- Bony anatomy: The sella turcica ("Turkish saddle") is a concave, midline depression in the basisphenoid that contains the pituitary gland (also called the hypophysis). The anterior borders of the sella are formed by the anterior clinoid processes of the lesser sphenoid wing and the tuberculum sellae, while the posterior border is formed by the dorsum sellae. The top of the dorsum sellae expands to form the posterior clinoid processes, which in turn form the upper margin of the clivus. The floor of the sella is part of the sphenoid sinus roof, which is partially or completely aerated. The cavernous segments of the internal carotid artery (ICAs) lie in shallow grooves, called the carotid sulci, which are located inferolateral to the sella.
- Meninges: The meninges in and around the sella turcica form important anatomic landmarks. Dura covers the bony floor of the sella itself. A thin dural reflection borders the pituitary fossa laterally and forms the medial cavernous sinus wall. A small circular dural shelf, the diaphragma sellae, forms a roof over the sella turcica that, in most cases, almost completely covers the pituitary gland. The diaphragma sella has a variably sized central opening that transmits the pituitary stalk. In some cases, this dural opening is large and gapes widely. In such cases, arachnoid ± accompanying cerebrospinal fluid (CSF) may protrude from the suprasellar cistern inferiorly through the diaphragma sellae opening into the sella turcica and cause the imaging appearance of an empty sella.
- Overview: The pituitary gland, also called the hypophysis cerebri, consists of 3 major parts: The adenohypophysis (AH), the neurohypophysis (NH), and the pars intermedia (PI) plus the infundibulum, which are generally considered together as a unit.
- Adenohypophysis: The AH, also called the anterior lobe, wraps anterolaterally around the NH in a U-shaped configuration. The AH contains acidophil, basophil, and chromophobe cells as well as other cells, such as tanycytes. Cells of the AH secrete trophic hormones (TSH, ACTH, LH, and FSH) as well as growth hormones (GHs). The AH forms 75-80% of the pituitary gland by volume.
- Pars intermedia: The PI is derived from the buccal ectoderm of the embryonic Rathke pouch. It is relatively small (< 5% of the pituitary volume). Axons from the hypothalamus carry granules of releasing hormones to the AH.
- Neurohypophysis: The NH, sometimes called the pars nervosa, consists of the posterior lobe of the pituitary gland, infundibular stem, and median eminence of the hypothalamus. The NH is formed from the embryonic diencephalon (forebrain) as a downward extension of the hypothalamus. Vasopressin and oxytocin are formed within the hypothalamus, pass inferiorly along the hypothalamohypophysial tract, and are stored in the NH. The NH comprises ~ 20% of the pituitary gland.
- MR is generally the imaging procedure of choice. Recommended sequences include precontrast thin-section, small FOV sagittal and coronal T1- and T2WIs followed by postcontrast sagittal and coronal T1WI C+ FS images. Whole-brain FLAIR is a useful sequence to add. T2*/SWI may be helpful in detecting pituitary hemorrhage. If microadenoma is suspected, dynamic imaging with coronal thin-section T1WIs obtained at 5-10 second intervals following rapid bolus injection of contrast are recommended. At least 3 sections (3 mm or less with no interslice gap), sorted by slice, are typically obtained. Some 20-30% of microadenomas are detected only on dynamic contrast-enhanced MR imaging.
- Thin-section coronal CT with sagittal/coronal reconstruction may be a useful imaging adjunct when lesions affecting the sella &/or cavernous sinus arise in the basisphenoid.
- Size: The overall height of the pituitary gland varies with both sex and age. In prepubescent children, 6 mm or less is considered normal. Physiologic hypertrophy, with a normal height of up to 10 mm, is common in young menstruating females. An upwardly convex gland is common in these patients. Pregnant and lactating females can have an even larger gland with a height of 12 mm. The upward limit of normal in adult males and postmenopausal females is 8 mm.
- Signal intensity: Pituitary gland signal varies. With the exception of neonates (in whom the AH can be large and very hyperintense), the AH is typically isointense to gray matter on precontrast T1WIs. A dark or black pituitary gland seen on T2* is found in iron overload states (thalassemia, hemochromatosis). A uniformly white pituitary gland on T1WI is uncommon and can be seen in liver failure.
