empty sella syndrome part 1

A University of the East-Ramon Magsaysay Memorial Medical Center
Graduate School- Nursing


Aquino, Felix SP
Sarmiento, Noel
______________________________________________________________________

In the earlier days, the radiographic appearance of an enlarged sella turcica was frequently equated with the presence of an intra or perisellar neoplasm. It was found, however, in some of these patients on pneumoencephalography, that the enlarged sella was not occupied by a tumour mass, but a significant amount of air was reaching the sella indicating that the subarachnoid space was extending well below the clinoid processes. To describe this finding, several different terms were used such as intrasellar arachnoid diverticulum, intrasellar cysts, deficient sellar diaphragm, intrasellar cistern. (Agarwal, 2001)

Busch, who reports the presence of empty sella in 5% of normal subjects on autopsy studies, coined the term “empty sella” to describe this condition (Agarwal, 2001) . 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). (Elias, 2005)

However, Kaufman, 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. (Elias, 2005)

However, the term empty sella in fact, is a misnomer as the sella is not completely empty, but the pituitary is always present both anatomically and functionally, though often it is displaced downwards and compressed by CSF pressure. An empty sella thus is usually an incidental anatomic finding and occasionally it results in abnormal pituitary function. Regardless of the size, the sella is completely or partially filled with CSF.



The empty sella turcica is defined as an intrasellar herniation of the suprasellar subarachnoid space with compression and some degree of flattening of the pituitary gland producing in many cases a remodelling of sella which results from a combination of incomplete diaphragm sellae and an increased CSF fluid pressure (Agarwal, 2001).

People with empty sella syndrome have a defect in the tissue barrier that normally keeps the cerebrospinal fluid around the brain separate from the sella turcica. As a result, cerebrospinal fluid puts increased pressure on the pituitary gland and the walls of the sella turcica. The sella turcica may enlarge, and the pituitary gland may shrink.

There are two types of ESS. 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.

Primary empty sella (PES) has several etiopathogenetic hypotheses that have been proposed, including a congenital incomplete formation of the sellar diaphragm and supra sellar factors such as stable or intermittent increase in intracranial pressure as well as volumetric changes in the pituitary.

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 diaphragm sellae. Total absence of the diaphragm 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. (Agarwal, 2001).

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. (Agarwal, 2001).

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:

 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. 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’. (Agarwal, 2001).

 Pathological involution : Shrinkage of the pituitary gland may occur after post-partum pituitary necrosis (Sheehan’s syndrome) or pituitary infarction in patients with vascular diseases, diabetes, increased intracranial pressure, head injury, meningitis, or cavernous sinus thrombosis. (Agarwal, 2001).

Rupture of an intrasellar or parasellar cyst: Fluid filled cysts of the sellar region are wellknown 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. (Agarwal, 2001).

Secondary empty sella may be caused either by pituitary adenomas undergoing spontaneous necrosis (ischemia or hemorrhage) or by infective, autoimmune, and traumatic causes or by radiotherapy, drugs, and surgery. (Marinis, 2005)

• Sellar or parasellar surgery
• Radiation therapy for an intrasellar expansion
• Bromocriptine therapy for a pituitary adenoma


Sociodemographic factors

Empty sella syndrome is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Empty sella syndrome, or a subtype of Empty sella syndrome, affects less than 200,000 people in the US population. (WrongDiagnosis 2007).

According to Balaganapathy (2009) a 5:1 female male predominance exists in the incidence of diaphragmatic defects.In addition, the study conducted by Marinis (2005) showed that 171 female and 42 male patients affected by PES (over 4:1 sex ratio). According to the study of Marinis (2005) , the peak incidence of ESS occurred between the ages of 30 and 40, being somewhat earlier in women than in men, perhaps because of the greater frequency of pituitary examination in women with oligomenorrhea.Of the female patients with PES, only 19 did not undergo at least one pregnancy.. In detail, about 57% of these women were multiparous (53, 23, and nine patients had, respectively, two, three, and four pregnancies). On the other hand, pregnancy could promote the onset of PES (21, 22). In fact, the pituitary volume could double during pregnancy, particularly in the case of multiple pregnancies This may contribute to cause the herniation of subarachnoid space in case of hypoplastic diaphragma sellae and/or cerebrospinal fluid (CSF) hypertension, even if moderate and temporary. (Marinis, 2005)
In the study conducted by Marinis (2005), most of the patients (155 of 213, 73%) were overweight [body mass index (BMI) _ 25 kg/m2]. Some of the patients were significantly obese (BMI _ 30 kg/m2) (25 females, i.e. 15% of total female patients, ; five males, i.e. 12% of total male patients, to BMI is reported. PES has also been reported to be associated with obesity. In fact, it is believed that morbid obesity may induce hypercapnia which can be the cause of chronic CSF pressure elevation and in turn may lead, in subjects with hypoplasic diaphragma sellae, to the intrasellar herniation of the suprasellar subarachnoid space (3, 18). The data suggest that morbid obesity may play a marginal role, if any, in the pathogenesis of empty sella because the prevalence of this phenotype does not appear to be clearly elevated in our PES population with respect to the general population.

