ABSTRACT

Empty sella is a radiological finding of a flattened pituitary in a sellar space filled with cerebrospinal fluid. It may be primary or secondary consequent to various processes causing injury and shrinkage of the pituitary gland (postpartum hemorrhage, pituitary surgery, irradiation, apoplexy, infection, head trauma, hypophysitis, etc.). The mechanisms involved in the pathogenesis of the so called “primary empty sella” may range from continuously or intermittently increased intracranial pressure due to idiopathic benign intracranial hypertension, obesity, arterial hypertension, or multiple pregnancies in female patients with accompanying insufficiency of the sellar diaphragm and changes in pituitary gland volume (hyperplasia during pregnancy, lactation, menopause etc.). Primary empty sella can be an incidental radiological finding in an asymptomatic patient with preserved pituitary function. In symptomatic patients with the so called “empty sella syndrome” (headache, visual disturbances and hormonal dysfunction), the radiological finding of an empty sella is important in the differential diagnosis of other sellar lesions. Hypopituitarism, partial or complete, and hyperprolactinemia are not uncommon in these patients. The treatment of hypopituitarism and hyperprolactinemia is advocated in all patients with confirmatory results. In patients with the secondary empty sella, hypopituitarism is more common and more readily recognized due to damage caused by surgery, radiation therapy, or various pathological causes. Rarely, empty sella can be associated with hormonal hypersecretion from an “invisible” micro adenoma producing prolactin, growth hormone (acromegaly) or ACTH (Cushing’s disease). A wide range of radiological findings in patients with secondary and primary empty sella coupled with clinical data (important hints from the history and data on endocrine function) are presented for further illustration of this topic. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

HISTORY

The term ‘empty sella’ was first used by Bush in 1951 (1) to describe a peculiar anatomical condition, observed in 40 of 788 human cadavers, particularly females, characterized by a sella turcica with an incomplete diaphragm sellae that forms only a small peripheral rim, with a pituitary gland not absent, but flattened in such a manner as to form a thin layer of tissue at the bottom of the sella turcica. Kaufman (2), in 1968, speculated that ‘…empty sella is a distinct anatomical and radiographic entity, function of an incompleteness of the diaphragma sellae and of the cerebrospinal fluid (CSF) pressure, normal or elevated’. The role of the normal fluctuations of CSF pressures and the effect of a superimposed prolonged increase in CSF pressure were related to the anatomic changes involving the bony wall of the empty sella.

DEFINITION, ETIOLOGY, AND PREVALENCE OF EMPTY SELLA

Empty sella is defined as herniation of subarachnoid space into the sella turcica (arachnoidocele). It is a term for the radiological finding of “empty sellar space” on magnetic resonance imaging (MRI) and computerized tomography (CT) with a flattened pituitary and elongated stalk. It can be partial if less than 50% of sellar space is filled with cerebro-spinal fluid (CSF), or complete if CSF fills more than 50% of space in the sella and gland thickness is less than 2mm (3,4).

Regarding its etiology, it can be primary if there is no pathological process in the sellar region preceding the pituitary damage or secondary if it is consequent to a specific pathological process. Primary empty sella (PES) can be an incidental finding or may arise during imaging for headache, endocrine disorders, neurological symptoms, visual disturbances, abnormal sella turcica radiograph, and other reasons.

Primary empty sella (PES) can be caused by intracranial hypertension and/or insufficiency of the sellar diaphragm in subjects with no previous history of pituitary disease. Insufficiency of the sellar diaphragm, a deflection of dura matter separating the suprasellar cistern from the pituitary fossa, allows unobstructed pulsatile movements of CSF from chiasmatic cistern causing flattening of the pituitary to the sellar floor. In extreme cases bone erosion of the sellar floor and CSF leak (rhinorrhea) may occur, increasing the risk of meningitis. Partial or complete absence of the sellar diaphragm has been demonstrated in patients with PES.

