Purpose of This PDQ Summary
General Information
Cellular Classification

Lactotroph (PRL-Producing) Adenomas Corticotroph (ACTH-Producing) Adenomas Somatotroph (GH-Producing) Adenomas Thyrotroph (TSH-Producing) Adenomas Gonadotroph (FSH-Producing and/or LH-Producing) Adenomas Plurihormonal Adenomas Nonfunctioning (Endocrine-Inactive) Adenomas Oncocytic Tumors Carcinomas Metastatic Tumors Other Tumors

Stage Information
Treatment Option Overview
Prolactin-Producing Pituitary Tumors

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Adrenocorticotropic Hormone-Producing Pituitary Tumors

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Growth Hormone-Producing Pituitary Tumors

Current Clinical Trials

Nonfunctioning Pituitary Tumors

Current Clinical Trials

Thyrotropin-Producing Tumors

Current Clinical Trials

Pituitary Carcinomas

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Recurrent Pituitary Tumors

Current Clinical Trials

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Changes to This Summary (09/16/2008)
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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pituitary tumors. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board ¹.

Information about the following is included in this summary:

• Signs and symptoms.
• Clinical presentation.
• Cellular classification.
• Staging.
• Treatment options for different types of tumors.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system ² in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version ³, written in less technical language, and in Spanish ⁴.

General Information

Pituitary tumors represent from 10% to 25% of all intracranial neoplasms. Depending on the study cited, pituitary tumors can be classified into three groups according to their biological behavior: benign, invasive adenoma, and carcinoma.[1,2] Adenomas comprise the largest portion of pituitary neoplasms with an overall estimated prevalence of approximately 17%. Only a minority of adenomas are symptomatic.[3] Invasive adenomas, which account for approximately 35% of all pituitary neoplasms, may invade the dura mater, cranial bone, or sphenoid sinus.[4] Carcinomas account for 0.1% to 0.2% of all pituitary tumors.[5,6]

Pituitary adenomas may be classified based on:[7]

1. An anatomical approach, which classifies pituitary tumors by size based on radiological findings. Tumors are divided into microadenomas (i.e., the greatest diameter is <10 mm) and macroadenomas (i.e., the greatest diameter is ≥I0 mm).[3] Most pituitary adenomas are microadenomas. Historically, the most widely used radioanatomical classification was based primarily on a neuroradiological examination including skull x-rays, pneumoencephalography, polytomography, and carotid angiography [8] and subsequently validated by the application of more accurate computed tomography (CT) and magnetic resonance imaging (MRI).

   An MRI scan is now considered the imaging modality of choice for the diagnosis of pituitary disorders because of its multiplanar capability and good soft tissue contrast enhancement.[3] Sagittal T1-weighted images, clearly displaying the anterior and posterior lobes and the stalk on the same plane, and coronal images, displaying the relation between the pituitary and cavernous sinuses, are optimal for identifying a pituitary adenoma. A 3-mm thin slice typically is used to obtain optimal resolution.[9] A CT scan may also be a useful diagnostic tool with coronal scans providing the optimal view;[10] however, CT scans appear to be less sensitive than MRI scans in this application.[11] For each imaging technique, a focal hypointensity within the pituitary gland is considered abnormal and suggestive of an adenoma. An MRI scan is also the best diagnostic imaging choice for pituitary carcinomas; metastases may be found in the cerebral lobes, cerebellum, spinal cord, leptomeninges, and subarachnoid space.[6]

   This radioanatomical classification places adenomas into 1 of 4 grades (I–IV).[1] (See Stage Information ⁵ for more information.) The grades are as follows:

   • Stage I are microadenomas (<1 cm) without sella expansion.
   
   
   
   • Stage II are macroadenomas (≥1 cm) and may extend above the sella.
   
   
   
   • Stage III are macroadenomas with enlargement and invasion of the floor or suprasellar extension.
   
   
   
   • Stage IV is destruction of the sella.
   
   
   



2. Histological criteria, which use:
   • Immunohistological characterization of the tumors in terms of hormone production. Immunocytochemical staining for pituitary hormones generally correlates with hormone serum levels. Twenty percent of pituitary adenomas have no readily identifiable hormone production.
   
   
   
   • Ultrastructural criteria, which can confirm that nonfunctional lesions are of pituitary origin and characterize the cytological differentiation of tumor cells in terms of anterior pituitary cell types.
   
   
   



3. Functional criteria, which are used to define tumors in terms of their endocrine activity. Clinical endocrinologists often use the functional classification of pituitary adenomas and define these tumors based on their hormonal activity in vivo. A retrospective review of the pituitary adenoma literature indicates that prolactinomas are by far the most common form of pituitary adenoma as determined by immunohistochemical criteria; tumors secreting adrenocorticotropic hormone (ACTH), growth hormone (GH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) follow in decreasing frequency.[3,12] Functionally inactive pituitary adenomas, however, comprise approximately 30% to 35% of the pituitary tumors in most series and are the most common type of macroadenoma.[13]

   Using functional criteria, pituitary adenomas can be characterized as:[1]

   • Prolactin-(PRL) producing, also known as lactotroph, adenomas causing hyperprolactinemia and its clinical sequelae.
   
   
   
   • ACTH-producing, also known as corticotroph, adenomas associated with Cushing or Nelson syndromes.
   
   
   
   • GH-producing, also known as somatotroph, adenomas associated with acromegaly and/or gigantism.
   
   
   
   • Rare thyrotropin TSH-producing, also known as thyrotroph, tumors.
   
