The empty sella

The empty sella

478 Journal of Manipulative and Physiological Therapeutics Volume 22 • Number 7 • September 1999 0161-4754/99/$8.00 + 0 76/1/100395 © 1999 JMPT The ...

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Journal of Manipulative and Physiological Therapeutics Volume 22 • Number 7 • September 1999 0161-4754/99/$8.00 + 0 76/1/100395 © 1999 JMPT

The Empty Sella William W. Atherton, DC,a and Norman W. Kettner, DCb

ABSTRACT Objective: To discuss the diagnostic imaging findings of an empty sella in a chiropractic patient with emphasis on magnetic resonance imaging (MRI) of normal and abnormal pituitary appearances. Clinical Features: A 44-year-old woman started having headache, dizziness, nausea, vomiting, and diarrhea after an argument with her boyfriend. She had been treated for acute torticollis for three weeks when the new symptoms began. Consultation with an internist led to an MRI examination of the cerebellopontine angles to exclude an acoustic neuroma. The MRI demonstrated an enlarged empty sella. There was no history of pituitary tumor or other sellar disease.

INTRODUCTION The term “empty sella” (ES) was introduced by Sheehan and Summers in 1949 while describing pituitary necrosis in postpartum women.1 Two years later, Busch performed a large study and applied the term to describe nonvisualization of the pituitary gland while viewing the sella turcica at an autopsy or surgery.2 Of 788 cadavers devoid of known pituitary disease, he found 40 (5%) with an absent diaphragma sellae and herniation of the arachnoid into the sella, with no visible pituitary gland. Subsequent autopsy studies have shown similar results in approximately 20% of normal persons.1 An empty sella is defined as a sella that is at least partially filled with cerebrospinal fluid (CSF). It can be classified as either primary (idiopathic) or secondary and can result from previous surgery, radiation therapy, or other medical treatment of the pituitary gland.3 In addition, an ES can be either enlarged or normal in size. An unenlarged ES is a frequent autopsy finding and can be regarded as a normal variant. However, an enlarged ES is often associated with pituitary disease and should prompt further diagnostic work.3 Various symptoms have been associated with an ES, including pituitary insufficiency or hypersecretion, headache,

a Resident in Diagnosis Imaging, Logan College of Chiropractic, Chesterfield, Mo. b Chair, Department of Radiology, Logan College of Chiropractic, Chesterfield, Mo. Submit reprint requests to: William W. Atherton, DC, Resident in Diagnostic Imaging, Logan College of Chiropractic, 1851 Schoettler Road, P.O. Box 1065, Chesterfield, MO 63006-1065. Paper submitted November 25, 1998.

Intervention and Outcome: There was complete remission of the symptoms after 1 additional dizzy spell that occurred 3 days after the initial symptom. No intervention was performed, but the stress levels in her life had been reduced. Conclusion: An enlarged empty sella can be present without symptoms and can represent an incidental finding on radiography and MRI. However, an enlarged sella seen on lateral cervical spine radiographs should prompt further evaluation to rule out pituitary disease. The normal pituitary has a varied appearance and signal intensity on MRI depending on the patient’s age and pregnancy status. (J Manipulative Physiol Ther 1999;22:478-82) Key Indexing Terms: Pituitary Gland; Sella Turcica; Magnetic Resonance Imaging

obesity, visual disturbances, benign intracranial hypertension (pseudotumor cerebri), nontraumatic CSF rhinorrhea, and hydrocephalus. The various combinations of these symptoms make up ES syndrome.3 Plain film radiography and multidirectional conventional tomography were the first imaging modalities used to diagnose sellar disease. Later, in the early 1970s, pneumoencephalography was perfected, showing air extending below the diaphragmatic line. Subsequently the advent of computed tomography (CT) allowed direct visualization of the pituitary gland and the surrounding bony anatomy, eliminating the use of pneumoencephalography and conventional tomography.4 Today, magnetic resonance imaging (MRI) has replaced CT as the optimal modality in the evaluation of the sellar region.1 We present a case of asymptomatic primary enlarged ES with emphasis on the MRI findings in the normal pituitary gland.

