.

Clinical Presentation and Associations

Most patients with incidentally discovered empty sella are asymptomatic regarding pituitary function. The typical patient profile—middle-aged, multiparous, obese woman with hypertension—should prompt recognition of this clinical pattern, though men and individuals without these risk factors are also affected.

Associated Clinical Conditions

Endocrine manifestations: Contrary to historical teaching, overt hypopituitarism is uncommon in primary empty sella, occurring in fewer than 15% of cases. When present, growth hormone deficiency is most frequent, followed by gonadotropin deficiency. Complete panhypopituitarism is rare (<5% of cases).

Oyster Alert: Mild hyperprolactinemia (typically <100 ng/mL) occurs in approximately 10% of patients with empty sella due to stalk compression impairing dopamine delivery to lactotrophs. This "disconnection hyperprolactinemia" should not be mistaken for a prolactinoma, which typically produces levels exceeding 200 ng/mL.

Visual disturbances: While headache occurs in up to 80% of patients with empty sella, the causal relationship remains uncertain. Visual field defects are uncommon (<10%) but may result from herniation of the optic chiasm into an enlarged sella or coexistent idiopathic intracranial hypertension.

CSF rhinorrhea: This rare but serious complication (<1% of cases) results from bone erosion and dural defects at the sellar floor, creating a communication between the subarachnoid space and sphenoid sinus.

Diagnostic Approach

Radiological Features

MRI characteristics: T1-weighted images demonstrate signal intensity identical to CSF filling the sella, with a thin rim of pituitary tissue displaced inferiorly or posteriorly. T2-weighted sequences confirm CSF characteristics and exclude solid masses. The pituitary stalk typically maintains midline position, an important distinguishing feature from mass lesions.

Hack: Request coronal views when empty sella is suspected—they provide superior visualization of the flattened pituitary gland and demonstrate whether the gland enhances normally with contrast, confirming viable pituitary tissue.

CT findings: Less sensitive than MRI but demonstrates sellar enlargement with smooth, intact bony margins. The "double floor sign"—two distinct bony floors representing the anterior and posterior clinoid processes—may be visible.

Differential Diagnosis

The radiological differential includes several conditions that require exclusion:

Cystic sellar masses: Rathke cleft cysts, arachnoid cysts, and cystic pituitary adenomas may simulate empty sella. Unlike empty sella, these lesions demonstrate different signal characteristics from CSF on FLAIR sequences and may show rim enhancement or debris.

Post-treatment changes: Previous surgery, radiation therapy, or pituitary apoplexy can produce secondary empty sella. Clinical history is essential for distinguishing primary from secondary forms.

Oyster Alert: A partially empty sella with asymmetric pituitary tissue may harbor a microadenoma. If clinical or biochemical features suggest pituitary hypersecretion, dedicated pituitary MRI with dynamic contrast enhancement should be considered despite the empty sella appearance.

Laboratory Evaluation

The extent of hormonal evaluation in asymptomatic patients remains controversial. A pragmatic, cost-effective approach balances the low probability of significant dysfunction against the consequences of missing treatable deficiencies.

Recommended baseline assessment:

• Morning cortisol (8 AM) and ACTH
• Free thyroxine (FT4) and TSH
• Testosterone (men), estradiol and menstrual history (premenopausal women)
• Prolactin
• IGF-1 (if symptoms suggestive of growth hormone deficiency)

Clinical Pearl: A single random cortisol measurement may miss subtle ACTH deficiency. If morning cortisol is <5 μg/dL, perform ACTH stimulation testing. Values between 5-15 μg/dL warrant clinical correlation and possible dynamic testing if symptoms suggest adrenal insufficiency.

Hack: Before ordering extensive pituitary function testing, review medication lists. Opioids, glucocorticoids, and dopamine agonists profoundly affect pituitary hormones, potentially yielding misleading results.

When to Perform Formal Visual Field Testing

Perimetry is indicated when:

• Visual symptoms are present
• Sellar enlargement exceeds 12 mm in vertical diameter
• Radiological evidence suggests chiasmal herniation
• Coexistent idiopathic intracranial hypertension is suspected
• Follow-up imaging demonstrates progressive sellar changes

Management Strategies

Asymptomatic Patients with Normal Function

No specific treatment is required. Reassurance about the benign nature of the finding prevents unnecessary anxiety. The decision to perform follow-up imaging remains individualized.

Evidence-based recommendation: For truly asymptomatic patients with confirmed normal pituitary function and no visual complaints, repeat imaging is generally unnecessary. Annual clinical assessment suffices, with imaging reserved for new symptoms or signs.

Patients with Hormonal Deficiencies

Hormone replacement follows standard protocols for hypopituitarism:

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses remains the cornerstone therapy for ACTH deficiency
• Thyroid hormone: Levothyroxine replacement, with dosing guided by FT4 levels (TSH becomes unreliable with central hypothyroidism)
• Sex hormone replacement: Individualized based on age, symptoms, and contraindications
• Growth hormone: Consider in younger patients with documented deficiency and quality-of-life impairment

Oyster Alert: Always replace glucocorticoids before initiating thyroid hormone replacement in patients with multiple deficiencies. Thyroid hormone increases cortisol metabolism and may precipitate adrenal crisis in untreated ACTH deficiency.