   
   
   • The large group of clinically nonfunctioning (i.e., the endocrine-inactive) adenomas. This group is comprised predominantly of gonadotroph adenomas. Gonadotroph adenomas synthesize follicle-stimulating hormone-(FSH) and/or LH, or the alpha or beta subunits of these heterodimers. They are usually detected incidentally or because of the presence of neurologic symptoms. Gonadotroph adenomas are inefficient secretors of the hormones they produce, so they rarely result in a clinically recognizable hormonal hypersecretion syndrome.
   
   
   
   • Because of the relative abundance of adenomas that secrete both GH and PRL, the category of mixed adenomas has also become a designation.
   
   
   

   Hormone-secreting pituitary carcinomas may elicit similar signs and symptoms according to the particular hormone that is secreted; they may also produce signs and symptoms related to malignant spread.[6] Because no unequivocal histopathologic features of carcinoma exist, the diagnosis of malignancy is reserved for pituitary neoplasms that have metastasized to remote areas of the central nervous system (CNS) or outside of the CNS.[4,14,15] In a review of 95 cases of pituitary carcinoma, 68% of the cases were found to be hormone-producing and PRL (26%) and ACTH (25%) were the most common hormonal subtypes.[16] Pituitary carcinomas producing GH were the second most common of the hormonal subtypes, and FSH/LH-producing and TSH-producing carcinomas were even more rarely reported. Other reports indicate that as many as 88% of pituitary carcinomas are endocrinologically active, and ACTH-secreting tumors are the most common.[6] Although only 2% to 10% of pituitary adenomas are ACTH-secreting, the percentage of pituitary carcinomas that secrete ACTH is estimated to be much higher at 25% to 34%.[5,16-19] In a series of 15 cases, carcinomas showed a greater tendency toward systemic metastasis than craniospinal metastasis; the rate of systemic metastasis was 71% for PRL-producing cell tumors and 57% for ACTH-producing tumors.[5]

The signs and symptoms commonly associated with pituitary tumors derived from each specific cell type (i.e., prolactinomas, corticotroph adenomas, somatotroph adenomas, thyrotroph adenomas, and nonfunctioning adenomas) are as follows:

1. Signs and symptoms of prolactinomas may include:[20]
   • Headache.
   • Visual field deficits.
   • Oligomenorrhea or amenorrhea.
   • Reduced fertility.
   • Loss of libido.
   • Erectile dysfunction.
   • Galactorrhea in the estrogen-primed female breast.



2. Signs and symptoms of corticotroph adenomas may include:[20]
   • Headache.
   • Visual field deficits.
   • Proximal myopathy.
   • Centripetal fat distribution.
   • Neuropsychiatric symptoms.
   • Striae.
   • Ability to easily bruise.
   • Skin thinning.
   • Hirsutism.
   • Osteopenia.



3. Signs and symptoms of somatotroph adenomas may include:[20]
   • Headache.
   • Visual field deficits.
   • Growth of hands and feet.
   • Coarsening of facial features.
   • Carpal tunnel syndrome.
   • Snoring and obstructive sleep apnea.
   • Jaw growth and prognathism.
   • Osteoarthritis and arthralgia.
   • Excessive sweating.
   • Dysmorphophobia.



4. Signs and symptoms of thyrotroph adenomas may include:[21]
   • Palpitations.
   • Tremor.
   • Weight loss.
   • Insomnia.
   • Hyperdefecation.
   • Sweating.



5. Signs and symptoms of nonfunctioning adenomas (most commonly gonadotroph adenomas) may include:[22]
   • Headache.
   • Visual field deficits.
   • Pituitary insufficiency, which is due to compression of the pituitary stalk or destruction of normal pituitary tissue by the tumor, and predominantly manifests as secondary hypogonadism.
   • Rarely, ovarian overstimulation, testicular enlargement, or increased testosterone levels.

In addition to cell-type specific presentations, pituitary apoplexy (i.e., pituitary adenoma apoplexy), which can result from an acute hemorrhagic or ischemic infarction of the pituitary in patients harboring often unrecognized secreting or nonfunctioning pituitary adenomas, represents another important clinical presentation of pituitary adenomas. In a series analyzing 40 cases of pituitary apoplexy, the presenting signs and symptoms included headache (63%), vomiting (50%), visual field defects (61%), ocular paresis (40%), mental deterioration (13%), hyponatremia (13%), and syncope (5%); in only four cases pituitary tumor was diagnosed prior to presentation.[23] The development of pituitary adenomas may also occur as a component of three familial cancer syndromes: multiple endocrine neoplasia 1 (MEN 1), Carney complex (e.g., cardiac myxomas, spotty skin pigmentation, and tumors of the adrenal gland and anterior pituitary), and isolated familial acromegaly.[20]

A number of other lesions should be considered in the differential diagnosis of sellar masses. Although rare, lymphocytic (i.e., autoimmune) hypophysitis should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum.[24] In addition, the clinician should consider craniopharyngioma and Rathke cleft cyst in the differential diagnosis of pituitary tumors. Sellar masses may also result from tumors that are metastatic to the pituitary. This typically occurs as a part of a generalized metastatic spread and is usually associated with five or more additional metastatic sites, especially osseous; breast and lung cancer are the most common primary neoplasms metastasizing to the pituitary.[25]

References

1. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19 (6): 798-827, 1998.  [PUBMED Abstract]
   
   
2. Landman RE, Horwith M, Peterson RE, et al.: Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature. J Clin Endocrinol Metab 87 (7): 3084-9, 2002.  [PUBMED Abstract]
   
   
3. Ezzat S, Asa SL, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3): 613-9, 2004.  [PUBMED Abstract]
   
   
4. Scheithauer BW, Kovacs KT, Laws ER Jr, et al.: Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65 (6): 733-44, 1986.  [PUBMED Abstract]
   
