Imaging Technique

MRI evaluation of the pituitary and parasellar region is best undertaken on modern 1.5-T or 3-T scanners using a protocol that includes both noncontrast and gadolinium-enhanced sequences. Sagittal and coronal planes are most useful, using 3-mm or thinner slices without any interslice gap to adequately evaluate small structures that may be involved in the diseases that occur in this region.

The intrinsic composition of lesions, as characterized based on their T1-weighted and T2-weighted relaxation properties without contrast, usually differs significantly from the pituitary gland, cerebrospinal fluid (CSF), and brain because of the presence of intralesional fluid, protein, hemorrhage, or tumor. Imaging performed after the administration of gadolinium chelate may increase contrast between abnormalities and normal tissues, show otherwise occult disease, and allow one to more confidently differentiate between solid and cystic lesions. Fat suppression is recommended for both T2-weighted and gadolinium-enhanced images, as normal high T2 and T1 signal within the bones of the central skull base may obscure a pathologically high T2 signal or enhancement.

In addition to T1-, T2-, and gadolinium-enhanced T1-weighted images, dynamic contrast-enhanced imaging, gradient-echo T2∗-weighted imaging, and diffusion-weighted imaging play an important role in the diagnosis of certain disorders and should be added when these disorders are suspected. These abnormalities are discussed individually in subsequent sections.

Normal MRI Appearance of the Pituitary and Infundibulum

The identification of abnormalities in the sella and parasellar region requires familiarity with normal anatomy and biological variability. The normal size of the gland varies with age, measuring up to 12 mm in height in lactating women, 10 mm in menstruating women, 8 mm in males and postmenopausal women, and 6 mm in infants ( Table 1 ).

The anterior aspect of the gland, or adenohypophysis, comprises roughly 70% of its volume, and should appear uniform in signal on both unenhanced and enhanced images. Posteriorly within the gland, the neurohypophysis exhibits intrinsic T1 hyperintensity on unenhanced images referred to as the posterior pituitary bright spot (PPBS). The pituitary stalk comprises pars tuberalis cells from the adenohypophysis that surround neurohypophyseal axons descending from the hypothalamus. The normal pituitary infundibulum is wider at its origin from the hypothalamus and tapers inferiorly, reaching its minimum thickness at the level of the pituitary gland. The upper limit for stalk thickness has been reported as 3.5 mm near the median eminence, 2.8 mm at its midpoint, and 2.0 mm at its most inferior aspect. In children, the maximum thickness of the infundibulum is somewhat less, around 2.5 mm.

Interpretative Strategy

A systematic approach to image interpretation is required to develop an accurate differential diagnosis for lesions within or intimately associated with the pituitary gland and/or infundibulum. Key considerations include the following:

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  Verification of the normal imaging appearance of the gland and infundibulum, noting its size, enhancement pattern, and presence or absence of the PPBS

  
  
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  Localization of abnormalities as entirely intrasellar, both sellar and intrasellar, or entirely suprasellar, and as within or separate from the pituitary gland

  
  
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  Characterization of lesions as entirely solid, entirely cystic, or mixed solid and cystic

  
  
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  Evaluation of lesion margins (circumscribed or invasive), morphology, and relationship to the normal pituitary

  
  
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  Distinguishing imaging features that are unique or highly suggestive of certain lesions, such as cysts, low T2 signal, calcification, and fluid-fluid levels

  
  
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  Presence or absence of mass effect on the optic apparatus, invasion of the cavernous sinuses, and abnormalities located elsewhere in the brain

Pituitary Adenoma

Adenoma is the most common abnormality of the pituitary gland and represents 15% of all intracranial neoplasms. It is a slowly growing, benign tumor that almost exclusively arises within the sella and occasionally from the pituitary stalk. Adenomas are rarely found in ectopic sites such as the sphenoid sinus, nasopharynx, cavernous sinuses, and sphenoid bone. Whereas small tumors become clinically manifest owing to excess hormone secretion, larger tumors are more frequently nonsecreting, and tend to present with symptoms related to compression of adjacent structures or elevated intracranial pressure.