CASE REPORT A 44-year-old woman had been treated for acute torticollis for 3 weeks when she began having dizzy spells, nausea, vomiting, and diarrhea. When questioned about the dizziness, she reported occasional feelings of being “pulled” but at other times having generalized dizziness. Episodes lasted from 2 to 10 minutes. She also reported that 2 days earlier she had tinnitus that alternated between the right and left ears with a headache that started at the base of the skull and extended across the top of her head. The dizziness began 3 days earlier after an argument with her boyfriend. She was a passenger in a vehicle when she was overtaken by intense dizziness and nausea. When the vehicle stopped, she vomited. The patient denied symptoms, stating only that she wished to close her

Journal of Manipulative and Physiological Therapeutics Volume 22 • Number 7 • September 1999 The Empty Sella • Atherton and Kettner






Fig 1. A, Midsagittal T1-weighted (500/20) MRI demonstrates enlargement of the sella with extension of the infundibulum into the base of the fossa (arrow). The superior portion of the fossa is filled with CSF, and the adenohypophysis is isointense to the pons. Note the normal high signal within the neurohypophysis (arrowhead). B, Contrast-enhanced image shows uniform uptake of gadolinium in the pituitary gland. This is a normal finding due to the lack of a blood-brain barrier. C, The postcontrast axial image shows the infundibulum (arrow) surrounded by the CSF-filled subarachnoid space. Note the close proximity of the carotid siphons (arrowheads). D, Coronal T1-weighted (580/20) MRI shows the herniation of the chiasmatic cistern into the sella (arrow). The infundibulum extends from the hypothalamus into the fossa, where it is connected to the posterior pituitary. Below the sella, the sphenoid sinus is not completely aerated, a normal variant.

eyes until the symptoms subsided. She described the episode as severe and later had two similar occurrences of lesser intensity at home. The patient had been diagnosed with irritable bowel syndrome 5 years earlier and reported occasional watery stools. However, the nausea and vomiting occurred only after the dizzy spells. Vital signs were normal, and the orthopedic examination revealed only restricted right lateral flexion and rotation from hypertonic contralateral trapezius and scalenes. Neurologic, otologic, and ophthalmologic examinations were unremarkable.

The patient consulted an internist for the dizzy spells after being unable to reach her chiropractor. A brain MRI was ordered to rule out an acoustic neuroma. Plain radiographs had not been obtained earlier but were performed at a later date to evaluate the bony sella.

Imaging Findings MRI was performed via 3.0 mm midcoronal, axial, and sagittal slices through the cerebellopontine angles, with and without contrast. T1, T2, and fluid attenuation inversion


Journal of Manipulative and Physiological Therapeutics Volume 22 • Number 7 • September 1999 The Empty Sella • Atherton and Kettner

skull radiographs are not commonly performed in chiropractic clinics; however, cervical series are, and a well-positioned lateral cervical view should show the sella turcica. It is important to screen the sellar region on these views for signs of enlargement and/or erosion.


Fig 2. Lateral spot radiograph of the sella turcica demonstrates marked enlargement of the fossa, measuring 18 mm long and 20 mm deep (arrowheads). This remodeling is most likely the result of an enlarging pituitary adenoma. recovery (FLAIR) 5.0 mm slices were taken from the foramen magnum to the vertex. The pituitary gland and sella were well visualized. The sella turcica was enlarged, and the pituitary occupied only 50% of the fossa. The anterior and posterior hypophyses were distinct, with a concave superior margin. There was normal high-signal intensity from the neurohypophysis, while the adenohypophysis was isointense to the pons. The infundibulum extended into the base of the fossa, and the material within the superior portion of the fossa followed the signal intensity of CSF, consistent with herniation of the arachnoid into the fossa. There was no evidence of a mass or abnormal enhancement pattern within the gland (Fig 1). Plain radiographs of the sella turcica, including bilateral lateral spots and a Towne’s projection, demonstrated a markedly enlarged sella (Fig 2) that measured 18 mm long, 20 mm deep, and 12 mm wide. In the formula V = 1⁄2(L × D × W), the volume (V) was calculated to be 2.160 cm3. A sella is considered to be enlarged when its volume exceeds 1.200 cm3 as calculated from plain films.3,5 The maximum sellar dimensions on a single lateral view of the skull are 16 mm long (anteroposterior) and 12 mm deep (superoinferior).6 Lateral