   
5. Pernicone PJ, Scheithauer BW, Sebo TJ, et al.: Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79 (4): 804-12, 1997.  [PUBMED Abstract]
   
   
6. Ragel BT, Couldwell WT: Pituitary carcinoma: a review of the literature. Neurosurg Focus 16 (4): E7, 2004.  [PUBMED Abstract]
   
   
7. Ironside JW: Best Practice No 172: pituitary gland pathology. J Clin Pathol 56 (8): 561-8, 2003.  [PUBMED Abstract]
   
   
8. Hardy J: Transsphenoidal surgery of hypersecreting pituitary tumors. In: Kohler PO, Ross GT, eds.: Diagnosis and treatment of pituitary tumors: proceedings of a conference sponsored jointly by the National Institute of Child Health and Human Development and the National Cancer Institute, January 15-17, 1973, Bethesda, Md. Amsterdam, The Netherlands: Excerpta medica, 1973, pp 179-98. 
   
   
9. Elster AD: Modern imaging of the pituitary. Radiology 187 (1): 1-14, 1993.  [PUBMED Abstract]
   
   
10. Chambers EF, Turski PA, LaMasters D, et al.: Regions of low density in the contrast-enhanced pituitary gland: normal and pathologic processes. Radiology 144 (1): 109-13, 1982.  [PUBMED Abstract]
    
    
11. Hall WA, Luciano MG, Doppman JL, et al.: Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 120 (10): 817-20, 1994.  [PUBMED Abstract]
    
    
12. McComb DJ, Ryan N, Horvath E, et al.: Subclinical adenomas of the human pituitary. New light on old problems. Arch Pathol Lab Med 107 (9): 488-91, 1983.  [PUBMED Abstract]
    
    
13. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
    
    
14. Della Casa S, Corsello SM, Satta MA, et al.: Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature. Ann Endocrinol (Paris) 58 (6): 503-9, 1997.  [PUBMED Abstract]
    
    
15. Kemink SA, Wesseling P, Pieters GF, et al.: Progression of a Nelson's adenoma to pituitary carcinoma; a case report and review of the literature. J Endocrinol Invest 22 (1): 70-5, 1999.  [PUBMED Abstract]
    
    
16. Kaltsas GA, Grossman AB: Malignant pituitary tumours. Pituitary 1 (1): 69-81, 1998.  [PUBMED Abstract]
    
    
17. Kovacs K, Horvath E: Pathology of pituitary tumors. Endocrinol Metab Clin North Am 16 (3): 529-51, 1987.  [PUBMED Abstract]
    
    
18. Thapar K, Scheithauer BW, Kovacs K, et al.: p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38 (4): 765-70; discussion 770-1, 1996.  [PUBMED Abstract]
    
    
19. Garrão AF, Sobrinho LG, Pedro-Oliveira, et al.: ACTH-producing carcinoma of the pituitary with haematogenic metastases. Eur J Endocrinol 137 (2): 176-80, 1997.  [PUBMED Abstract]
    
    
20. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
    
    
21. Vance ML: Treatment of patients with a pituitary adenoma: one clinician's experience. Neurosurg Focus 16 (4): E1, 2004.  [PUBMED Abstract]
    
    
22. Losa M, Mortini P, Barzaghi R, et al.: Endocrine inactive and gonadotroph adenomas: diagnosis and management. J Neurooncol 54 (2): 167-77, 2001.  [PUBMED Abstract]
    
    
23. Lubina A, Olchovsky D, Berezin M, et al.: Management of pituitary apoplexy: clinical experience with 40 patients. Acta Neurochir (Wien) 147 (2): 151-7; discussion 157, 2005.  [PUBMED Abstract]
    
    
24. Caturegli P, Newschaffer C, Olivi A, et al.: Autoimmune hypophysitis. Endocr Rev 26 (5): 599-614, 2005.  [PUBMED Abstract]
    
    
25. Komninos J, Vlassopoulou V, Protopapa D, et al.: Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 89 (2): 574-80, 2004.  [PUBMED Abstract]
    
    

Cellular Classification

Pituitary adenomas can be classified according to staining affinities of the cell cytoplasm, size, endocrine activity, histologic characteristics, hormone production and contents, ultrastructural features, granularity of the cell cytoplasm, cellular composition, cytogenesis, and growth pattern.[1] Recent classifications, however, omit criteria based on tinctorial stains (i.e., acidophilic, basophilic, and chromophobic) because of the poor correlation between staining affinities of the cell cytoplasm and other pathological features of pituitary tumors, such as the type of hormone produced and cellular derivation.[1,2] A unifying pituitary adenoma classification incorporates the histological, immunocytochemical, and electron microscopic studies of the tumor cells, and stresses the importance of hormone production, cellular composition, and cytogenesis. This classification emphasizes the structure-function relationship and attempts to correlate morphologic features with secretory activity.[1]

Pituitary adenomas are also classified according to size as microadenomas or macroadenomas. Microadenomas are less than 10 mm in their largest diameter, whereas macroadenomas are 10 mm or more in their largest diameter. (See Stage Information ⁵ for more information.) In addition, pituitary adenomas may be distinguished anatomically as intrapituitary, intrasellar, diffuse, and invasive.[1] Invasive adenomas, which account for approximately 35% of all pituitary neoplasms, may invade into the dura mater, cranial bone, or sphenoid sinus.[3]