Prolactin-secreting and growth hormone–secreting adenohypophyseal cells are located more laterally within the normal pituitary gland and corticotropin-secreting, thyroid-stimulating hormone–secreting, and gonadotropin-secreting cells are located more medially. This inherent spatial organization of adenotrophs within the gland imparts a similar spatial distribution to the origin of hormone-secreting adenomas. Pathologically, adenomas are circumscribed and contained within a pseudocapsule of compressed surrounding pituitary tissue, or are locally invasive, equipped on a molecular basis with microscopic machinery that facilitates contiguous spread through the dura into adjacent bone or cavernous sinus.

Microadenomas, tumors that measure less than 1 cm in diameter, exhibit T1 signal on MRI that is the same as or lower than the gland signal unless intratumoral hemorrhage is present ( Fig. 1 ). T2 signal is more variable. Most tumors exhibit high T2 signal, and tend to be softer and more readily resected at surgery. Low-T2–signal tumors are less common, but as a group tend to be firmer and more adherent to surrounding tissue on surgical manipulation. Approximately 80% of prolactinomas have high T2 signal, and between 40% and 60% of growth hormone–secreting adenomas have low T2 signal. Most tumors are round or discoid in morphology. Subtle contour deformity of the pituitary gland may be present, as may displacement of the infundibulum. The direction of infundibular displacement is usually opposite the side of the tumor, but this finding is only variably seen and is considered unreliable.

Microadenoma. Subtle intrinsic low T2 signal in the right lobe of the pituitary ( A ), seen to better advantage on gadolinium-enhanced T1-weighted image as hypoenhancing relative to the surrounding gland ( B ). This growth hormone–secreting microadenoma appears relatively T2 hypointense compared with normal adenohypophyseal tissue ( C ).

Following administration of intravenous gadolinium chelate, microadenomas are relatively hypoenhancing or isoenhancing relative to the normal pituitary gland during the wash-in phase of contrast. Dynamic imaging, whereby high-resolution pituitary images are obtained immediately following bolus injection of contrast, is useful for illustrating the differential uptake of contrast between a microadenoma and normal pituitary gland, and is used to enhance sensitivity to small tumors by up to 10%. Some tumors retain contrast on delayed imaging more avidly than does the gland, such that MRI obtained during the washout phase of contrast may also increase sensitivity, revealing tumors as hyperenhancing relative to the gland.

Tumors larger than 1 cm are referred to as macroadenomas or, if larger than 4 cm, giant adenomas. Slow tumor growth results in progressive enlargement of the sella. The direction of growth is variable. Approximately 80% extend superiorly into the suprasellar cistern, but the remaining 20% grow in any of the remaining 5 directions to invade the cavernous sinuses, sphenoid sinus, or dorsum sella. MRI often reveals more heterogeneous intrinsic signal than microadenoma on both T1-weighted and T2-weighted images, especially when internal tumor cysts, necrosis, and/or hemorrhage develop within the tumor ( Fig. 2 ). Enhancement is moderate to avid; rare hypoenhancement has been described as a feature of thyrotropin-secreting tumors. The normal pituitary gland, often compressed around large adenomas, is important to identify preoperatively, as preservation of this tissue is a surgical goal in preventing pituitary insufficiency. The PPBS may be difficult to see or even absent, although it is rare for patients with macroadenoma to have central diabetes insipidus (DI).

Macroadenoma. “Dumbbell” or “snowman” appearance of a typical macroadenoma, which shows a narrower waist as it passes through the sellar diaphragm ( A ). Larger macroadenomas are frequently more heterogeneous and contain areas of cystic degeneration ( B ). Tumor growth in adenomas occurs in any direction and may be dramatic, as illustrated in this case in which the superior tumor extends into the third and left lateral ventricle ( C ).

