(25-8) Autopsy dissection of the central skull base shows medially positioned cavernous carotid arteries abutting and slightly compressing the pituitary gland . (Courtesy A. Ersen, MD, B. Scheithauer, MD.)

The infundibular stalk and tuber cinereum of the hypothalamus also lack a blood-brain barrier and enhance on T1 C+ (25-7F).

Pituitary "Incidentalomas"

Focal areas of hypointensity or nonenhancement are common on contrast-enhanced scans of the pituitary gland. They are seen in 15-20% of asymptomatic patients and have been dubbed pituitary "incidentalomas." Most are less than 1 cm in diameter ("microincidentalomas"). They can be caused by benign intrapituitary cysts as well as nonfunctioning microadenomas. Both are common at autopsy.

Although most pituitary "incidentalomas" are unsuspected imaging findings and generally of no clinical significance, recent endocrinologic guidelines recommend that patients with microincidentalomas undergo a thorough history, physical examination, and limited laboratory evaluation (i.e., PRL and IGF-1 levels). Patients with "macroincidentalomas" (more than 1 cm) should be evaluated for hypopituitarism and have formal visual field evaluation if the lesion abuts the optic nerves or chiasm.

If patients do not meet specified surgical criteria for removal, follow-up MR is recommended at 6 months for a "macroincidentaloma," 1 year for a "microincidentaloma," and progressively less frequently thereafter if the "incidentaloma" remains unchanged in size.

Normal Imaging Variants

A number of variants occur in the pituitary gland and around the sella turcica; these should not be mistaken for disease on

(25-9) Axial T1WI shows "kissing" carotids with compressed pituitary gland between them. The posterior pituitary "bright spot" is seen squeezed upward between the carotid arteries.

imaging studies. Not all enlarged pituitary glands are abnormal! Pseudoenlargement of the pituitary gland can be caused by "kissing" carotids or an unusually shallow bony sella. Pituitary hyperplasia can be abnormal, but it can also be physiologic and normal. An empty sella is a common normal variant but can be a manifestation of idiopathic intracranial hypertension (pseudotumor cerebri).

"Kissing" Carotid Arteries

The cavernous internal carotid arteries (ICAs) normally lie lateral to the pituitary gland in the parasellar carotid sulci. Occasionally, the ICAs are positioned medially and actually course inside the bony sella (25-8). These "kissing" carotid arteries may compress the pituitary gland, squeezing it upward and making it appear modestly enlarged. The presence of medially positioned ICAs is highly important in presurgical planning for transsphenoidal hypophysectomy, as normally positioned ICAs are not encountered in this approach

(25-9).

Pituitary Hyperplasia

Terminology

Pituitary hyperplasia is a nonneoplastic increase in adenohypophysial cell number. It can be normal (physiologic) or pathologic.

Etiology

Physiologic Hyperplasia. Physiologic increase in pituitary volume is common and normal in many circumstances. Physiologic hypertrophy of puberty and enlarged pituitary glands in young menstruating female patients is very common

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(25-10) (25-11) (25-12) (25-13). Pituitary gland enlargement secondary to prolactin (PRL) cell hyperplasia also occurs during pregnancy and lactation or in response to exogenous estrogen treatment.

Pathologic Hyperplasia. Pathologic hyperplasia most commonly occurs in response to end-organ failure. Primary hypothyroidism is the most common cause of pathologic pituitary hyperplasia. Thyroid-stimulating hormone cell hyperplasia can be induced by longstanding primary hypothyroidism (25-14). Adrenocorticotrophic hormone (ACTH) cell hyperplasia occurs with hypocortisolism in Addison disease. Gonadotroph hyperplasia occurs as a response to primary hypogonadism (Klinefelter or Turner syndromes).

Pathologic hyperplasia can also be induced by ectopic excess of releasing hormones. Growth hormone (GH) cell hyperplasia occurs with increased growth hormone-releasing hormone secreted by pancreatic islet cell tumor, pheochromocytoma, bronchial carcinoma, and thymic carcinoid tumor.

(25-10) Coronal graphic shows physiologic pituitary hyperplasia. The gland is uniformly enlarged and has a mildly convex superior margin. (25-11) Low-power photomicrograph shows an axial section of a pituitary gland with hyperplasia. The diffusely enlarged anterior lobe dwarfs the neurohypophysis . (Courtesy A. Ersen, MD, B. Scheithauer, MD.)

(25-12) Sagittal T1WI in a

16y girl shows normal upward bulging of the pituitary gland . The sellar floor is intact. Note the normal hyperintensity of the neurohypophysis. (25-13) Coronal T1 C+ in the same patient shows the upwardly convex gland almost touching the optic chiasm . The overall volume of the pituitary gland is almost twice the size of one in a postmenopausal woman.