Lactotroph adenomas secrete prolactin (PRL) and are typically an intrasellar tumor. In women, these adenomas are often small (<10 mm). In either sex, however, they can become large enough to enlarge the sella turcica. These adenomas represent the most common hormone-producing pituitary tumors and account for 25% to 41% of tumor specimens.[4]

The major manifestation of the corticotroph adenoma is secretion of adrenocorticotropic hormone (ACTH), which results in Cushing syndrome. These tumors are initially confined to the sella turcica, but they may enlarge and become invasive after bilateral adrenalectomy (i.e., Nelson syndrome). These adenomas represent the second or third most common hormone-producing pituitary tumors, depending on the series; in one series, these tumors accounted for 10% of all tumor specimens.[1,4]

Somatotroph adenomas produce growth hormone (GH), resulting in gigantism in younger patients and acromegaly in others. Suprasellar extension is not uncommon. These adenomas represent the second or third most common hormone-producing pituitary tumors, depending on the series; in one series these adenomas accounted for 13% of tumor specimens.[1,4]

Thyrotrophadenomas secrete thyroid-stimulating hormone (TSH), also known as thyrotropin, which results in hyperthyroidism without TSH suppression. Many are large and invasive, may be plurihormonal, and secrete both GH and/or PRL.[5] These tumors are rare and account for ≤2% of tumor specimens.[1,4,5]

Gonadotroph adenomas may secrete follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH), or the alpha or beta subunits that comprise these heterodimers, which, depending on gender, may result in ovarian overstimulation, increased testosterone levels, testicular enlargement, and pituitary insufficiency caused by compression of the pituitary stalk or destruction of normal pituitary tissue by tumor. Many gonadotroph tumors, however, are unassociated with clinical or biochemical evidence of hormone excess and may be considered to be nonfunctioning or endocrine-inactive tumors.[6] Functional, clinically detectable gonadotroph adenomas are rare.[7]

Plurihormonal tumors produce more than one hormone. Morphologically, they can be either monomorphous or plurimorphous. Monomorphous plurihormonal adenomas consist of one cell population that produces two or more hormones. The adenoma cells often differ from nontumorous adenohypophysial cells, and their cellular derivation may remain obscure despite extensive morphological studies. Plurimorphous plurihormonal adenomas consist of two or more distinct cell types, and each produces one hormone.[1] Thyrotroph adenomas are often plurihormonal.[5]

These tumors arise from the adenohypophysis and cause symptoms when they extend beyond the sella, which results in pressure on the surrounding structures rather than secretion of a hormonally active substance. Endocrine-inactive adenomas show positive immunostaining for one or more pituitary hormones;[1] however, they are not associated with clinical and biochemical evidence of hormone excess. Gonadotrophic hormones, as detected by antisera to beta-FSH and beta-LH, are present in many clinically nonfunctioning adenomas. Some of these adenomas are recognized by electron microscopy to have gonadotrophic differentiation, but some have characteristics of less well-differentiated cells and resemble the null cells that were initially thought to be undifferentiated precursors of adenohypophysial cells.[7] Endocrine-inactive pituitary adenomas comprise approximately 30% to 35% of the pituitary tumors in most series and are the most common type of macroadenoma.[8]

Oncocytic tumors of the pituitary, also known as pituitary oncocytomas, are characterized by an abundance of mitochondria, which may fill up to 50% of the cytoplasmic area, which is normally around 8%, and obscure other organelles. These tumors are usually unassociated with clinical and biochemical evidence of hormone excess; in some cases, they may be accompanied by various degrees of hypopituitarism and/or mild hyperprolactinemia. Oncocytic change may occur in several other pituitary tumor types.[1]

Pituitary carcinomas are usually endocrinologically functional, and ACTH-producing and PRL-producing tumors are the most frequent.[2,9] The histological and cytological characteristics of pituitary carcinomas vary from bland and monotonous to frankly malignant.[10] Carcinomas show a variable degree of nuclear atypia and cellular pleomorphism, but they also show significantly higher mitotic rates and cell proliferation indices than adenomas.[2] Carcinomas account for 0.1% to 0.2% of all pituitary tumors.[9,11]

Breast and lung cancer are the most common primary neoplasms metastasizing to the pituitary. Although tumors that are metastatic to the pituitary have been reported to be as high as 28% in autopsy series, the majority of metastatic tumors are clinically silent.[12]

Other tumors that arise in the pituitary include craniopharyngiomas, meningiomas, and germ cell tumors; the rare granular cell tumors, pituicytomas, and gangliogliomas; and the even rarer gangliocytomas, lymphomas, astrocytomas, and ependymomas.[2]

References

1. Kovacs K, Horvath E, Vidal S: Classification of pituitary adenomas. J Neurooncol 54 (2): 121-7, 2001.  [PUBMED Abstract]
   
   
2. Ironside JW: Best Practice No 172: pituitary gland pathology. J Clin Pathol 56 (8): 561-8, 2003.  [PUBMED Abstract]
   
   
3. Scheithauer BW, Kovacs KT, Laws ER Jr, et al.: Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65 (6): 733-44, 1986.  [PUBMED Abstract]
   
   
4. Ezzat S, Asa SL, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3): 613-9, 2004.  [PUBMED Abstract]
   
   
5. Teramoto A, Sanno N, Tahara S, et al.: Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment. Acta Neuropathol (Berl) 108 (2): 147-53, 2004.  [PUBMED Abstract]
   
   
6. Snyder PJ: Extensive personal experience: gonadotroph adenomas. J Clin Endocrinol Metab 80 (4): 1059-61, 1995.  [PUBMED Abstract]
   
   
7. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19 (6): 798-827, 1998.  [PUBMED Abstract]
   
   
8. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
9. Ragel BT, Couldwell WT: Pituitary carcinoma: a review of the literature. Neurosurg Focus 16 (4): E7, 2004.  [PUBMED Abstract]
   
   
10. Pernicone PJ, Scheithauer BW: Invasive pituitary adenoma and pituitary carcinoma. In: Thapar K, Kovacs K, Scheithauer BW, et al., eds.: Diagnosis and Management of Pituitary Tumors. Totowa, NJ: Humana Press, 2001, pp 369-86. 
    