The pituitary gland is derived from both the ectoderm in the roof of the pharynx (anterior and intermediate lobes) and as an outgrowth from the floor of the hypothalamus (posterior lobe). It is situated within the sella turcica and surrounded by dura mater. The dura is reflected upon itself above the pituitary, forming the sellar diaphragm or diaphragma sellae. The dura separates the gland from the osseous sella anteriorly, inferiorly, and posteriorly. It also separates the gland from the cavernous sinuses laterally. The infundibulum pierces the sellar diaphragm, connecting the posterior lobe and hypothalamus. Approximately 20% of normal subjects have an absent or rudimentary diaphragma sellae in which the pituitary is freely exposed.3,7 The hormones secreted by the neurohypophysis are produced in hypothalamic nuclei and transported down the axon to the nerve endings in the posterior lobe. These hormones, antidiuretic hormone (ADH) and oxytocin, are carried along the axon by proteins called neurophysins.8 The secretory cells that make up the anterior lobe produce the hormones released there. The pars intermedia is almost absent in human beings but does secrete a hormone in lower animals that acts on pigment cells.7,8 The diagnosis of primary ES is possible only when there is no history of medical intervention9; this was the case with this patient. Although the patient had headache, nausea, and vomiting, these symptoms likely were not related to the empty sella. The symptoms typically ascribed to ES syndrome include headache, obesity, hypertension, endocrinological disorders, visual disturbances, and CSF rhinorrhea.3,9 Headache is a frequent complaint in 60% to 80% of patients.1 Hyperprolactinemia and growth hormone insufficiency are the most common endocrine disturbances seen in primary ES.3,10 Only the headache in this patient matches reported symptoms of ES syndrome. However, ES syndrome headache usually occurs daily and is anteriorly localized.9 This patient’s description of her headache matched that of a tension headache, starting as it did at the base of the skull and extending across the top of the head. Laboratory analyses to evaluate serum hormone levels were not clinically indicated in this case. The nausea and vomiting were likely nonorganic or gastrointestinal in origin and unrelated to the enlarged ES. In follow-up, these symptoms have resolved as stress levels decreased in the patient’s life. She reported 1 additional dizzy spell 3 days after the initial evaluation and has since been in remission. Her irritable bowel symptoms stabilized after 1 week and rarely returned in response to unusually high psychological stress. For these reasons, the patient’s chief symptoms were probably not the result of ES syndrome. In a review paper by Bjerre,3 an ES of normal size is regarded as a normal variant, whereas an enlarged ES is

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associated with pituitary disease or other clinical disorders. He also points out that even an enlarged ES can be an incidental finding, as it was in this case. Many theories explain enlargement of the sella. Bjerre discounts the theory that increased intracranial pressure is a major cause of chiasmatic cistern herniation into the sella because most patients with an enlarged ES have normal intracranial pressure. In addition, patients with hydrocephalus rarely have an enlarged ES. He also rejects the theory that previous pituitary hypertrophy is involved because an increase in sellar volume has not been observed in either peripheral gland insufficiency (ie, primary hypothyroidism) or during pregnancy. The theory receiving the most support is that an enlarged ES reflects a stage in the spontaneous course of some pituitary adenomas.1 The bony enlargement is a result of the growing adenoma, whereas spontaneous necrosis may allow herniation of the subarachnoid space after absorption of the necrotic material. This theory explains the enlargement of the sella, the presence of pituitary hypersecretions, chiasmal lesions, spontaneous CSF rhinorrhea, and possibly even pseudotumor cerebri. Approximately 10% of patients with pseudotumor cerebri have an enlarged ES,3 and 70% have an ES.11 However, no clear pathogenic mechanism between pseudotumor cerebri and an ES has been elucidated. Necrosis of a pituitary adenoma also explains the lack of further sellar enlargement once an enlarged ES has been diagnosed.3 The onset of pituitary necrosis with hemorrhage can have no symptoms or variable symptoms such as classic pituitary apoplexy or a minor attack.1 This patient had neither a remote history of apoplexy, a condition signaled by the sudden onset of headache, nausea, vomiting, vertigo, and even loss of consciousness, nor had she had a specific, minor attack consisting of some combination of headache, nausea, vomiting, and vertigo. Wakai et al12 investigated 560 consecutive cases of pituitary adenomas and found that 93 (16.6%) were hemorrhagic. The hemorrhage manifested as a major attack (classic apoplexy) in 38 (6.8%) patients, as a minor attack in 13 (2.3%), and asymptomatically in 42 (7.5%). This case report fits in the latter category. The confirmatory investigation of choice for an ES is MRI,13 which has become an important tool for assessing the pituitary because of its superior physiologic and anatomic characterization of soft tissues.10 Although CT with metrizamide cisternography can show CSF extending into the fossa, MRI more clearly shows the CSF within the fossa, a central stalk, and deformity of the gland.13 In addition, MRI does not use ionizing radiation, produces higher resolution in multiple planes, and demonstrates more clearly the relationship of the optic chiasm and cavernous sinuses.1 The signal intensity, size, and shape of the normal pituitary gland are variable with age and pregnancy.14 The morphology was found to be bulbous for the first 2 months of life and to assume a flatter upper surface (as with adults) after that age.15 The pituitary gland and stalk undergo slight linear growth throughout childhood until the advent of puberty, when they become much larger than any other time in life.14 It may even be convex at its superior surface during


