Pituitary Metastases

Introduction

Pituitary metastases are an uncommon manifestation of systemic cancer and usually a marker of terminal disease. With improved survival for various types of cancer and with the use of more sensitive imaging techniques, metastases to the pituitary gland are diagnosed with increasing frequency. Benjamin is credited to have been the first one, in 1857, to describe a case of metastasis to the pituitary gland at autopsy in a patient with disseminated melanoma. Since then, a number of surgical and autopsy series and sporadic case reports have described metastatic tumors to the pituitary.

Metastatic pituitary tumors account for only 1% of pituitary tumor resections. In autopsy series, metastases to the pituitary occur between 1% and 3.6% of patients with malignant tumors. If one considers autopsy series in which both the pituitary and surrounding sella turcica have been evaluated, rates of metastasis as high as 27% have been reported to occur in this area.

Pituitary metastases are often seen in the context of a generalized metastatic spread, usually associated with additional metastatic sites, especially osseous. Typically affected are elderly patients in the sixth or seventh decade of life, with no clear sex predominance. Occasionally, a metastasis to the pituitary gland can be the first manifestation of an occult primary tumor or the only site of metastasis and may, although uncommon, occur in early adulthood.

Primary Neoplasm

Breast and lung cancer are the most common primary neoplasms that metastasize to the pituitary and account for approximately two thirds of pituitary metastases. However, neoplasms from almost every tissue including prostate, renal cell, gastrointestinal cancers, uterine, bladder, and thyroid carcinoma have been reported to metastasize to the pituitary. In approximately 3% of cases, the primary tumor remains undetected despite intensive investigation. It has been hypothesized that in patients with breast cancer, the relatively higher incidence of pituitary metastases can be explained by the prolactin-rich environment of the pituitary, enhancing the proliferation of breast tumor cells. Metastases to a preexisting pituitary adenoma are not that uncommon. In most of the reported cases, the host tumor is a nonfunctioning adenoma, whereas occasional cases have concerned PRL-, ACTH-, and GH-secreting adenomas.

Metastases Located Within the Pituitary Gland

Metastatic deposits can reach the sella via several routes: (1) direct hematogenous spread to the pituitary parenchyma or diaphragma sellae; (2) spread from a hypothalamohypophyseal or infundibulum metastasis through the portal vessels; (3) extension from juxtasellar and skull base metastasis; and (4) meningeal spread through the suprasellar cistern. McCormick et al reviewing location of pituitary metastases in 201 cases, found an involvement of the posterior lobe either alone or in combination with the anterior lobe in 84.6%, whereas only the anterior lobe was affected in 15.4% of cases. The predilection for the posterior lobe is mainly attributed to the lack of direct arterial blood supply of the anterior lobe. The posterior lobe is supplied by the hypophyseal arteries, whereas the anterior lobe is nourished by the portal vessels system. Therefore the anterior lobe is “protected” from metastatic hematogenous spread by the characteristics of the portal circulation supplying it. Another contributing factor is that the posterior lobe has a larger area of contact with the adjacent dura. Metastatic deposits in the anterior lobe are usually the result of contiguous spread from the posterior lobe. The anterior lobe seems to be susceptible to ischemic infarcts and is associated with larger metastatic lesions than the posterior lobe.

Symptoms

In some patients, symptoms related to pituitary metastases may be the first manifestation of a malignant neoplasm. Morita and colleagues and Branch and Laws have noted that, in a significant percentage (56% and 64%, respectively) of patients exhibiting symptoms, the pituitary symptoms were the initial presentation of malignant disease.

The most common presenting symptom of pituitary metastases is diabetes insipidus, reflecting a predominance of metastasis to the posterior lobe. Since early studies, most authors underscore the prevalence of diabetes insipidus in pituitary metastases, reported at 100% in some series. McCormick et al, in their review of 40 symptomatic cases, noted diabetes insipidus in 70%, whereas only 15% had one or more anterior pituitary deficiencies. Diabetes insipidus at presentation is a distinctive feature of pituitary adenomas. Diabetes insipidus is an uncommon presentation symptom of pituitary adenomas even when these tumors reach large size. If not initially present, most patients with pituitary metastases will develop diabetes insipidus during the course of the disease, after invasion of the infundibulum or hypothalamus. Occasionally, diabetes insipidus is transient because regeneration of neurohypophyseal fibers may occur, or intermittent. Corticotroph cell insufficiency may mask the presence of diabetes insipidus until corticosteroid treatment is instituted.

Anterior pituitary insufficiency, although not necessarily evident at presentation, is not uncommon in the course of the disease and has been reported with increasing frequency in more recent studies that have utilized more sensitive laboratory techniques and endocrinological tests. In the series by Morita et al, hypothyroidism and hypoadrenalism were the most frequent types of symptomatic hypopituitarism, with hypogonadism following next. Nevertheless, in exceptional cases, pituitary metastases can occur with a hyperfunctional syndrome. Cushing’s syndrome and acromegaly have been reported in cases of metastasis to a preexisting corticotroph or somatotroph cell adenoma, and in exceptional cases of metastasis originating from primary tumors with ectopic ACTH or GH secretion. Hyperprolactinemia, encountered in 6.3% of pituitary metastases, is attributed to stalk compression, with the exception of metastases to a preexisting prolactinoma. A syndrome of inappropriate antidiuretic hormone secretion has also been described.

Compressive symptoms and nonendocrine symptoms related to invasion of adjacent structures are not uncommon. Headache is frequent and has a multifactorial origin as it can be related to invasion of adjacent structures, stretching of the diaphragma sellae, or ventricular distention. Bitemporal hemianopsia is the most common type of visual field impairment. Infiltration of the adjacent cavernous sinus usually induces cranial nerve III palsy, or less frequently, cranial nerve IV palsy. Facial numbness due to cranial nerve V dysfunction is uncommon. Tumor extension to the septum pellucidum or the frontal lobes may result in cognitive deficits or psychiatric symptoms and in anosmia if the olfactory nerve is affected.

Neuroimaging

Radiological imaging generally has not been fruitful in distinguishing pituitary metastases from adenomas ( Figure 24-1 ) unless other metastatic brain lesions coexist. High-resolution CT and MRI are the imaging methods of choice. Computed tomography usually shows a hyperdense or isodense mass ( Figure 24-1 ), homogeneously or inhomogeneously enhancing (if cystic degeneration, hemorrhage, or necrosis exists) after contrast administration. Magnetic resonance imaging may demonstrate an isointense or hypointense mass on T1-weighted imaging (see Figure 24-2 ), with an usually high-intensity sign on T2-weighted imaging, and homogeneous enhancement after gadolinium administration (see Figure 24-3 and 24-4 ), and absence of high-signal intensity of the posterior lobe on T1-weighted imaging. However, neither of these findings is highly specific for pituitary metastasis. Rapid increase of a sellar tumor with aggressive infiltration of adjacent tissues should raise suspicion of a metastatic lesion. Metastases usually display rapid growth and respect the diaphragm early in their course. Therefore a dumbbell-shaped intrasellar and suprasellar tumor, with a clear indentation at the level of the diaphragma sellae, best seen on sagittal images, is suggestive of a metastasis to the pituitary (see Figure 24-2 ), although this type of radiological feature can also occasionally be seen with benign lesions. Invasion of the infundibular recess by a suprasellar mass ( Figure 24-1 ) favors a metastatic lesion as opposed to a primary adenoma because suprasellar adenomas usually push the infundibular recess posteriorly. Linear enhancement of the infundibulum proximal to the tumor, an unusual finding in pituitary adenomas, can also be observed in the presence of a metastatic lesion.