EMPTY SELLA SYNDROME

Introduction The term empty sella was first applied to an anatomic finding at autopsy by Busch in 1951. He found that in 40 patients with no known pituitary disease, the pituitary gland was severely flattened against the floor of the sella (5.6 percent of the series); the diaphragma sellae was restricted to a thin rim of tissue around a huge infundibular foramen.

He also noted that an incomplete diaphragma might leave the pituitary gland intact but with its superior surface fully exposed and covered by arachnoid or might leave the pituitary indented and eccentrically placed within the sella. This latter condition resulted in a partially empty appearance. Busch pointed out that an empty sella was far more frequent in females than in males (34:6).

 Little clinical attention was initially paid to

Busch's interesting findings. Both radiologists and neurosurgeons usually regarded nontumoral sellar enlargement as reflecting pressure due to intrasellar arachnoidal cysts. However, Kaufman, in 1968, demonstrated that the "empty" sella was a manifestation of an enlarged intrasellar subarachnoid space. He noted that when the diaphragm a sellae was incomplete or incompetent, the subarachnoid space could expand, thus enlarging, deepening, and reshaping the sella.

 The term empty sella syndrome appeared in two

articles published in 1968. One of these papers applied the term to a patient with an enlarged sella that filled with air on pneumoencephalography; the patient had no known or demonstrable pituitary lesion. The other used the term for patients who had undergone prior surgery or radiation for proven pituitary tumors and who were later investigated for possible tumor recurrence when visual symptoms returned. An air study showed no tumor and an empty sella in each case.

 CLASSIICATION

Current usage is to call cases of sellar enlargement that are not related to a previously treated pituitary tumor primary empty sella syndrome, whereas those found following treatment of a pituitary tumor are denoted secondary empty sella syndrome. Abnormal dilation of the optic or infundibular recess as an isolated abnormality has also been reported.

 Pathogenesis An incomplete sellar diaphragm is an essential

pre-requisite for the development of the empty sella. All other factors are only predisposing to the development of intrasellar subarachnoid herniation, whether by causing increased pressure in the suprasellar subarachnoid space or by reduction in the size of the pituitary gland.

Congenital deficiency of the diaphragma sellae : Total absence of the diaphragma sellae has been reported to occur in 20.5% of normal subjects. Empty sella is also reported to occur in 5.5% of normal population.

Suprasellar promoting factors : When the diaphragma sellae is incomplete,cerebrospinal fluid pulsations act directly on the upper aspect of the pituitary gland. The suprasellar cistern pressure is accentuated when the intracranial pressure is raised. In addition, a posteriorly placed optic chiasma may also expose the upper surface of the pituitary gland and thereby increase the cerebrospinal fluid pressure on it.

 Pituitary promoting factors : Any reduction

in size of the pituitary gland favours intrasellar extension of the suprasellar subarachnoid space. Such reductions may be due to:i) Physiological involution : These occur often in women. Pregnancies bring about a large variation in the size of the pituitary gland and after delivery there is an involution. Similarly, after menopause there is a reduction in the pituitary volume. These changes explain the very clear predominance of primary empty sella in women, especially after the age of 40 years.

 A similar situation occurs in cases of

primary end-organ failure (thyroid, adrenal, gonad) wherein pituitary hyperplasia occurs due to loss of feedback control. Replacement of the deficient hormone results in feedback suppression of the pituitary tropic hormone secretion and involution of the hyperplastic pituitary gland resulting in an empty sella.

 Pathological involution : Shrinkage of

the pituitary gland may occur after postpartum pituitary necrosis (Sheehans syndrome) or pituitary infarction in patients with vascular diseases, diabetes, increased intracranial pressure, head injury, meningitis, or cavernous sinus thrombosis.

Rupture of an intrasellar or parasellar cyst: Fluid filled cysts of the sellar region are well known and may cause visual or endocrine symptoms as well as changes in the contour of the sella. Rupture of such a cyst allows intrasellar extension of the subarachnoid space. However, such rupture probably occurs only rarely.

