BASICS
DESCRIPTION
- Normally, the pituitary gland sits in a small skull compartment at the base of the brain known as the sella turcica (Latin for "Turkish saddle"Ł).
- In empty sella syndrome (ESS), there is herniation of the suprasellar subarachnoid space into the sella turcica which acts as a mass, resulting in compression of the pituitary gland. In effect, the pituitary gland appears flattened.
- Synonym(s): intrasellar arachnoidocele
- In ESS, the empty sella is not actually "empty"Ł; it only appears to be on imaging. It actually contains the pituitary gland, pituitary stalk, arachnoid, CSF, and sometimes, the optic system and 3rd ventricle.
- Primary empty sella (PES)
- Characterized by a congenital defect of the sellar diaphragm, either a tear or complete absence of the diaphragm, allowing herniation of CSF-filled arachnoid into the sella
- The exact role that the defect plays is not currently known. Whether its presence alone is adequate to cause PES, is a predisposing factor, or is part of a larger and undiagnosed disease process has yet to be resolved.
- While there exists research claiming deficiencies of one or more pituitary hormones in PES (1), the evidence is inconsistent, raising the question of whether or not an "ESS"Ł truly exists. Associated with the following:
- Female sex
- Obesity
- Multiparity
- Intracranial hypertension in 50% of cases
- Secondary empty sella (SES)
- Results from physical destruction of the pituitary gland either from iatrogenic or noniatrogenic causes
- SES is more likely than PES to produce loss of pituitary functions, with consequent infertility and fatigue. In children:
- Is much less common and usually less likely to be benign than in adults
- Visual disturbances are seen more frequently than in adults.
- More likely to result in pituitary insufficiency than in adults
EPIDEMIOLOGY
Incidence
- ESS
- Is seen in 5.5-35% of autopsies
- Occurs at any age, in either sex. Women are generally affected more often than men with a ratio of 5:1 (PES) and increasing incidence with age.
- Most commonly found in obese, multiparous women with hypertension
- PES
- Clinically evident endocrine disturbance is rare in PES; however, some studies report abnormal pituitary function tests in as high as 30-50% of patients were studied.
- Most common reported abnormalities are as follows:
- Growth hormone deficiency
- Hyperprolactinemia
ETIOLOGY AND PATHOPHYSIOLOGY
Several proposed mechanisms á
- PES
- Incomplete formation of the sellar diaphragm overlying the pituitary. With pulsatile CSF flow and greater leakage into the sella, intrasellar pressure increases. As a result, the pituitary gland becomes compressed or appears to become compressed due to sellar expansion.
- Obesity tends to cause a hypercapnic state, which causes increased CSF pressure. This may lead to sellar expansion.
- Enlargement and subsequent involution of the pituitary gland during pregnancy has been proposed to contribute to ESS in multiparity.
- SES
- Iatrogenic causes include intracranial surgeries (especially transsphenoidal) and radiation treatment. Noniatrogenic causes include hemorrhage, infection, trauma, autoimmune conditions, or infarction of adenoma.
Genetics
ESS is not typically inherited. One known documented report of familial ESS (2). á
RISK FACTORS
- History of intracranial surgery or brain radiation
- Traumatic brain injury
- Autoimmune disease
- Infection (meningitis and encephalitis)
- History of Sheehan syndrome (postpartum hypopituitarism), more common in multiple pregnancies
- Obesity
- History of pseudotumor cerebri
COMMONLY ASSOCIATED CONDITIONS
- Benign intracranial hypertension (BIH)
- Obesity
- Pseudotumor cerebri
- Hypertension
- Diabetes mellitus
- Early menopause (nearly 10% of females with ESS)
- Sheehan syndrome
- Multiple pregnancies
DIAGNOSIS
HISTORY
- The most common complaint is headache (60-80%) with no specific clinical features (3).
- Menstrual irregularity (has been reported in up to 20% of patients with PES)
- Infertility
- CSF rhinorrhea (can increase risk of infection of meninges)
- May be associated with BIH
- Dizziness, with or without syncope
- Nonspecific visual changes, diplopia and optic neuritis, were reported in up to 16% of cases (3,4).
- Often asymptomatic
PHYSICAL EXAM
- Obesity is often the only finding.
- Papilledema (especially in cases with pseudotumor cerebri)
- Visual field deficits
- Cranial nerve disorder findings related to hormonal deficiencies or excess
- Testicular atrophy
- Gynecomastia
- Galactorrhea
- Short stature
DIFFERENTIAL DIAGNOSIS
- Intrasellar mass
- Arachnoid cyst
- Rathke cleft cyst (benign pituitary cyst)
- Epidermoid cyst
- Hypopituitarism
- Craniopharyngioma
- Pituitary macroadenoma
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Often, the "empty"Ł sella is found incidentally on CT or MRI of the brain.
- For workup, brain MRI is most effective. CT can be used but is less reliable (CT and MRI should be ordered with and without contrast).
- If sella appears empty, it is crucial for a radiologist to rule out cyst or space-occupying lesion.
- This can be done by following the pituitary stalk from the median eminence of the hypothalamus to the flattened pituitary gland at the floor of the sella turcica (usually located posteroinferiorly), so called the infundibulum sign.