- The NH usually has a short T1 [posterior pituitary bright spot (PPBS)] likely caused by vasopressin/oxytocin neurosecretory granules. The bright spot does not suppress with FS as it does not contain fat. Although the absence of a PPBS is common in central diabetes insipidus, up to 20% of normal imaged patients lack a PPBS.
- Enhancement: The pituitary gland does not have a blood-brain barrier so it enhances rapidly and strongly following contrast administration. Enhancement is typically slightly less intense than that of venous blood in the adjacent cavernous sinuses.
- Pituitary "incidentalomas" are common on T1WI C+ scans (found in 15-20% of cases). Seen as focal areas of hypointensity within the intensely enhancing pituitary gland, they can be caused by intrapituitary cysts as well as nonfunctioning microadenomas. Both are very common at autopsy. If a pituitary "incidentaloma" does not enhance at all, then a benign nonneoplastic cyst [such as a PI or Rathke cleft cyst (RCC)] is more likely than a microadenoma.
Differential Diagnosis Approach
- Overview: Because the sellar region is anatomically very complex, at least 30 different lesions occur in and around the pituitary gland. They can arise from the pituitary gland or any adjacent structure (brain, 3rd ventricle, meninges, cavernous sinus, arteries, cranial nerves, etc.). At least 75-80% of all sellar/juxtasellar masses are in the "Big 5": Macroadenoma, meningioma, aneurysm, craniopharyngioma, and astrocytoma. All other lesions (e.g., RCCs and arachnoid cysts, germinoma, lymphoma, metastasis, etc.) are each 1-2% or less.
- Keys to diagnosis: Anatomic sublocation is the most important key to establishing an appropriate differential diagnosis. Initially dividing lesions into 3 categories, the (1) intrasellar, (2) suprasellar, and (3) infundibular, is the 1st step.
- The key to determining anatomic sublocation accurately is asking the question, "Can I find the pituitary gland separate from the mass?" If the gland is the mass, the lesion is most likely a macroadenoma. Less likely pathologies that can enlarge the pituitary gland and sometimes appear indistinguishable from macroadenoma include infiltrating lesions, such as sarcoidosis, histiocytosis, hypophysitis, lymphoma, germinoma, and metastasis. If the mass can indeed be identified as separate from the pituitary gland, it is most likely not macroadenoma and arises from structures other than the hypophysis.
- Clinical considerations: Patient age is an important consideration in differential diagnosis. Lesions that are common in children (craniopharyngioma and astrocytoma of the optic chiasm/hypothalamus) are less common in adults, in whom the most common masses are macroadenoma, meningioma, and aneurysm. Macroadenomas are very common in adults but, with the exception of adolescent females, are quite rare in children. Beware: A lesion in a prepubescent male that looks like a macroadenoma usually is not; it is more often nonphysiologic nonneoplastic hyperplasia from end-organ failure.
- Imaging appearance: Imaging appearance can be very helpful in evaluating a sellar/juxtasellar lesion. Is the lesion calcified? Does it appear cystic? Does it contain blood products? Is it focal or infiltrating? Does it enhance?
- Empty sella: Empty sella is seen in 5-10% of patients as an intrasellar CSF collection that flattens the pituitary gland against the sellar floor. Other than empty sella, most intrasellar masses are lesions of the pituitary gland itself.
- Pituitary hyperplasia: Diffuse pituitary enlargement or hyperplasia is common and can be physiologic in young menstruating females and postpartum/lactating women. Less commonly, pituitary hyperplasia occurs as a result of end-organ failure, such as hypothyroidism. Rarely, intracranial hypotension and dural arteriovenous fistulas (dAVFs) cause pituitary enlargement, probably due to passive venous congestion.
- Macro- and microadenomas: The most common "real" intrasellar masses are pituitary microadenomas (defined as < 10 mm) and macroadenomas. Macroadenomas may extend superiorly through the diaphragma sella opening into the suprasellar compartment. Occasionally macroadenomas can appear very aggressive and extremely invasive, extending into the cavernous sinus and eroding the skull base. Pituitary carcinoma is exceptionally rare, typically diagnosed at the time of metastatic spread.