Pituitary apoplexy is due to acute intratumoral hemorrhage or bland tumor infarction. Although uncommon, it is a surgical emergency with specific features on MRI. The term apoplexy refers to the clinical syndrome that results when hemorrhage causes compression of parasellar structures, especially the optic nerve or chiasm, and/or meningismus. Acute presentation distinguishes this entity from subclinical tumoral hemorrhage, a more common phenomenon referred to as silent apoplexy by some investigators. It is also considered a separate entity from postischemic pituitary hemorrhage in patients with prolonged hypotension, referred to as Sheehan syndrome and classically occurring in women with severe postpartum bleeding. Both are more common in patients with known adenomas.

As rapid loss of vision or acute cranial neuropathy may occur, any mass effect on the optic chiasm should be sought on imaging and discussed as an indication for emergent neurosurgical decompression. Subarachnoid and retroclival hemorrhage may also be present. MRI in the acute setting may be subtle, particularly on the routine T1-weighted images. If blood is present, this appears as intratumoral heterogeneous signal and occasionally fluid-fluid levels, which may be T1 hyperintense owing to the presence of methemoglobin. T2-weighted images typically show hypointensity within hemorrhagic areas, which evolves with time into hyperintensity. T2∗-weighted gradient-echo images are more sensitive to the presence of blood products and may demonstrate areas of “blooming,” signal loss around areas of hemorrhage. CT is useful to confirm the presence of blood products in acute or equivocal cases.

Nonadenomatous Tumors of the Pituitary Gland

Pituicytomas are histologically benign, World Health Organization Grade 1 tumors derived from pituicytes, populations of astroglial cells in the posterior pituitary and stalk that assist in the regulation of oxytocin and vasopressin secretion. The controversial pathology of these rare tumors is evident from the range of names they have been assigned, including infundibuloma, choristoma, and pilocytic astrocytoma of the neurohypophysis. Clinical presentation varies with location, with sellar tumors most commonly found incidentally or as a result of hypopituitarism, and suprasellar tumors usually present with visual symptoms related to mass effect.

Although most pituicytomas are located in the suprasellar cistern or have both sellar and suprasellar components, it is the only nonadenomatous primary pituitary tumor that has been reported with a purely intrasellar presentation. The tumor is solid and frequently infiltrative, and inseparable from the pituitary gland. Intrinsic signal on MRI is isointense to cortex on unenhanced T1-weighted images and hyperintense to cortex on T2-weighted images. Pituicytoma is more vascular than adenoma, and enhancement is more frequently uniformly homogeneous than heterogeneous. Primarily because of their posterior location and vascularity, gross total resection of pituicytomas may be difficult or impossible.

Spindle-cell oncocytoma and granular cell tumor of the neurohypophysis are pathologically distinct nonadenomatous tumors of the pituitary gland that are less common even than pituicytoma. The former arises from the adenohypophysis, is commonly both sellar and suprasellar, and is radiologically indistinguishable from the far more common adenoma or lymphocytic hypophysitis. Granular cell tumors, in contradistinction, arise from the neurohypophysis and are entirely suprasellar in most cases, with a smaller number reported with simultaneous sellar and suprasellar location. Hyperdensity on CT may also be a useful distinguishing feature.

Pituitary Carcinoma

Unlike locally invasive adenomas, pituitary carcinomas are rare, with a reported incidence of only 0.2%. These tumors arise from the adenohypophysis and are frequently hormonally active, most commonly secreting corticotropin, prolactin, or growth hormone. Pituitary carcinomas are indistinguishable from adenomas using histologic criteria, and are currently diagnosed only when systemic or craniospinal metastatic disease is identified.

Most pituitary carcinomas present initially as invasive macroadenomas greater than 1 cm in size, demonstrate an aggressive course with rapid growth and multiple recurrences, and are typically diagnosed as carcinomas some 4 to 7 years later when metastases are identified. Central nervous system (CNS) metastases, which are less common than systemic metastases, usually involve the cortex, the cerebellum, the cerebellopontine angle, or the CSF. Outside of the CNS, the liver, lymph nodes, bones, and lung are the most frequent sites of disease. Although most pituitary carcinomas are locally invasive, there are no distinguishing features by imaging save for the presence of metastatic disease.