adolescence, especially in girls. After the onset of adulthood, gland size stabilizes and remains constant until the sixth decade, beyond which a gradual involution occurs in both sexes.14 Pregnancy also alters the morphology of the pituitary gland. During pregnancy the mother’s gland enlarges, reaching its maximum size during the first week after birth. It rapidly returns to normal size after this first week whether the mother breastfeeds or not.14 The anterior lobe may exhibit high signal intensity on T1weighted (T1w) images in several normal states.16 A high T1w signal may be seen normally in fetuses, neonates, and pregnant or postpartum women. Wolpert et al17 showed that the pituitary gland in the infant has a shorter T1 (higher signal intensity) than does the gland in the older child. Since the posterior lobe also has high-signal intensity on T1w images, the entire pituitary gland is hyperintense. This finding is quite different from the well-established observation of high-signal intensity in only the posterior gland in adults, while the anterior lobe is isointense to the pons.15 The MRI signal intensity of the posterior lobe remained hyperintense to the pons for all age groups in a study of 76 infants and children ranging in age from 3 days to 4 years.15 This study also documented the gradual diminishing of the anterior lobe signal intensity, which becomes isointense with the pons (as seen in adults) by 2 months of age. Wolpert et al17 have suggested that the mechanism of T1 shortening in the neonate (<2 months of age) may be related to increased amounts of endoplasmic reticulum and protein synthetic activity. Pregnant and postpartum women also have a normal high-signal intensity in the anterior pituitary on T1w images.18 Miki et al18 point out that the anterior lobes of pregnant and postpartum women share histological similarities with infants in that they both have an increase in prolactin cells. Consequently, it is believed that the mechanism of T1 shortening of the anterior pituitary is the same as that in infancy. It was concluded that a hyperintense anterior pituitary lobe is a normal finding in pregnancy. This information is important when ruling out pituitary disease such as hemorrhage, Sheehan syndrome, or lymphocytic adenohypophysitis in pregnant patients.18 The signal intensity of the posterior pituitary is normally high on T1w images. Originally, this bright signal within the posterior lobe was thought to result from a fat pad around the sella. This theory proved incorrect after evidence was acquired from T2w, chemical shift, and magnetization transfer experiments.14,19 These studies show that high-signal intensity arises from water protons instead of lipid protons and has been attributed to storage of the neurophysinpeptide complex in the posterior lobe.10,14 In a study characterizing the changes of the pituitary gland, this expected posterior lobe bright signal was not detected in 29% of 59 elderly (>70 years of age) patients.10 It was hypothesized that excessive release of ADH from the posterior lobe that occurs as a result of persistently elevated plasma osmolality in the elderly may lead to depletion of the neurosecretory granules in the posterior lobe and manifest as a disappearance of bright signal on T1w images. It is also possible that


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these changes occur physiologically with aging. The posterior lobe bright signal is absent in patients with diabetes insipidus.20 This finding corroborates the theory that an excessive release of ADH depletes the neurosecretory granules and causes decreased signal intensity within the posterior lobe. Since the pituitary gland lacks a blood-brain barrier, rapid and uniform enhancement is seen after the administration of gadolinium.18 The degree of enhancement is brighter than the brain but is not as bright as the cavernous sinus. Microadenomas will also enhance, but at a slower rate.21 This knowledge is useful in detecting very small lesions because microadenomas appear hypointense relative to the enhancement of the cavernous sinuses and pituitary gland.22

CONCLUSION An ES of normal size <1.200 cm3 on radiography, is a frequent autopsy finding that represents a normal anatomical variant. However, when an ES is enlarged, it is frequently pathologic and should prompt further diagnostic work. The cause of an enlarged ES receiving the most support in the recent literature is that of a pituitary adenoma that has undergone necrosis and/or hemorrhage. In this manner, an enlarged ES actually represents a stage in the spontaneous course of some pituitary adenomas.3 MRI is the diagnostic modality of choice when evaluating the pituitary because of the exquisite definition of soft tissues, high-resolution multiplanar capabilities, and noninvasiveness. The pituitary gland morphology normally varies on MRI depending on the patient’s age and pregnancy status. Both adolescence and pregnancy cause enlargement of the gland, and involution occurs after 50 years of age. Signal intensities also vary. The anterior lobe has a normal high T1w signal intensity until 2 months of age, when it assumes an adult signal intensity, isointense to the pons. The posterior lobe has a high T1w signal intensity due to the storage of secretory granules containing the neurophysin-peptide complex. However, depletion of ADH in dehydrated elderly and diabetes insipidus patients can cause a decreased T1w signal intensity in the posterior lobe. The pituitary does not have a blood-brain barrier and uniformly enhances after contrast injection. Although an enlarged ES is usually associated with a gamut of symptoms ranging from headache to CSF rhinorrhea, this case represents an enlarged ES without symptoms.