    
11. Pernicone PJ, Scheithauer BW, Sebo TJ, et al.: Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79 (4): 804-12, 1997.  [PUBMED Abstract]
    
    
12. Komninos J, Vlassopoulou V, Protopapa D, et al.: Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 89 (2): 574-80, 2004.  [PUBMED Abstract]
    
    

Stage Information

As with other tumors of the central nervous system (CNS), no tumor, nodes, metastases-based American Joint Committee on Cancer classification and staging system for pituitary tumors exists.[1] Pituitary tumors are classified according to size and divided into microadenomas (i.e., the greatest diameter is <10 mm) and macroadenomas (i.e., the greatest diameter is ≥I0 mm).[2] Most pituitary adenomas are microadenomas. The most widely used radioanatomical classification was based primarily on a neuroradiological examination including skull x-rays, pneumoencephalography, polytomography, and carotid angiography.[3] Subsequently validated by the application of more accurate magnetic resonance imaging (MRI) and computed tomography, this radioanatomical classification places adenomas into 1 of 4 grades (I–IV) and has been augmented by additional studies including immunohistochemistry and electron microscopy.[4] Currently, MRI is considered the imaging modality of choice for the diagnosis of pituitary disorders because of its multiplanar capability and good soft tissue contrast enhancement.[2] Because no unequivocal histopathologic features of pituitary carcinoma exist, the diagnosis of malignancy is reserved for pituitary neoplasms that have metastasized to remote areas of the CNS or to outside of the CNS.[5-7]

The radiographical classification for pituitary adenomas is as follows:[3,8]

0: Normal pituitary appearance.

I: Enclosed within the sella turcica, microadenoma, smaller than 10 mm.

II: Enclosed within the sella turcica, macroadenoma, 10 mm or larger.

III: Invasive, locally, into the sella.

IV: Invasive, diffusely, into the sella.

The grading schema for suprasellar extensions is as follows:[3,8]

1. 0 to 10 mm suprasellar extension occupying the suprasellar cistern.
2. 10 mm to 20 mm extension and elevation of the third ventricle.
3. 20 mm to 30 mm extension occupying the anterior of the third ventricle.
4. A larger than 30 mm extension, beyond the foramen of Monro, or Grade C with lateral extensions.

References

1. Brain and spinal cord. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 387-90. 
   
   
2. Ezzat S, Asa SL, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3): 613-9, 2004.  [PUBMED Abstract]
   
   
3. Hardy J: Transsphenoidal surgery of hypersecreting pituitary tumors. In: Kohler PO, Ross GT, eds.: Diagnosis and treatment of pituitary tumors: proceedings of a conference sponsored jointly by the National Institute of Child Health and Human Development and the National Cancer Institute, January 15-17, 1973, Bethesda, Md. Amsterdam, The Netherlands: Excerpta medica, 1973, pp 179-98. 
   
   
4. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19 (6): 798-827, 1998.  [PUBMED Abstract]
   
   
5. Scheithauer BW, Kovacs KT, Laws ER Jr, et al.: Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65 (6): 733-44, 1986.  [PUBMED Abstract]
   
   
6. Della Casa S, Corsello SM, Satta MA, et al.: Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature. Ann Endocrinol (Paris) 58 (6): 503-9, 1997.  [PUBMED Abstract]
   
   
7. Kemink SA, Wesseling P, Pieters GF, et al.: Progression of a Nelson's adenoma to pituitary carcinoma; a case report and review of the literature. J Endocrinol Invest 22 (1): 70-5, 1999.  [PUBMED Abstract]
   
   
8. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   

Treatment Option Overview

The goals of treatment of pituitary adenomas include normalization of hormonal secretion (i.e., normalization of hypersecretion and improvement in hypofunction) and resolution or cessation of the progression of neurological defects. Interventions may include surgery, medical therapy, radiation therapy, or a combination of these modalities. The treatment of choice must be individualized and is dictated by the type of tumor, the nature of the excessive hormonal expression, and whether or not the tumor extends into the brain around the pituitary.[1,2]

The transsphenoidal microsurgical approach to a pituitary lesion is the most widely employed surgical approach to pituitary lesions and represents a major development in the safe surgical treatment of both hormonally active and nonfunctioning tumors.[3-5] Various modifications have been made, including minor modifications, depending on the tumor type.[3] This approach is often successful in debulking tumors, even those that have a significant suprasellar extension. A contraindication to this approach includes tumors with a significant suprasellar extension with an hourglass-shaped narrowing between the intrasellar and suprasellar component; blind attempts to reach the suprasellar tumor may lead to cerebral damage. In addition, an infection in the sphenoid sinus is potentially a contraindication to the transsphenoidal approach. In such cases, craniotomies via a pterional or subfrontal approach may be performed. Rapid deterioration of vision is an immediate indication for surgery to relieve pressure produced by an expanding tumor mass, except in the case of macroprolactinomas (where intensive observation with a patient on dopaminergic agonists may be an acceptable alternative). Progressive deterioration of visual fields is often the primary neurological criterion on which surgical management decisions are based.[6]