Pituitary Hyperplasia

Pituitary hyperplasia is a nonneoplastic, polyclonal proliferation of one or more functionally distinct adenohypophyseal cells that results in enlargement of the gland. Hyperplasia can be physiologically normal, for example during pregnancy or lactation, or may be pathologic, either primary or secondary to endocrine gland failure. Most cases are found in hypothyroid patients, in whom the lack of thyroxine from the nonfunctioning thyroid gland results in overproduction of hypothalamic thyrotropin-releasing hormone. Excess of this hormone, in turn, stimulates the pituitary to produce thyroid-stimulating hormone but also results in excess prolactin secretion. Clinically the symptoms of hypothyroidism may be minimal, and masked by symptoms of hyperprolactinemia. MRI in pituitary hyperplasia shows symmetric enlargement of an otherwise normal-appearing, homogeneously enhancing gland ( Fig. 3 ). The gland may be mildly or markedly enlarged, and can occasionally enlarge to a point at which adjacent structures including the optic chiasm are compressed. However, in contrast to macroadenoma, there is no remodeling of the sella, and the gland homogeneously enhances.

Pituitary hyperplasia ( A , B ) and lymphocytic hypophysitis ( C , D ). Both T2-weighted ( A ) and gadolinium-enhanced T1-weighted ( B ) images show enlargement the pituitary gland with uniform T2 signal intensity and enhancement, without sellar enlargement, in a 28-year-old woman presenting with hyperprolactinemia and hypothyroidism. ( C , D ) Two cases of lymphocytic hypophysitis, one with infundibular thickening ( C ) and the other showing heterogeneous enhancement within an enlarged pituitary gland ( D ). In D , note subtle thickening of the sellar diaphragm with adjacent “tails” of inflammatory dural enhancement anterior and posterior to the gland along the planum sphenoidale and dorsum sellae.

Lymphocytic Hypophysitis

Lymphocytic hypophysitis is an autoimmune disorder of the pituitary gland that occurs 5 to 8 times more frequently in women than in men, often occurring in the time period 6 months before to 6 months after pregnancy. Clinically, patients present with hypopituitarism, pituitary insufficiency, DI, and/or symptoms related to mass effect on surrounding structures. Many patients have a personal or family history of autoimmune disease, such as Hashimoto or Graves thyroiditis, systemic lupus erythematosus, or primary biliary cirrhosis. The disease is associated with HLA DR4 and DR5.

MRI findings mirror microscopic pathology, which shows edema and infiltration of the pituitary gland by lymphocytes and plasma cells with areas of glandular fibrosis. Although neurohypophysisitis has been described, the disease is more often confined to the adenohypophysis. The normal PPBS may be absent. The pituitary gland and/or infundibulum may be enlarged within a normal volume sella (see Fig. 3 ). Uncommonly, inflammation may be cystic or necrotic, resulting in areas with higher T2 signal and hypoenhancement within the pituitary. Enhancement may be homogeneous or heterogeneous, and an adjacent enhancing dural tail (thought to represent enhancement of adjacent inflamed diaphragma sellae) is a useful secondary finding. Inflammation infrequently extends to secondarily involve the clivus and/or cavernous sinuses, where narrowing of the lumen of the internal carotid arteries can occur.

Because of its relative infrequency, lymphocytic hypophysitis is often mistaken on MRI for adenoma or other disorders. Symmetric suprasellar extension and midline pituitary stalk position help to differentiate this disorder from adenoma. Nakata and colleagues have also recently described low signal on T2-weighted images around the pituitary gland and in the cavernous sinus as uncommon but highly specific to lymphocytic hypophysitis. Although the disease usually responds to immunotherapy, the natural history is usually one of multiple remissions and relapses.