Empty Sella — High-Yield Notes

Source: The MyEndoConsult Team

1. Definition & Classification

Empty sella (arachnoidocele) = herniation of the subarachnoid space (CSF) into the sella turcica → pituitary flattened against the sellar floor, stalk elongated.

Radiologic grading

“Empty sella” is always a radiologic finding, not a clinical diagnosis. “Empty sella syndrome” = empty sella + symptoms (headache, visual changes, hormonal dysfunction).

Etiology — Primary vs Secondary

Epidemiology

• F:M = 5:1; peak middle age.
• Autopsy prevalence 5.5–12%.
• Imaging prevalence ~12% of general population (rising with MRI ubiquity).
• In idiopathic intracranial hypertension (IIH): 70–94% have empty sella.
• IIH itself: ~1/100,000 general; much higher in obese women of reproductive age.

2. Pathogenesis of Primary Empty Sella

Three converging factors:

1. Suprasellar / CSF factor — chronically or intermittently raised ICP (idiopathic, obesity, OSA, pregnancy/labor, HTN). Impaired CSF dynamics in 77% and impaired CSF absorption in 84% of PES patients.
2. Diaphragm sellae insufficiency — partial or complete absence of the dural diaphragm allows pulsatile CSF transmission into the sella.
3. Pituitary volume changes — physiological hyperplasia during pregnancy/lactation, then involution after menopause (explains the 5:1 female predominance).

In extreme cases: bone erosion of sellar floor → CSF rhinorrhea → ↑risk of meningitis.

3. Radiologic Approach

MRI is the modality of choice. Required sequences:

• Sagittal and coronal T1W pre- and post-gadolinium
• Coronal T2W (confirms CSF intensity)
• FLAIR — intrasellar fluid completely suppresses (true CSF)
• DWI — no restriction (excludes cystic neoplasms)

Typical findings

• CSF in continuity with overlying subarachnoid space.
• Flattened residual gland at sellar floor; pituitary volume often <611 mm³.
• Stalk thinned but midline (asymmetry suggests SES or other pathology).
• Sellar bony remodeling/enlargement if chronic ↑ICP.
• Optic chiasm may herniate into sella (both PES and SES).

Indirect signs of intracranial hypertension (to look for)

• Flattening of the posterior sclera
• Prominent perineural subarachnoid spaces along optic nerves
• Vertical tortuosity of optic nerve sheath
• Widened optic nerve sheath diameter
• Transverse sinus stenosis
• Tonsillar descent

Differential pitfalls

• Rathke cleft cyst — homogeneous, no CSF continuity, may have proteinaceous T1 hyperintensity.
• Arachnoid cyst — distinguishing requires demonstrating CSF communication (sometimes cisternogram).
• Cystic adenoma / craniopharyngioma — solid components, enhancement.
• Ectopic posterior pituitary (congenital) — bright spot at median eminence, hypoplastic gland.

4. Endocrine Dysfunction

Prevalence — PES

Hormones most often affected (in order)

1. Growth hormone (GHD) — most common isolated deficiency in PES. IGF-1 correlates with pituitary volume.
2. Gonadotropins (LH/FSH) — secondary hypogonadism.
3. ACTH, TSH — less common in PES, more common in SES.
4. AVP (ADH) deficiency — uncommon in PES (think SES, hypophysitis, surgery).

Hyperprolactinemia in PES

• Mechanism: stalk effect — CSF column compresses/displaces stalk → ↓dopamine delivery.
• Typically <50 ng/mL.
• Responds to dopamine agonists; gonadal status and ICP affect dynamics.

Hormonal hypersecretion (“invisible microadenoma” in an empty sella)

• Rare but recognized: Cushing’s disease, acromegaly, prolactinoma.
• An empty sella appearance increases the rate of MRI-negative Cushing’s disease — pituitary compression reduces visible adenoma volume.
• In acromegaly, PES coexistence is associated with lower preoperative PRL and lower nadir GH on OGTT.
• Functional imaging (11C-methionine PET, 68Ga-DOTATATE if SSTR-expressing) can localize occult adenomas when MRI is unhelpful.

Predictors of pituitary dysfunction in PES

• Male sex (paradoxically higher hypopit rate when men have PES)
• Complete (vs partial) empty sella on imaging
• Reduced residual pituitary volume / thickness

Hormonal evaluation indicated in ALL patients with empty sella — even when incidental. Most deficits are stable, but baseline assessment matters. Repeat testing later if new symptoms.