Conventional radiation therapy is an effective adjunct to the treatment of pituitary tumors.[3] The advantages of radiation therapy are that it is noninvasive and suitable for surgically high-risk patients. The clinical and biochemical response, however, is slow and may require from 2 years to 10 years for complete and sustained remission. In addition, radiation therapy carries a substantial risk of hypopituitarism (i.e., approximately 30% at 10 years). Stereotactic radiation surgery may be a treatment option for patients with recurrent or residual adenomas.[7]

Hormone-secreting tumors may be treated with surgery or radiation therapy. Surgical therapy is the treatment of choice for growth hormone-(GH) producing, adrenocorticotropic hormone-(ACTH) producing, and endocrine-inactive adenomas. GH-secreting tumors can be treated with somatostatin analogues, dopamine analogues, and the newer GH-receptor antagonists, such as pegvisomant.[6] Ketoconazole, an inhibitor of steroidogenesis, is considered the first drug of choice as adjunctive medical therapy for ACTH-producing tumors.[3] Somatostatin analogues are the drugs of choice for treatment of thyroid-stimulating, hormone-producing adenomas; however, the efficacy of treatment may wane with time.[6]

The natural history of growth hormone-secreting and ACTH-secreting pituitary tumors is usually one of slowly progressive enlargement.[3] Microprolactinomas, however, often remain unchanged, or decrease in size over time, and have been observed to undergo complete, spontaneous resolution on occasion.[6]

Most microprolactinomas and macroprolactinomas respond well to medical therapy with ergot-derived dopamine agonists, including bromocriptine and cabergoline.[6] For many patients, cabergoline has a more satisfactory side-effect profile than bromocriptine. Cabergoline therapy may be successful in treating patients whose prolactinomas are resistant to bromocriptine or who cannot tolerate bromocriptine; this therapy has a success rate of more than 90% in patients with newly diagnosed prolactinomas.[8-10] In a prospective study, cabergoline was safely withdrawn in patients with normalized prolactin levels and no evidence of tumor, which may effect a cure rate of approximately 70%.[11] On the basis of its safety record in pregnancy, however, bromocriptine is the treatment of choice when restoration of fertility is the patient’s goal.[12] Microprolactinomas change little in size with treatment, but macroprolactinomas can be expected to shrink, sometimes quite dramatically. Microprolactinomas may decrease in size over time and have been observed to undergo complete, spontaneous resolution on occasion.[13] Surgery is typically reserved for those patients who cannot tolerate dopamine agonists, who suffer pituitary apoplexy during treatment, or whose macroprolactinomas are not responsive to medical therapy.[6]

Treatment for acromegaly includes surgical, radiation, and medical therapies.[6] Microadenomectomy or macroadenoma decompression is approached transsphenoidally in most patients. Increasingly, endoscopic surgery is used to allow the entire surgical field to be viewed and to allow tumor tissue that would otherwise be inaccessible with rigid instruments to be safely resected. Complete return of GH concentrations to normal, however, is not often achieved. Adjunctive radiation therapy is increasingly reserved for tumors that extend beyond the safe operative area and appear to pose an ongoing threat. Drug treatment includes the use of somatostatin analogues, dopamine analogues, and the GH-receptor antagonist, pegvisomant. As the first of a new class of GH receptors, pegvisomant works by inhibiting functional dimerization of GH receptors, and thereby inhibits GH action. Preliminary results indicate that it may be the most effective medical treatment for acromegaly reported to date.[14,15] In acromegalic patients, impaired glucose tolerance, hypertension, and hyperlipidemia should be vigorously treated concurrently with definitive therapy. A multidisciplinary clinical approach may be required for the treatment of arthritis, carpal tunnel syndrome, obstructive sleep apnea, and prognathism. Mortality is related primarily to cardiovascular and respiratory diseases.[16]

For corticotroph adenomas, transsphenoidal microsurgery is the treatment of choice.[3,6] Remission rates reported in most series are approximately 70% to 90%.[3] In a series of 216 patients who had surgery using a transsphenoidal approach, 75% experienced long-term remission, 21% experienced persistence of Cushing disease, and 9% had recurrence after the initial correction of the hypercortisolism.[17] The average time interval for reoperation was 3.8 years. Seventy-nine percent of the tumors were microadenomas, and 18% were macroadenomas; 86% of the cases with microadenoma had long-term remission, whereas, only 46% of those with macroadenoma had remission. In cases in which hypercortisolemia persists, early repeat exploration and/or radiation therapy or laparoscopic bilateral adrenalectomy may be required.[6] Drug therapy is considered an adjunct to transsphenoidal microsurgery in cases in which there is residual tumor, and in cases in which one is awaiting the effects of the radiation therapy.[3] Ketoconazole, an inhibitor of steroidogenesis, is considered the first drug of choice. Radiation therapy has been used in patients who are deemed to be poor surgical candidates and has also been used as adjunctive therapy in patients with residual or recurrent active tumor.[3] If untreated, patients frequently succumb to cardiovascular disease or infection.