- Miscellaneous lesions: A number of neoplastic and nonneoplastic processes can infiltrate the pituitary gland and adjacent structures, such as neurosarcoid, lymphoma, and metastases.
- Children vs. adults: Once a lesion is defined as suprasellar, patient age is key to the differential diagnosis. Pediatric suprasellar masses are most often either craniopharyngiomas or pilocytic astrocytomas (hypothalamus, optic chiasm). All other lesions, such as germinoma and histiocytosis, are much less common.
- At least 1/2 of all suprasellar masses in adults are upward extensions of macroadenomas through the diaphragma sella. Macroadenomas are typically heterogeneously enhancing masses that may contain cysts or blood products. Macroadenomas often enlarge or remodel the sella turcica. Meningioma and aneurysm are common in adults, accounting for ~ 10% each of all adult suprasellar masses. Both are rare in children. Meningiomas are homogeneously enhancing masses, separate from the pituitary gland. Aneurysms may be identified on MR by a flow void or pulsation artifact. If thrombosed, an aneurysm may have a laminated appearance. CTA or MRA may be helpful in further characterizing a sellar region aneurysm.
- Imaging appearance: Cystic-appearing suprasellar masses are often nonneoplastic [enlarged 3rd ventricle, RCC, suprasellar arachnoid cyst, and inflammatory cysts, such as neurocysticercosis (NCC)]. RCCs may be intrasellar (40%) or suprasellar (60%). RCCs may be asymptomatic or present with pituitary dysfunction, visual changes, or headache. RCCs are noncalcified, nonenhancing, cystic lesions on CT and MR. A helpful clue on MR is the presence of an intracystic nodule. Craniopharyngioma is the most common suprasellar mass in a child and is often known as the 90% tumor; 90% are cystic, 90% are calcified, and 90% enhance. With the exception of craniopharyngioma, cystic-appearing neoplasms are rare in this location. Pilocytic astrocytoma is the overall most common pediatric glial neoplasm in this area. Pilocytic astrocytomas of the optic chiasm/hypothalamus are solid, not cystic (as they often are when they occur in the posterior fossa).
- The presence of calcification is helpful. In older patients, atherosclerosis (cavernous and supraclinoid ICAs), saccular aneurysm, and meningioma are common lesions that calcify as well as craniopharyngiomas. In children, a calcified suprasellar mass is most often a craniopharyngioma. NCC can calcify and may be found in both children and adults, but the suprasellar cistern is a rare location for NCC cysts.
- Hemorrhage into a sellar/suprasellar mass can be detected with T2* imaging or SWI. Hemorrhagic macroadenoma, pituitary apoplexy, and thrombosed aneurysm can show blooming. The pilomyxoid variant of pilocytic astrocytoma is a rare but important cause of a hemorrhagic suprasellar mass in a child or young adult.
Infundibular Stalk Lesions
- Infundibular stalk lesions are a distinct differential diagnosis. The normal infundibular stalk should be 2 mm or less in transverse diameter and taper gradually from top to bottom.
- A "thick stalk" in a child is usually histiocytosis or germinoma. These 2 lesions are also associated with lack of a normal posterior pituitary bright spot. In an adult, neurosarcoid, lymphocytic hypophysitis, lymphoma, and metastasis are more common. Lesions of the infundibulum often present with diabetes insipidus. Enhancement is often unhelpful as the normal infundibulum lacks a blood-brain barrier and enhances intensely following contrast administration. Neurosarcoid may affect the infundibulum only and appear as a thickened, enhancing stalk but more commonly presents with other CNS lesions. Hypophysitis may be related to an autoimmune inflammatory disorder, granulomatous disease, IgG4 related, or drug related. The cancer immunotherapy drug (ipilimumab) has been associated with lymphocytic hypophysitis, which may affect the gland &/or only the infundibulum.
- Yamamoto J et al: Tumor consistency of pituitary macroadenomas: predictive analysis on the basis of imaging features with contrast-enhanced 3D FIESTA at 3T. AJNR Am J Neuroradiol. 35(2):297-303, 2014
Related Differential Diagnoses