Suggested baseline workup

• Morning cortisol ± ACTH stimulation test
• Free T4, TSH
• LH, FSH, testosterone (men) / estradiol + menstrual history (women)
• IGF-1 (consider GH stimulation test if low or clinical concern)
• Prolactin (assess for stalk effect)
• Serum/urine osmolality + Na+ if symptoms suggest AVP deficiency

5. Clinical Features

Symptom prevalence in PES

Profile of the typical PES patient

• Middle-aged, obese, multiparous woman with chronic headache and arterial hypertension.
• May overlap with IIH — papilledema, transient visual obscurations, pulsatile tinnitus, sixth-nerve palsy.

Eye findings to look for

• Worsening visual acuity, blurred vision, diplopia
• Optic neuritis-like presentations
• Reduced retinal nerve fiber layer (RNFL) on OCT — even in asymptomatic PES — useful for monitoring
• Papilledema → mandates IIH workup (LP for opening pressure, MRV)

Vascular association

• PES is associated with cerebral small-vessel disease — periventricular white-matter hyperintensities, enlarged perivascular spaces (common pathway with chronic HTN/obesity).

6. Differential Diagnosis Considerations

7. Treatment

Address the underlying mechanism

• Idiopathic intracranial hypertension: weight loss (target 5–10%), acetazolamide (250 mg–4 g/day); topiramate as adjunct; LP-drainage / VP shunt or dural venous sinus stenting for refractory cases.
• Obesity / OSA: CPAP, weight management.
• Hypertension: standard BP control.

Endocrine management

• Replace deficits per the Endocrine Society 2016 hypopituitarism guideline:
  • Glucocorticoid first (hydrocortisone 15–20 mg/day in divided doses; stress dosing education).
  • Levothyroxine (only after cortisol replaced — risk of precipitating adrenal crisis).
  • Sex steroid replacement (testosterone, or estrogen ± progestin).
  • Growth hormone (in symptomatic adult GHD or pediatric GHD).
  • Desmopressin for AVP deficiency.
• Hyperprolactinemia: dopamine agonist (cabergoline first-line).
• Hypersecretion (rare): treat the underlying tumor — TSS, DA, SSA, etc.

Surgical / interventional indications

• CSF rhinorrhea — endoscopic skull base repair ± sellar reconstruction.
• Chiasm herniation with progressive visual loss — transsphenoidal chiasmapexy (sellar packing to elevate the chiasm). Most often seen after over-treated macroprolactinoma.
• Sellar floor erosion with risk of meningitis — osseous remodeling.

8. Pearls & Pitfalls

• An incidental empty sella is not by itself a diagnosis — but it always warrants a baseline pituitary hormone panel.
• Middle-aged, obese, multiparous, hypertensive woman with chronic headache and empty sella → think IIH; check fundi and order MRV.
• Empty sella + papilledema + obesity + female → reaches for the LP and opening pressure.
• Galactorrhea + mild ↑PRL (<50 ng/mL) + empty sella → stalk effect, not a prolactinoma. Cabergoline if symptomatic.
• CSF rhinorrhea in a patient with empty sella is an emergency — meningitis risk; refer to skull-base surgery.
• Patient with macroprolactinoma on long-term cabergoline who develops new vision changes → think chiasm herniation into empty sella; reduce dose, image, consider chiasmapexy. Do not assume tumor regrowth.
• MRI-negative Cushing’s disease with apparent empty sella → don’t stop at MRI; pursue BIPSS, and consider 11C-methionine PET.
• Acromegaly with an “empty” sella → still investigate; somatotroph adenomas can occur within an empty sella (reported in up to 14% of newly-diagnosed acromegalics in some series).
• Sheehan’s syndrome is often diagnosed years to decades after the precipitating delivery — failure to lactate, persistent amenorrhea, and fatigue are early clues. Empty sella develops over years.
• Male sex with PES is associated with higher hypopituitarism rates than female sex — counter-intuitive but consistent across cohorts.
• A “complete” empty sella carries a higher rate of hypopituitarism than partial — radiologic gradation matters.
• Replacing levothyroxine before glucocorticoids in a patient with multiple deficiencies can precipitate adrenal crisis — cortisol first, always.