Management of Associated Conditions

Idiopathic intracranial hypertension: Weight loss remains the most effective intervention. Acetazolamide (500-1000 mg twice daily) reduces CSF production when lifestyle modification proves insufficient. Serial ophthalmologic examinations monitor for papilledema.

Headache management: Standard migraine therapies often prove effective, though the causal relationship between empty sella and headache remains uncertain. Avoid attributing all headaches to the empty sella without considering alternative diagnoses.

CSF rhinorrhea: This complication requires prompt neurosurgical consultation. Conservative management with bed rest, head elevation, and acetazolamide may succeed in small leaks. Persistent leaks necessitate surgical repair to prevent recurrent meningitis.

Special Populations and Considerations

Pregnancy

Physiological pituitary enlargement during pregnancy typically remains well-tolerated in women with empty sella. However, the flattened gland's limited reserve may become apparent during the peripartum period or with postpartum hemorrhage (Sheehan syndrome).

Clinical Pearl: Obtain baseline pituitary function testing before conception in women with known empty sella planning pregnancy, particularly if subtle hormonal abnormalities exist.

Pediatric Patients

Empty sella in children warrants more aggressive evaluation than in adults, as growth hormone deficiency has profound implications for development. Associated congenital anomalies (optic nerve hypoplasia, midline defects) should be sought.

Postoperative Empty Sella

Secondary empty sella following transsphenoidal surgery complicates assessment for adenoma recurrence. Carefully review pre-operative imaging and operative reports. Endocrine evaluation should focus on expected deficiencies based on the original pathology and extent of resection.

Long-term Follow-up and Prognosis

Primary empty sella follows a benign course in the vast majority of patients. Progressive hormonal deterioration is uncommon, occurring in fewer than 5% of initially asymptomatic patients over 10-year follow-up periods.

Recommended surveillance:

• Clinical assessment annually, focusing on symptoms of hypopituitarism, visual changes, or rhinorrhea
• Repeat pituitary function testing only if new symptoms develop
• Repeat imaging if clinical deterioration occurs or in cases with initial concerns about mass lesions

Hack: Maintain high index of suspicion for adrenal insufficiency during acute illness in patients with known empty sella, even with previously normal function. The stress of severe illness may unmask borderline ACTH reserve. A low threshold for empiric stress-dose steroids may prove lifesaving while awaiting confirmatory testing.

Pearls for Clinical Practice

1. Not all empty sellas are created equal: Distinguish between incidental radiological findings in asymptomatic patients (requiring minimal evaluation) and empty sella discovered during evaluation of suspected pituitary disease (requiring comprehensive assessment).

2. The stalk position matters: A deviated or thickened pituitary stalk suggests infiltrative disease (sarcoidosis, Langerhans cell histiocytosis, lymphocytic hypophysitis) rather than primary empty sella.

3. Timing of imaging interpretation: Review imaging personally rather than relying solely on radiology reports. Radiologists may not recognize subtle findings relevant to endocrine assessment, such as asymmetric pituitary tissue suggesting microadenoma.

4. Document baseline function: Even in asymptomatic patients, baseline hormonal assessment provides invaluable comparison if symptoms develop years later.

5. Patient education prevents anxiety: Explicitly explain that "empty" is a misnomer and that the pituitary gland remains present and usually functional.

Conclusion

Incidentally discovered empty sella represents a common radiological finding with generally benign implications. The internist's role centers on excluding significant pituitary dysfunction, recognizing associated conditions (particularly idiopathic intracranial hypertension), and providing appropriate reassurance. A measured approach to evaluation—comprehensive enough to detect treatable deficiencies yet avoiding excessive testing in asymptomatic patients—optimizes care while controlling costs. Understanding the pathophysiology, clinical associations, and diagnostic pitfalls ensures appropriate management of this increasingly recognized condition.

Key References

1. Chiloiro S, Giampietro A, Bianchi A, et al. Primary empty sella: a comprehensive review. Eur J Endocrinol. 2017;177(6):R275-R285.

2. Auer MK, Stieg MR, Crispin A, et al. Primary empty sella syndrome and the prevalence of hormonal dysregulation: a systematic review. Dtsch Arztebl Int. 2018;115(7):99-105.

3. Guitelman M, Garcia Basavilbaso N, Vitale M, et al. Primary empty sella (PES): a review of 175 cases. Pituitary. 2013;16(2):270-274.

4. De Marinis L, Bonadonna S, Bianchi A, et al. Primary empty sella. J Clin Endocrinol Metab. 2005;90(9):5471-5477.

5. Shy N, Xie S, Cooley S, et al. Incidental primary empty sella turcica on MRI: a detailed study of referral patterns and pituitary function. J Endocr Soc. 2020;4(12):bvaa156.

6. Maira G, Anile C, Mangiola A. Primary empty sella syndrome in a series of 142 patients. J Neurosurg. 2005;103(5):831-836.

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Word Count: Approximately 2000 words

This review provides internists with a practical, evidence-based approach to managing incidentally discovered empty sella, emphasizing clinical decision-making over exhaustive discussion of rare complications. The incorporation of "pearls" (practical clinical insights), "oysters" (diagnostic pitfalls), and "hacks" (efficiency strategies) makes complex endocrinology accessible to busy clinicians managing these patients in contemporary practice.