Intracranial pressure can be intermittently increased due to obesity, sleep apnea, arterial hypertension, pregnancy, and labor. Intracranial hypertension may be idiopathic or associated with other intracranial processes such as tumors, venous thrombosis, infections, or malformations. Idiopathic intracranial hypertension (IIH) or “pseudo-tumor cerebri” is a rare condition affecting 1 in 100,000 persons. It can be due to impaired CSF absorption, increased CSF secretion and/or increased capillary permeability (5). Impaired CSF dynamics and absorption have been found in up to 77% and 84% of patients with PES, respectively (6), The prevalence of PES is very high in patients with IIH ranging from 70-94% (4).

Changes in the pituitary gland volume may also be involved in the pathogenesis of empty sella syndrome including hyperplasia during pregnancy and lactation and pituitary involution after menopause accounting for the significantly higher prevalence of this condition in female patients (female to male ratio 5:1).

Factors involved in the pathogenesis of primary empty sella are shown in Figure 1.

Secondary empty sella is more common and is related to various pathological processes of the sellar region. Among many causes of pituitary tumor shrinkage occurring after medical treatment, surgery, radiotherapy, and apoplexy of a pituitary adenoma are frequent causes of secondary empty sella. Likewise, postpartum pituitary necrosis, pituitary infection, hypophysitis, and traumatic brain injury may lead to pituitary atrophy. The diagnosis of secondary empty sella is more difficult if there is no known underlying pathology involving the pituitary gland. In these cases, the sella is normal in size, and the function of the flattened pituitary gland may or may not be compromised. Such is the case in congenital causes of hypopituitarism both acquired and genetic, presenting with a hypoplastic pituitary gland and ectopic posterior lobe. Large intracranial tumors such as slow-growing meningiomas can also cause increased intracranial pressure and secondary empty sella in a significant number of patients. Pituitary MRI images of patients with secondary and primary empty sella are presented in the section dedicated to radiological appearance of an empty sella (Fig. 2-6). Associated risk factors for primary and secondary empty sella are shown in Table 1.

The reported prevalence of empty sella depends on techniques used for detection. In autopsy studies empty sella has been found in up to 5.5-12% cases (1,2), On imaging the overall incidence has been estimated at 12% (4). The prevalence of PES is very high in patients with IIH.

Figure 1.

Factors involved in pathogenesis of primary empty sella including the upper-sellar factors, incompetence or incomplete formation of the sellar diaphragm, and pituitary factors associated with the variation in the pituitary volume. Modified from Bioscientifica Ltd., Chiloiro S et al, European Journal of Endocrinology (2017) 177, R275–R285

RADIOLOGICAL APPEARANCE OF EMPTY SELLA

Most commonly an empty sella is incidentally discovered during MRI or CT imaging or during evaluation for headache, endocrine, neurological or visual disturbances. Less commonly it is observed after additional imaging for abnormal sella turcica radiographs. Chronic intracranial hypertension can lead to sellar remodeling and enlargement with thinning of the sellar floor and rarely rhinorrhea.

On typical presentation CSF filling is in continuity with overlying subarachnoid spaces and the residual pituitary gland is flattened against the sellar floor of enlarged bony sella with pituitary volume usually less than 611.21 mm³ (7). The differential diagnosis with cystic lesions and congenital pituitary abnormalities may pose a challenge. The stalk is usually thinned and located in the midline. Asymmetry is a frequent sign of the secondary empty sella. In rare cases the chiasm can herniate into the sella in cases of both primary and secondary etiology. Indirect signs of intracranial hypertension may also be present such as flattening of the posterior sclera, prominent subarachnoid spaces along the optic nerves, vertical tortuosity of the optic nerve sheath complex, and increased width of the optic nerve sheaths (8).