- If a cyst or tumor is present, the pituitary stalk will appear to deviate away from this course.
- Basic metabolic panel looking for hyponatremia
- CBC looking for anemia
- Dual energy x-ray absorptiometry (DEXA) scan, if otherwise indicated
- Fasting morning serum
- Thyroid-stimulating hormone (TSH) and free T4
- Prolactin
- Luteinizing hormone, follicle-stimulating hormone, and testosterone( male) or estrogen (female)
- Cortisol (with cosyntropin stimulation test)
- dehydroepiandrosterone (DHEA)
- Insulin-like growth factor 1 (IGF-1)
- With concern for elevated intracranial pressure, consider the following:
- Lumbar puncture with measure of opening pressure
- Ophthalmologist referral for retinal exam
Follow-Up Tests & Special Considerations
- Antipituitary antibodies
- Follow-up CT/MRI may show improvement or progression of the empty sella in 2 to 3 years after diagnosis.
- If hypopituitarism is found, consider DEXA to evaluate bone density.
- Patients with PES should be followed up regularly with endocrinology, neurology, and ophthalmology to monitor for progression and treatment of any associated underlying medical problems.
TREATMENT
MEDICATION
- Treat only if there are resultant medical problems (no treatment, if pituitary function is normal). Each endocrine disorder is then addressed individually.
- Hyperprolactinemia
- Cabergoline, first-line treatment, but use lowest effective dose (5)[B]
- Bromocriptine
- GH deficiency (most common abnormality)
- Recombinant human GH (6)[C]
- Diabetes insipidus
- DDAVP (desmopressin acetate tablets)
- Increased intracranial pressure
- Hypothyroid
- Hypogonadism
- Adrenal insufficiency
- Hydrocortisone
- Fludrocortisone
- Osteoporosis
- Bisphosphonates
- Calcium and vitamin D
SURGERY/OTHER PROCEDURES
- Surgery is reserved for cases with persistent intracranial hypertension, severe headache, visual alterations, and CSF rhinorrhea (7)[C].
- CSF shunt for those with severe intracranial hypertension or if pressure is worsening or resistant to medical treatment. It may be required in some to prevent comorbidity (e.g., blindness) (8)[C].
- Transsphenoidal surgical approach is useful for repairing structural defects.
- Optic nerve sheath decompression is another technique to treat papilledema due to increased intracranial pressure but does not treat the underlying intracranial pressure.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- In patients with traumatic brain injury, it is important to monitor pituitary function.
- Patients found to have hypopituitarism should be monitored according to regular practice guidelines.
REFERENCES
11 De Marinis áL, Bonadonna áS, Bianchi áA, et al. Primary empty sella. J Clin Endocrinol Metab. 2005;90(9):5471-5477.22 Colliot áS, Heim áM, Vincentelli áJM, et al. Familial primary empty sella turcica. Apropos of a family with 3 cases. Ann Endocrinol (Paris). 1990; 51(1):39-42.33 Guitelman áM, Garcia Basavilbaso áN, Vitale áM, et al. Primary empty sella (PES): a review of 175 cases. Pituitary. 2012;16(2):270-274.44 Guinto áG, Mercado áM, Abdo áM, et al. Primary empty sella syndrome. Contemp Neurosurg. 2007;29(11):1-6.55 Melmed áS, Casanueva áFF, Hoffman áAR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273-288.66 Poggi áM, Monti áS, Lauri áC, et al. Primary empty sella and GH deficiency: prevalence and clinical implications. Ann Ist Super Sanita. 2012;48(1):91-96.77 Fouad áW. Review of empty sella syndrome and its surgical management. Alexandria J Med. 2011;47(2):139-147.88 Maira áG, Anile áC, Mangiola áA. Primary empty sella syndrome in a series of 142 patients. J Neurosurg. 2005;103(5):831-836.
ADDITIONAL READING
- Agrawal áNK, Jain áP, Garg áS. Primary empty sella with isolated ACTH deficiency and microprolactinoma. Gynecol Endocrinol. 2012;28(7):568-569.
- Del Monte áP, Foppiani áL, Cafferata áC, et al. Primary "empty sella"Ł in adults: endocrine findings. Endocr J. 2006;53(6):803-809.
- Komada áH, Yamamoto áM, Okubo áS, et al. A case of hypothalamic panhypopituitarism with empty sella syndrome: case report and review of the literature. Endocr J. 2009;56(4):585-589.
- Shaw áGY, Million áSK. Benign intracranial hypertension: a diagnostic dilemma. Case Rep Otolaryngol. 2012;2012:814696.
CODES
ICD10
E23.6 Other disorders of pituitary gland á
ICD9
253.8 Other disorders of the pituitary and other syndromes of diencephalohypophyseal origin á
SNOMED
- Empty sella syndrome
- pituitary dwarfism with small sella turcica (disorder)
CLINICAL PEARLS
- An incidental finding of empty sella on MRI or CT warrants a thorough history and physical exam to evaluate for signs or symptoms of hypopituitarism, with appropriate lab studies.
- Hypopituitarism frequently is not recognized in patients with ESS, especially those with advanced age.
- In most cases, treatment is not necessary unless there are resultant medical problems.