ACTH cell hyperplasia may be secondary to corticotropinreleasing hormone secretion from a hypothalamic hamartoma (see below), neuroendocrine tumor, or ACTH-dependent Cushing disease. Mammosomatotroph hyperplasia occurs in McCune-Albright syndrome and gigantism.

Pathology

Gross Pathology. The most common physiologic form of pituitary hyperplasia is diffuse PRL cell hyperplasia during pregnancy and lactation. The adenohypophysis is symmetrically enlarged, sometimes nearly twice or three times normal size, but otherwise appears grossly normal.

Clinical Issues

Epidemiology. With the exception of PRL cell hyperplasia in pregnancy, pituitary hyperplasia is rare.

(25-14A) Coronal T1 C+ scan in a prepubescent male patient with hypothyroidism shows pituitary hyperplasia with an upwardly bulging gland that mimics macroadenoma.

Demographics. Most patients are children or young adults. PRL cell hyperplasia is the most common etiology.

Presentation. Symptoms vary with the specific hormone. PRL cell hyperplasia causes hyperprolactinemia, whereas GH cell hyperplasia causes gigantism or acromegaly. ACTH cell hyperplasia causes Cushing disease.

Natural History. Normal physiologic hypertrophy does not require treatment. Pathologic hyperplasia is treated medically, and prognosis is excellent. There is no increase in prevalence of adenoma.

Imaging

Symmetric increase in pituitary gland size and overall volume without focal mass effect or bony erosion is the classic finding.

NECT scans show that the superior margin of the gland is convex upward, measuring 10-15 mm in height. There is no evidence of erosion of the bony sella turcica. Enhancement is strong and generally uniform on CECT.

MR demonstrates an enlarged gland that bulges upward and may even contact the optic chiasm. The enlarged pituitary is isointense with cortex on both T1and T2WI. Dynamic contrast-enhanced MR scans with 2- to 3-mm slice thickness and small field of view show that the gland enhances homogeneously. Occasionally focal nodular enhancement is present, especially with ACTH cell hyperplasia.

Differential Diagnosis

(25-14B) Repeat scan obtained a few weeks following initiation of thyroid hormone replacement shows that the pituitary gland returns to a normal size .

whereas physiologic enlargement is common. Remember: an enlarged pituitary gland in a prepubescent male patient is almost always hyperplasia, not adenoma!

Lymphocytic hypophysitis can cause an enlarged pituitary gland. Lymphocytic hypophysitis is most common in pregnant and postpartum female patients and may be difficult to distinguish from physiologic PRL cell hyperplasia on imaging studies alone. If stalk enlargement is present, hypophysitis is more likely than hyperplasia.

Intracranial hypotension results in pituitary enlargement above the sella turcica in 50% of patients. These patients typically present with headaches related to decreased intracranial CSF pressure. The classic imaging appearance of intracranial hypotension includes diffuse dural thickening and enhancement, downward displacement of the brain through the incisura ("slumping midbrain"), and distension of the venous structures and dural sinuses.

Empty Sella

Terminology

An empty sella (ES) is an arachnoid-lined, CSF-filled protrusion that extends from the suprasellar cistern through the diaphragma sellae into the sella turcica (25-15). An ES is rarely completely "empty"; a small remnant of flattened pituitary gland is almost always present at the bottom of the bony sella, even if it is inapparent on imaging studies. Therefore, the term "partially empty sella" is anatomically more accurate.

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Etiology

An ES can be primary or secondary. A primary empty sella occurs when an unusually wide (sometimes called "incompetent") opening in the diaphragma sellae allows intrasellar herniation of arachnoid and CSF from the suprasellar cistern above into the sella turcica below (25-16). Pulsatile CSF may gradually enlarge and deepen the sella, but the bony lamina dura separating the sella from the sphenoid sinus remains intact (25-17).

A secondary empty sella occurs when pituitary volume is reduced with surgery, bromocriptine therapy, or radiation treatment. Less often, pituitary apoplexy (usually with pituitary macroadenoma) may leave the expanded bony sella largely empty with only a small remnant of infarcted hemorrhagic gland at the posteroinferior aspect of the sella.

(25-15) Graphic depicts primary empty sella with CSF-filled arachnoid cistern protruding inferiorly into the enlarged sella turcica, flattening the pituitary gland posteroinferiorly against the sellar floor. (25-16) Autopsy specimen seen from above shows a wide opening of the diaphragma sellae with CSF-filled sella below. (Courtesy M. Sage, MD.)

(25-17) Sagittal lowpower photomicrograph shows a partially empty sella as an enlarged, mostly CSF-filled sella with the pituitary glandflattened against the sellar floor. (Courtesy W. Kucharczyk, MD.) (25-18) Sagittal T1 image shows a classic empty sella with an enlarged sella turcica in this 58y woman with Cushing syndrome. The pituitary gland is thinned and flattened against the sellar floor .