Surgical management is typically considered the first choice of treatment for patients with endocrine inactive pituitary adenomas because of its effectiveness in ameliorating symptoms of chiasmal compression and headache.[18] Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Seventy percent to 80% of patients experience normalization or improvement of visual field defects, and almost 100% of patients with headache as a presenting symptom experience relief. Regrowth of the tumor after radiologically confirmed gross total removal appears to be uncommon. In a series of 32 patients, only 2 (6.2%) with gross total tumor removal and no postoperative radiation therapy showed radiological recurrence of the tumor at a mean follow-up of 5.5 years.[19] Radiation therapy has been administered routinely in the postoperative period and after clear radiologic evidence of residual or recurrent tumor has been demonstrated; drug therapy appears to be of limited value.[18]

Transsphenoidal surgery is the treatment of choice for patients with thyrotroph adenomas.[20] Adjuvant radiation therapy may be employed when surgery is known to be noncurative even if the patient is still euthyroid because relapse is inevitable, and the full effect of radiation requires months or years. Medical therapy may be required for patients who are still hyperthyroid despite surgery and external radiation. Somatostatin analogues are the drugs of choice for treatment; however, the efficacy of treatment may wane with time.[6,20-22]

The initial treatment of patients with gonadotroph adenomas is usually by transsphenoidal surgery, particularly if the adenoma presents with neurological symptoms, because the effect of radiation therapy occurs too slowly, and no reliable medical therapy exists.[23]

Treatment options for patients with pituitary carcinomas include resection and dopamine agonists for prolactin (PRL)-producing tumors; somatostatin analogues for GH-producing and thyroid-stimulating hormone (TSH)-producing tumors; radiation therapy, and chemotherapy.[24] These treatments are palliative with the mean survival time ranging from 2 years to 2.4 years, though several case reports of long-term survivors have been published.[2,25-27]

References

1. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19 (6): 798-827, 1998.  [PUBMED Abstract]
   
   
2. Landman RE, Horwith M, Peterson RE, et al.: Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature. J Clin Endocrinol Metab 87 (7): 3084-9, 2002.  [PUBMED Abstract]
   
   
3. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
4. Hardy J: Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 16: 185-217, 1969.  [PUBMED Abstract]
   
   
5. Hardy J: Transsphenoidal hypophysectomy. J Neurosurg 34 (4): 582-94, 1971.  [PUBMED Abstract]
   
   
6. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
   
   
7. Laws ER, Sheehan JP, Sheehan JM, et al.: Stereotactic radiosurgery for pituitary adenomas: a review of the literature. J Neurooncol 69 (1-3): 257-72, 2004 Aug-Sep.  [PUBMED Abstract]
   
   
8. Colao A, Di Sarno A, Landi ML, et al.: Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 85 (6): 2247-52, 2000.  [PUBMED Abstract]
   
   
9. Cannavò S, Curtò L, Squadrito S, et al.: Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenoma. J Endocrinol Invest 22 (5): 354-9, 1999.  [PUBMED Abstract]
   
   
10. Colao A, Di Sarno A, Landi ML, et al.: Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 82 (11): 3574-9, 1997.  [PUBMED Abstract]
    
    
11. Colao A, Di Sarno A, Cappabianca P, et al.: Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 349 (21): 2023-33, 2003.  [PUBMED Abstract]
    
    
12. Schlechte JA: Clinical practice. Prolactinoma. N Engl J Med 349 (21): 2035-41, 2003.  [PUBMED Abstract]
    
    
13. Ezzat S, Asa SL, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3): 613-9, 2004.  [PUBMED Abstract]
    
    
14. Stewart PM: Pegvisomant: an advance in clinical efficacy in acromegaly. Eur J Endocrinol 148 (Suppl 2): S27-32, 2003.  [PUBMED Abstract]
    
    
15. Muller AF, Kopchick JJ, Flyvbjerg A, et al.: Clinical review 166: Growth hormone receptor antagonists. J Clin Endocrinol Metab 89 (4): 1503-11, 2004.  [PUBMED Abstract]
    
    
16. Colao A, Ferone D, Marzullo P, et al.: Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25 (1): 102-52, 2004.  [PUBMED Abstract]
    
    
17. Mampalam TJ, Tyrrell JB, Wilson CB: Transsphenoidal microsurgery for Cushing disease. A report of 216 cases. Ann Intern Med 109 (6): 487-93, 1988.  [PUBMED Abstract]
    
    
18. Losa M, Mortini P, Barzaghi R, et al.: Endocrine inactive and gonadotroph adenomas: diagnosis and management. J Neurooncol 54 (2): 167-77, 2001.  [PUBMED Abstract]
    
    
19. Lillehei KO, Kirschman DL, Kleinschmidt-DeMasters BK, et al.: Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas. Neurosurgery 43 (3): 432-8; discussion 438-9, 1998.  [PUBMED Abstract]
    
    
20. Brucker-Davis F, Oldfield EH, Skarulis MC, et al.: Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 84 (2): 476-86, 1999.  [PUBMED Abstract]
    
    
21. Caron P, Arlot S, Bauters C, et al.: Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 86 (6): 2849-53, 2001.  [PUBMED Abstract]
    
    
22. Teramoto A, Sanno N, Tahara S, et al.: Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment. Acta Neuropathol (Berl) 108 (2): 147-53, 2004.  [PUBMED Abstract]
    
    
23. Snyder PJ: Extensive personal experience: gonadotroph adenomas. J Clin Endocrinol Metab 80 (4): 1059-61, 1995.  [PUBMED Abstract]
    
    
24. Ragel BT, Couldwell WT: Pituitary carcinoma: a review of the literature. Neurosurg Focus 16 (4): E7, 2004.  [PUBMED Abstract]
    
    
25. Pernicone PJ, Scheithauer BW, Sebo TJ, et al.: Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79 (4): 804-12, 1997.  [PUBMED Abstract]
    
    
26. Sironi M, Cenacchi G, Cozzi L, et al.: Progression on metastatic neuroendocrine carcinoma from a recurrent prolactinoma: a case report. J Clin Pathol 55 (2): 148-51, 2002.  [PUBMED Abstract]
    
    
27. Vaquero J, Herrero J, Cincu R: Late development of frontal prolactinoma after resection of pituitary tumor. J Neurooncol 64 (3): 255-8, 2003.  [PUBMED Abstract]
    