Sagittal and coronal T1-weighted (T1W) contrast enhanced images and coronal T2-weighted (T2W) images are strongly indicated for MR studies because they show CSF within the sella. On FLAIR sequences the intrasellar fluid completely suppresses and it presents without restriction in DWI sequences. After contrast T1W images show normal enhancement of residual pituitary gland and the stalk in PES in contrast to scaring and distortion in SES.

In patients with congenital hypopituitarism an ectopic posterior pituitary, stalk duplication or absence may be present in combination with other midline defect (agenesis of corpus callosum, supraoptic dysplasia, etc.).

Figures 2, 3, 4, 5 represent various MRI findings of patients with secondary empty sella due to postpartum hemorrhage (Sheehan’s syndrome Fig. 2), lymphocytic hypophysitis (Fig. 3), shrinkage of a macroprolactinoma after successful treatment with cabergoline (Fig.4), and congenital hypopituitarism with empty sella (Fig.5)

Figure 2.

Sagittal T1W images of two patients with empty sella and Sheehan’s syndrome

Left Panel (sagittal T1W image without contrast) and Right (sagittal T1W image after contrast enhancement) represent the MRI appearance of empty sella in two patients with Sheehan’s syndrome. Both patients presented with hyponatremic coma due to unrecognized panhypopituitarism and infection 3 and 20 years after delivery complicated by postpartum hemorrhage.

Figure 3.

Contrast enhanced coronal and sagittal T1W images of lymphocytic hypophysitis spontaneous evolution from the presentation (panel A, B), after 4 (panel C) and 10 years (panel D) of follow-up resulting in secondary empty sella.

Figure 4.

Coronal T1W images demonstrating a pituitary tumor (macroprolactinoma) shrinkage in a patient treated with the dopamine agonist cabergoline for 10 years. The patient presented with hyperprolactinemia causing galactorrhea-amenorrhea, secondary adrenal insufficiency and central hypothyroidism. Hyperprolactinemia and adrenal insufficiency completely recovered during follow up.

Figure 5.

Sagittal T1W showing small pituitary gland found at the bottom of sella, thin stalk and ectopic posterior lobe in a young adult with isolated childhood-onset growth hormone deficiency (congenital).

Figure 6.

Sagittal T1W images of pituitary stalk pressed against the dorsum sellae causing mild hyperprolactinemia in a patient with primary empty sella.

PRIMARY EMPTY SELLA (PES) AND EMPTY SELLA SYNDROME

Epidemiologically, this is associated with female sex (female to male ratio 5:1), multiple pregnancies, obesity, arterial hypertension and middle age. It may present with headaches, endocrine dysfunction, and visual disturbances due to pressure on the neighboring structures.

A typical clinical picture consists of headache and obesity. Women in the reproductive age may be affected by menstrual irregularities, galactorrhea and sterility. Man can develop gynecomastia and sexual disturbances. Primary empty sella due to the syndrome of increased intracranial pressure can also be associated with symptoms of intracranial hypertension.

TREATMENT

In patients with increased idiopathic intracranial pressure osmotic diuretics or acetazolamide (Diamox) are advocated. Weight loss may be efficient in obese and overweight patients especially if accompanied by sleep apnea. Neurosurgical techniques may be indicated for rhinorrhea and some symptomatic secondary causes of empty sella syndrome with increased intracranial pressure and acute visual disturbances. If diagnosed hypopituitarism should be replaced following the current recommendations (16) and hyperprolactinemia treated with dopamine agonists.

CONCLUSION

Primary empty sella can be heterogeneous in origin and presentations range from an asymptomatic incidental radiological finding to endocrine and neuro-ophthalmological manifestations. Female sex, multiple pregnancies, obesity, and arterial hypertension are associated risk factors as well as the syndrome of benign intracranial hypertension. Secondary empty sella is caused by various pathological processes resulting in shrinkage of the pituitary gland. Routine hormonal status assessment and regular follow-up are indicated in all patients since the prevalence of pituitary dysfunction is significant.

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