Rarely, a child with perinatal insult resulting in diffuse neuronal necrosis in the hypothalamus may have a very thin hypophyseal stalk and a partially empty sella.

A rare but important cause of secondary ES is Sheehan syndrome. Sheehan syndrome is one of the most common causes of hypopituitarism in underdeveloped countries. It results from ischemic pituitary necrosis due to severe postpartum hemorrhage. The great majority of patients with Sheehan syndrome have an empty sella on CT or MR scan.

Clinical Issues

Epidemiology. The exact prevalence of ES is unknown. An ES is identified in 5-10% of cranial MR scans.

Demographics. Although ES can occur at any age, peak presentation is in the fifth decade. There is a 4:1 female predominance. The mean body mass index of patients with an

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empty or partially empty sella is significantly higher than of those without an ES.

Presentation. Most patients with ES are asymptomatic or have nonspecific symptoms such as headache (25-19). However, primary ES may be associated with various clinical conditions ranging from mild endocrine disturbances to rhinorrhea or otorrhea. Between 18-20% of patients with primary ES have hyperprolactinemia, 5% have global anterior hypopituitarism, and 4% have isolated GH deficiency. Almost 80% of middle-aged obese women with spontaneous CSF otorrhea or rhinorrhea have an associated ES demonstrated on preoperative MR (25-20). Patients with idiopathic intracranial hypertension commonly have an associated partially empty sella (25-21).

Occasionally, patients present with visual disturbances caused by inferior displacement of the optic chiasm into the ES. Most such cases are secondary ES following transsphenoidal hypophysectomy for pituitary adenoma resection.

(25-22A) Sagittal T1 C+ MR image in a 73y man shows an arachnoid cystfilling the sella and suprasellar regions. Note the superior displacement of the infundibulum . The enhancing pituitary gland is flattened anteriorly within the sella turcica . (25-22B) Coronal T1WI in the same patient shows that the optic chiasm is displaced superiorly by the arachnoid cyst . The cyst follows CSF signal intensity on all MR sequences.

(25-23A) Sagittal T1WI shows a very large cystic mass filling the sella and suprasellar regions with mass effect on the adjacent brain. Note the enlarged, flattened sella turcica . (25-23B) Sagittal T2WI in the same patient shows that the arachnoid cyst follows CSF signal intensity . There was no enhancement of this cyst and no intracystic nodule to suggest a Rathke cleft cyst. Following cyst removal, the pituitary function returned to normal.

Treatment Options. Primary and secondary ES generally do not require definitive treatment. Hormone replacement may be needed in some cases. CSF rhinorrhea/otorrhea or optic chiasm displacement with severe visual compromise may necessitate surgical intervention.

Imaging

General Features. Imaging studies show intrasellar CSF with a thinned pituitary gland flattened against the sellar floor.

CT Findings. CSF-density fluid fills a sella that may be of normal size or moderately enlarged. The bony floor of the sella is intact in primary ES, but, in secondary ES, it often shows a surgical defect caused by transsphenoidal hypophysectomy. The infundibular stalk and pituitary remnant enhance normally on CECT scans. The stalk may be displaced off midline, appearing somewhat "tilted."

MR Findings. The intrasellar fluid behaves exactly like CSF on T1and T2WI and suppresses completely on FLAIR. DWI shows no diffusion restriction. In severe cases, the optic chiasm and/or anterior third ventricle may appear herniated into—or retracted toward—the sella. If the ES is secondary to surgery, fat packing and scarring with adhesions may distort the imaging findings.

Differential Diagnosis

The major differential diagnosis of an ES is a suprasellar arachnoid cyst that may herniate into the sella turcica. The bony sella is often not simply enlarged but eroded and flattened. Although arachnoid cysts are often incidental, they are variably sized and usually become symptomatic when large, resulting in mass effect on the pituitary infundibulum and gland. Arachnoid cysts follow CSF signal intensity on all MR sequences and completely suppress on FLAIR images. Sagittal T2WI often shows an elevated, compressed third

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ventricle draped over the suprasellar arachnoid cyst (25-22) (25-23).

The other major consideration of patients with an ES is idiopathic intracranial hypertension (IIH), also known as "pseudotumor cerebri." Both incidental ES and patients with IIH have an increased prevalence in obese female patients. Imaging findings also show some overlap, as both conditions often demonstrate an empty sella. In IIH, the optic nerve sheaths are often dilated, and the ventricles and CSF cisterns often appear smaller than normal. Patients with IIH will also typically have papilledema, which can be seen on MR as protrusion of the optic nerve papilla into the posterior globes

(25-21).

Increased intracranial pressure (↑ ICP) caused by obstructive hydrocephalus usually results in displacement of the enlarged anterior third ventricle recesses—not the suprasellar cistern—toward or into the bony sella. Transependymal CSF migration is common in ↑ ICP but absent in ES.