SIGNS AND SYMPTOMS

Headache is the most common symptom. Pulsations of CSF against the dura of the sella could be responsible. (Balaganapathy, 2009). Visual alterations may be due to traction on the chiasm or involvement of chiasmal blood vessels. Incidence is about 20% in primary empty sella syndrome. In secondary empty sella syndrome the incidence is much higher because of the underlying sellar pathology. Clinically the patients complain about clouding of vision, color vision defects, photophobia, and various visual field defects (bitemporal hemi-, or quadrantanopia, generalized filed constriction, quadrine constriction, central scotoma, homonymous hemiachromatopsia mimicking the lesion in patients with a suprasellar pituitary tumour. On fundoscopy changes to the retina and papilledema can be observed. The symptoms sometimes resemble a low pressure glaucoma thus necessitating detailed ophthalmologic examination with particular attention being paid to intraocular pressure and optic disc appearance. (Balaganapathy, 2009)

Endocrinological disturbances: There is general agreement in the literature that anterior pituitary dysfunction necessitating hormonal replacement therapy is rare in primary empty sella syndrome. However, subtle dynamic endocrine testing is able to reveal some degree of hypothalamic-pituitary dysfunction in up to 80% of the patients assessed. (Balaganapathy, 2009)

Spontaneous cerebrospinal fluid rhinorrhoea: The etiology is poorly understood. Considerable proportions of patients with cerebrospinal fluid rhinorrhoea harbour a pituitary tumour or present radiologically with an empty sella of normal size or an empty sella syndrome. Incidence of cerebrospinalfluid rhinorrhoes associated with an empty sella is reported up to 15%. (Balaganapathy, 2009)

Most persons with primary empty sella are asymptomatic and the detection of this abnormality may be incidental. Typically primary empty sella syndrome occurs in obese, multiparous women. These patients sometimes may have headache and hypertension. The headache has no characteristic pattern or localisation and hence may lead to an x-ray examination which leads to the finding of this incidental abnormality. Infrequently, visual abnormalities have been reported in the form of diminished visual acuity, peripheral field constriction, bitemporal hemianopia, or quadrantinopia. Endocrine abnormalities are not a common occurrence. Hyper-prolactinaemia occurs occasionally, possibly due to stalk stretching or coincidental micro-prolactinomas. Growth hormone secretory reserve is often abnormal in these patients, probably as a result of obesity. Occasionally, thyrotropin and gonadotropin deficiency is also noted. Rarely, empty sella is associated with hormone excess possibly due to coexisting micro-adenoma within the compressed gland7. Spontaneous CSF rhinorrhoea and pseudotumour cerebri are two syndromes occasionally associated with an empty sella. (Reddy, 2005)

Secondary empty sella

The predominant clinical finding in these patients is visual abnormality, occurring due to arachnoidal adhesions and traction on the optic apparatus. They may have initial improvement in visual symptoms with surgery followed by the recurrence of symptoms due to the development of empty sella. Individuals with secondary ESS due to destruction of the pituitary gland have symptoms that reflect the loss of pituitary functions, such as the ceasing of menstrual periods, infertility, fatigue, and intolerance to stress and infection. (NINDS, 2008).


Complications

In view of the increased intracranial pressure and traction over the optic chiasma caused by the post-surgical adhesions, visual field defects are known to occur and often require treatment. (Agarwal, 2001). Moreover, Cerebrospinal fluid rhinorrhoea can occur presenting as a non-traumatic and persistent nasal discharge. This can also increase the chance of spread of infection to the meninges. (Agarwal, 2001). Also, Long standing increase in the intrasellar pressure can also lead to pituitary dysfunction, which, if present needs to be corrected with appropriate hormone replacement therapy. (Agarwal, 2001)

According to Elias (2005), he mentioned that 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).


References:

Agarwal J. et al.. (2001). Empty Sella Syndrome. Journal, Indian Academy of Clinical Medicine Vol. 2, No. 3

Balaganapathy, M. (2009) Empty sella syndrome. Retrieved on February 14, 2010 at http://www.thamburaj.com/empty_sella.htm

Bensing, S., Rorsman, F., Crock, P., Sanjeevi, C., Ericson, K., Kampe, O., Brismar, K., Hulting AL. ( 2004). No evidence for autoimmunity as a major cause of the empty sella syndrome. Exp Clin Endocrinol Diabetes 112:231–235

Elias, M.(2005). Empty sella syndrome. Retrieved on February 14, 2010 at http://pituitaryadenomas.com/emptysella.htm

Gasperi M, Aimaretti G, Cecconi E, Colao A, Di Somma C, Cannavo` S, Baffoni C, Cosottini M, Curto` L, Trimarchi F, Lombardi G, Grasso L, Ghigo E, Martino E 2002 Impairment of GH secretion in adults with primary empty sella. J Endocrinol Invest 25:329–333

Marinis et al, Extensive Clinical Experience: Primary Empty SellaJ Clin Endocrinol Metab, September 2005, 90(9):5471–5477

Melmed S, Kleinberg D. (2008). Anterior pituitary. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams Textbook of Endocrinology. Philadelphia, PA: Saunders Elsevier;

National Institute of neurological disorders and stroke. (2008). Empty Sella Syndrome Retrieved on February 14, 2010 at http://www.ninds.nih.gov /disorders/emptysella /emptysella.htm

WrongDiagnosis.( 2007).Empty Sella Syndrome Retrieved on February 14, 2010 http://www.wrongdiagnosis.com/medical/empty_sella_syndrome.htm

Reddy et al (2005). Primary empty sella syndrome, Retrieved on February 15, 2010 at http://thejns.org/doi/abs