9. Quick-Recall Numbers

• F:M ratio: 5:1
• Autopsy prevalence: 5.5–12%; imaging prevalence: ~12%
• PES in IIH patients: 70–94%
• Hypopituitarism in PES: ~29–52% (meta-analysis 52%)
• Panhypopit (within hypopit group): ~30–40%
• Most common deficits: GH > gonadotropins
• Hyperprolactinemia (stalk effect): ~10%; typically <50 ng/mL
• Headache in PES: ~80%; visual symptoms ~20%
• Multiple pregnancies in PES cohorts: ~58%
• Obesity in PES: ~50%; HTN ~27%
• “Complete” empty sella threshold: gland <2 mm thick or >50% CSF
• Hormonal deterioration on follow-up: ~3%
• IIH prevalence: ~1/100,000 general; ~20/100,000 in obese reproductive-age women

10. Must-Read References

1. Chiloiro S, Giampietro A, Bianchi A, Tartaglione T, Capobianco A, Anile C, De Marinis L. Primary empty sella: a comprehensive review. Eur J Endocrinol. 2017;177(6):R275–R285. doi:10.1530/EJE-17-0505 The single most useful review article on PES — pathogenesis, classification, endocrine evaluation, management framework. Essential.
2. Auer MK, Stieg MR, Crispin A, Sievers C, Stalla GK, Kopczak A. Primary empty sella syndrome and the prevalence of hormonal dysregulation: a systematic review and meta-analysis. Dtsch Arztebl Int. 2018;115(7):99–105. doi:10.3238/arztebl.2018.0099 The meta-analysis source for the 52% hypopituitarism prevalence figure and pattern of deficits.
3. Guitelman M, Basavilbaso NG, Vitale M, Chervin A, Katz D, Miragaya K, et al. Primary empty sella (PES): a review of 175 cases. Pituitary. 2013;16(2):270–274. doi:10.1007/s11102-012-0416-6 Largest single-cohort PES study; source of the obesity/HTN/multiparity epidemiology figures.
4. Carosi G, Brunetti A, Mangone A, Baldelli R, Tresoldi A, Del Sindaco G, et al. A Multicenter Cohort Study in Patients With Primary Empty Sella: Hormonal and Neuroradiological Features Over a Long Follow-Up. Front Endocrinol (Lausanne). 2022;13:925378. doi:10.3389/fendo.2022.925378 The most current long-term natural-history data — informs the “29% hormonal alteration at baseline, 3% deterioration over time” management strategy.
5. De Marinis L, Bonadonna S, Bianchi A, Maira G, Giustina A. Primary empty sella. J Clin Endocrinol Metab. 2005;90(9):5471–5477. doi:10.1210/jc.2005-0288 The foundational clinical review by the De Marinis / Giustina group; still the most-cited classical reference.
6. Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, Samuels MH. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(11):3888–3921. doi:10.1210/jc.2016-2118 The treatment standard for the hypopituitarism that follows empty sella diagnoses.
7. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159–1165. doi:10.1212/WNL.0b013e3182a55f17 The modified Dandy criteria for IIH — essential for differentiating the IIH-driven empty sella cases.
8. Himes BT, Bhargav AG, Brown DA, Kaufmann TJ, Bancos I, Van Gompel JJ. Does pituitary compression/empty sella syndrome contribute to MRI-negative Cushing’s disease? A single-institution experience. Neurosurg Focus. 2020;48(6):E3. doi:10.3171/2020.3.FOCUS2084 Important link between empty sella and MRI-occult Cushing’s disease — relevant when a hypercortisolemic patient has a normal-looking MRI.
9. Barzaghi LR, Donofrio CA, Panni P, Losa M, Mortini P. Treatment of empty sella associated with visual impairment: a systematic review of chiasmapexy techniques. Pituitary. 2018;21(1):98–106. doi:10.1007/s11102-017-0842-6 The reference for chiasmapexy indications and techniques — useful when a treated macroprolactinoma causes secondary chiasm herniation.
10. Maira G, Anile C, Mangiola A. Primary empty sella syndrome in a series of 142 patients. J Neurosurg. 2005;103(5):831–836. doi:10.3171/jns.2005.103.5.0831 Classic surgical neurology series describing the CSF-dynamics rationale for PES and the spectrum of presentations.