 Clinical Presentation Although contemporary series suggest that the

presence of an empty sella is fairly common (8 to 35 percent of the population), fewer than a third of individuals with the condition ever develop symptoms. Clinical studies of the symptomatic patients with primary empty sella syndrome have revealed a variety of associated problems, and it seems likely that several etiologic factors are involved in producing an empty sella

 Despite this diversity, patients with primary

empty sella syndrome are a surprisingly homogeneous group. Over 80 percent of these patients are women, more than 75 percent are obese, and the majority become symptomatic in the decade from age 40 to 49, with over 80 percent presenting between 30 and 59 years of age. An intrasellar problem is seldom suspected when the diagnostic studies are started

 Initial complaints fall into three categories:

neurological, endocrinologic, and systemic. Headache is the most common presenting symptom, occurring in 50 to 80 percent of these patients. Other neurological complaints include memory loss, balance impairment, dizziness, seizures, and rhinorrhea.

 Papilledema, decreased visual acuity, and

visual field loss are somewhat less common (10 percent). Endocrine complaints leading to investigation include amenorrhea, galactorrhea, loss of libido, and diabetes. Systemic complaints such as obesity or hypertension lead to radiologic studies, and sellar abnormalities are revealed

 By comparison, the rare presentation of

the empty sella syndrome in children is usually marked by clinically significant endocrine abnormalities (45 to 75 percent of cases), craniofacial anomalies (30 percent), and visual complaints (as many as 35 percent)..

 Taking note of the prevalence of endocrinologic

findings and their frequent association with adverse perinatal events, Scire and colleagues showed that as many as 20 percent of children with precocious puberty have an empty sella. Smaller numbers of children with diabetes insipidus or with growth hormone deficiency will have an empty sella. Headache (13 percent) and nonspecific symptoms (4 percent) are much less common than in adults

 Radiologic Diagnosis Plain skull film or tomographic

measurements of the sella turcica should normally not exceed a length of 17 mm and a depth of 13 mm. In most patients with an empty sella, these measurements are greatly exceeded, and in a series of 20 patients the mean sellar volume was 2,77 ml..

 The primary empty sella syndrome may be

responsible for up to 25 percent of cases of enlarged sella on plain films. However, volume measurements within normal limits do not rule out an empty sella, and a sella whose measured depth exceeds its anteroposterior length also calls for further investigation

 Plain roentgenographic changes typically

include symmetrical ballooning of the sella, which still maintains a "closed" configuration. Although the floor may be considerably thinned, the clinoids are usually not attenuated. In the anteroposterior view, the sellar floor is symmetrical, in both position and bone thickness.

 Changes characteristic of pituitary tumor

including posterior displacement and demineralization of the dorsum sellae and a double contour of the sellar floor; erosion of the entire sella can also be seen. These changes may be stable or progressive

 Computed tomography (CT) and magnetic

resonance imaging (MRI) have replaced pneumoencephalography for the diagnosis of empty sella. On CT scans, an empty sella appears as a low-density abnormality in the pituitary fossa, often with erosion of the sellar floor. Following the intravenous infusion of a contrast medium. one can identify enhancement of the pituitary infundibulum and possibly the normal pituitary gland, which is usually displaced posteriorly and inferiorly. Coronal views are quite helpful..

 Before the advent of MRI, cases in which

the diagnosis was in doubt were further subjected to CT metrizamide or air cisternography via a lumbar or cervical puncture. These techniques are now rarely necessary

 The key findings that distinguish an empty sella

from a cystic mass on MRI are the isointensity of the fluid with cerebrospinal fluid (T1-weighted hypointensity and T2-weighted hyperintensity) and visualization of the infundibular stalk traversing the sellar cavity to the residual pituitary tissue. In cystic tumors or in cases of cystic degeneration of the pituitary, the infundibular stalk cannot be identified below the top of the tumor. This finding is also consistent with the diagnosis of arachnoid cyst.

 Endocrine Studies Clinical endocrine dysfunction is rare in adult

patients with the empty sella syndrome; significant abnormalities are largely restricted to secondary amenorrhea, decreased libido, and loss of pituitary reserve. However, in some series the incidence of panhypopituitarism has been as high as 10 percent. Significantly altered pituitary stimulation tests are noted in 30 to 50 percent of these patients.

 The most commonly observed abnormality

(30 percent of patients) has been deficient growth hormone (GH) secretion during stimulation tests. Abnormalities in the secretion of adrenocorticotropic hormone (ACTH) (11 percent of patients), luteinizing hormone (LH), and thyroidstimulating hormone (TSH) (15 percent) have also been reported in association with an empty sella.