REFERENCES 1. Robinson DB, Michaels RD. Empty sella resulting from the spontaneous resolution of a pituitary macroadenoma. Arch Intern Med 1992;152:1920-3.

2. Kaufman B. The “empty” sella turcica—a manifestation of the intrasellar subarachnoid space. Radiology 1968;90:931-41. 3. Bjerre P. The empty sella. A reappraisal of etiology and pathogenesis. Acta Neurol Scand 1990;84(suppl 2):5-24. 4. Latchaw RE, Roppolo HM. Radiographic evaluation of the normal sella turcica and pituitary gland. In: Taveras JM, Ferrucci JT, editors. Radiology: Diagnosis—imaging—intervention; vol 3. Philadelphia: Lippincott-Raven; 1996. p. 1-7. 5. Keats TE. Atlas of roentgenographic measurement. 6th ed. St Louis: Mosby; 1990. p. 115. 6. Yochum TR, Rowe LJ. Measurements in skeletal radiology. In: Yochum TR, Rowe LJ, editors. Essentials of skeletal radiology; vol 1. 2nd ed. Baltimore: Williams & Wilkins; 1996. p. 142. 7. Hollinshead WH, Rosse C, editors. Textbook of anatomy. 4th ed. Philadelphia: Harper & Row; 1985. p. 130-33. 8. Guyton AC. Textbook of medical physiology. 8th ed. Philadelphia: WB Saunders; 1991. p. 819-29. 9. Catarci T, Fiacco F, Bozzao L, Pati M, Magiar AV, Cerbo R. Empty sella and headache. Headache 1994;34:583-6. 10. Terano T, Seya A, Tamura Y, Yoshida S, Hirayama T. Characteristics of the pituitary gland in elderly subjects from magnetic resonance images: relationship to pituitary hormone secretion. Clin Endocrinol (Oxf) 1996;45:273-9. 11. Brodsky MC, Vaphiades M. Magnetic resonance imaging in pseudotumor cerebri. Ophthalmology 1998;105:1686-93. 12. Wakai S, Fukushima T, Teramoto A, Sano K. Pituitary apoplexy: its incidence and clinical significance. J Neurosurg 1981;55:187-93. 13. Braatvedt GD, Corrall RJM. The empty sella syndrome: much ado about nothing. Br J Hosp Med 1992;47:523-5. 14. Elster AD. Modern imaging of the pituitary. Radiology 1993; 187:1-14. 15. Tien RD, Kucharczyk J, Bessette J, Middleton M. MR imaging of the pituitary gland in infants and children: changes in size, shape, and MR signal with growth and development. AJR Am J Roentgenol 1992;158:1151-4. 16. Caruso RD, Rosenbaum AE, Sherry RG, Wasenko JJ, Joy SE, Hochhauser L, Chang JK. Pituitary gland. Variable signal intensities on MRI a pictorial essay. Clin Imaging 1998;22:327-32. 17. Wolpert SM, Osborne M, Anderson M, Runge VM. The bright pituitary gland—A normal MR appearance in infancy. Am J Neuroradiol 1988;9:1-3. 18. Miki Y, Asato R, Okumura R, Togashi K, Kimura I, Kawakami S, Konishi J. Anterior pituitary gland in pregnancy: hyperintensity at MR. Radiology 1993;187:229-31. 19. Holder CA, Elster AD. Magnetization transfer imaging of the pituitary: further insights into the nature of the posterior “bright spot.” J Comput Assist Tomogr 1997;21:171-4. 20. Sato N, Ishizaka H, Yagi H, Matsumoto M, Endo K. Posterior lobe of the pituitary in diabetes insipidus: dynamic MR imaging. Radiology 1993;186:357-60. 21. Sorana M, Kucharczyk W, Wee R. Pituitary microadenomas. In: Taveras JM, Ferrucci JT, editors. Radiology: diagnosis— imaging—intervention; vol 3. Philadelphia: Lippincott-Raven; 1996. p. 10. 22. Hasso AN, Kortman KE, Bradley WG. Supratentorial neoplasms. In: Stark DD, Bradley WG, editors. Magnetic resonance imaging; vol 1. 2nd ed. St Louis: Mosby; 1992. p. 806-9.