 Hyperprolactinemia and intermittent increases in

prolactin (PRL) levels have both been associated with the primary empty sella, and as many as 25 percent of women with an empty sella have elevated prolactin levels. The degree of hyperprolactinemia found in empty sella syndrome is moderate (usually less than 100 ng/ml). PRL values are more elevated with prolactinomas (nearly a 1:1 association with levels greater than 200 ng/m!).

 Patients with empty sellas have a normal PRL

rise when stimulated with thyroid-releasing hormone (TRH). while patients with prolactinomas do not. Finally, the normal nocturnal peak PRL release is preserved with primary empty sella syndrome but is blunted with prolactinoma. These changes probably represent a "stalk effect" with interruption of the flow of dopamine (prolactin inhibitory factor).

 Radiologic demonstration of an empty sella does

not preclude the presence of a pituitary tumor. Functional pituitary tumors in "empty" sellas have been reported in acromegaly and Cushing's disease, and with prolactinoma. In fact, intrasellar arachnoid herniation appears to be more common with coexisting pituitary tumors than in the normal population. Intrasellar CSF extension has been observed in 14 percent of patients with acromegaly and in 17 percent of patients with prolactin-secreting tumors

 This finding suggests that infarction of

either the pituitary gland or of the tumor plays some role in the development of the empty sella in these patients. A similar mechanism has been well documented in patients with primary hypothyroidism who developed the empty sella syndrome following thyroxin-induced shrinkage of thyrotrope cell hyperplasia.

 Normal pituitary function may persist

despite extensive arachnoidal herniation with severe compression and flattening of the pituitary gland. However, cases of nontumoral hyperprolactinemia and of diabetes insipidus seen with primary empty sella syndrome suggest disruption of normal hypothalamic-pituitary pathways

 It is possible that the arachnoidal herniation

compresses the pituitary stalk at the rim of the diaphragma or upper portion of the bony sella. A similar mechanism has been proposed for certain visual problems associated with the secondary empty sella syndrome. In rare cases of empty sella syndrome following spontaneous infarction of a pituitary adenoma or in cases with Sheehan's syndrome, the precipitating process may itself be responsible for hypopituitarism.

 CSF Rhinorrhea In 1968, Ommaya and colleagues reported two cases of

CSF rhinorrhea associated with the empty sella syndrome, pointing out the relation between elevated CSF pressure and eventual rhinorrhea. They suggested that increased intracranial pressure might force open an anatomic defect not previously apparent, and thought that CSF leaks from the sella might result from persistence of the craniopharyngeal canal. Elevation of CSF pressure, combined with pulsations of the intrasellar arachnoid diverticulum, are likely causes of progressive sellar erosion and leakage

 Accurate figures on the incidence of CSF leakage

in patients with primary empty sella syndrome are not readily available. Relatively few cases of trans-sellar leakage have been reported, in view of the high incidence of empty sellas in autopsy material. Weisberg and colleagues had two patients with rhinorrhea in their group of 25 empty sellas. Others suggest that CSF rhinorrhea may affect as many as 11.8 percent of those with an empty sella. In cases of nontraumatic CSF rhinorrhea, the sella is a far less common site of leakage than the cribriform

 Establishing the correct site of CSF

rhinorrhea is of prime importance, and identification of an arachnoidal intrasellar herniation alone is not diagnostic; rather, it is necessary to demonstrate the actual site of leakage. Iohexol or metrizamide CT cisternography is currently thought to be more sensitive and specific than isotope scans

 Treatment of empty sella The primary empty sella is generally

asymptomatic and incidentally detected, it requires no specific treatment. However, when it is accompanied by endocrine dysfunction, replacement therapy of the appropriate target gland hormones would be required. Presence of CSF rhinorrhoea may require surgical correction.

 In secondary empty sella, adhesions are formed

between the diaphragma sellae and the chiasma. Retraction of these adhesions due to reduction in tumour size may pull the chiasma into the empty sella resulting in visual field defects. This needs to be corrected by chiasmopexy. Packing the sellar cavity after transphenoidal removal of the pituitary tumour can also be done to avoid herniation of the chiasma into the surgical empty sella.