    

Prolactin-Producing Pituitary Tumors

When the pituitary tumor secretes prolactin (PRL), treatment will depend on tumor size and the symptoms that result from excessive hormone production. Patients with PRL-secreting tumors are treated with surgery and radiation therapy.[1] Most microprolactinomas and macroprolactinomas respond well to medical therapy with ergot-derived dopamine agonists, including bromocriptine and cabergoline.[2] For many patients, cabergoline has a more satisfactory side effect profile than bromocriptine. Cabergoline therapy may be successful in treating patients whose prolactinomas are resistant to bromocriptine or who cannot tolerate bromocriptine, and this treatment has a success rate of more than 90% in patients with newly diagnosed prolactinomas.[3-5] On the basis of its safety record in pregnancy, however, bromocriptine is the treatment of choice when restoration of fertility is the patient’s goal.[6] Microprolactinomas change little in size with treatment, but macroprolactinomas can be expected to shrink, sometimes quite dramatically. Surgery is typically reserved for those patients who cannot tolerate dopamine agonists, who suffer pituitary apoplexy during treatment, or whose macroprolactinomas are not responsive to medical therapy.[2] Occasionally, these tumors may ultimately require radiation therapy.[7]

Standard treatment options:[1-7]

1. Dopamine agonists, such as cabergoline and bromocriptine.
2. Surgery (second-line).
3. Radiation therapy (occasionally).

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
2. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
   
   
3. Colao A, Di Sarno A, Landi ML, et al.: Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 85 (6): 2247-52, 2000.  [PUBMED Abstract]
   
   
4. Cannavò S, Curtò L, Squadrito S, et al.: Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenoma. J Endocrinol Invest 22 (5): 354-9, 1999.  [PUBMED Abstract]
   
   
5. Colao A, Di Sarno A, Landi ML, et al.: Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 82 (11): 3574-9, 1997.  [PUBMED Abstract]
   
   
6. Schlechte JA: Clinical practice. Prolactinoma. N Engl J Med 349 (21): 2035-41, 2003.  [PUBMED Abstract]
   
   
7. Nomikos P, Buchfelder M, Fahlbusch R: Current management of prolactinomas. J Neurooncol 54 (2): 139-50, 2001.  [PUBMED Abstract]
   
   

Adrenocorticotropic Hormone-Producing Pituitary Tumors

For patients with corticotroph adenomas, transsphenoidal microsurgery is the treatment of choice.[1,2] Remission rates reported in most series are approximately 70% to 90%.[1] In a series of 216 patients, who were operated on using a transsphenoidal approach, 75% experienced long-term remission, 21% experienced persistence of Cushing disease, and 9% had recurrence after the initial correction of the hypercortisolism.[3] In cases in which hypercortisolemia persists, early repeat exploration and/or radiation therapy or laparoscopic bilateral adrenalectomy may be required.[2] Drug therapy is considered to be an adjunct to transsphenoidal microsurgery in cases with a residual tumor and in cases in which one is awaiting the effects of the radiation therapy.[1] Steroidogenesis inhibitors, including mitotane, metyrapone, ketoconazole, and aminoglutethimide are used. Ketoconazole is the best tolerated of these agents and is effective as monotherapy in about 70% of patients.[4] Radiation therapy has been used in patients who are deemed to be poor surgical candidates and has also been used as adjunctive therapy in patients with residual or recurrent active tumor.[1,5]

Standard treatment options:[1-5]

1. Surgery (the treatment of choice and usually a transsphenoidal approach).
2. Surgery plus radiation therapy.
3. Radiation therapy.
4. Steroidogenesis inhibitors, including mitotane, metyrapone, ketoconazole, and aminoglutethimide.

Treatment options under clinical evaluation:[5-7]

• Stereotactic radiation surgery.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
2. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
   
   
3. Mampalam TJ, Tyrrell JB, Wilson CB: Transsphenoidal microsurgery for Cushing disease. A report of 216 cases. Ann Intern Med 109 (6): 487-93, 1988.  [PUBMED Abstract]
   
   
4. Nieman LK: Medical therapy of Cushing's disease. Pituitary 5 (2): 77-82, 2002.  [PUBMED Abstract]
   
   
5. Mahmoud-Ahmed AS, Suh JH: Radiation therapy for Cushing's disease: a review. Pituitary 5 (3): 175-80, 2002.  [PUBMED Abstract]
   
   
6. Devin JK, Allen GS, Cmelak AJ, et al.: The efficacy of linear accelerator radiosurgery in the management of patients with Cushing's disease. Stereotact Funct Neurosurg 82 (5-6): 254-62, 2004.  [PUBMED Abstract]
   
   
7. Wong GK, Leung CH, Chiu KW, et al.: LINAC radiosurgery in recurrent Cushing's disease after transsphenoidal surgery: a series of 5 cases. Minim Invasive Neurosurg 46 (6): 327-30, 2003.  [PUBMED Abstract]
   
   

Growth Hormone-Producing Pituitary Tumors

Treatment for patients with acromegaly includes surgical, radiation, and medical therapies.[1] Treatment will depend on the size and extent of the tumor and the need for rapid cessation of hormone function that results in serious clinical sequelae (i.e., hypertension and cardiomyopathy). Microadenomectomy or macroadenoma decompression is approached transsphenoidally in most patients. Increasingly, endoscopic surgery is used to allow the entire surgical field to be viewed and to allow tumor tissue that would otherwise be inaccessible with rigid instruments to be safely resected. Complete return of growth hormone (GH) concentrations to normal, however, is not often achieved. Increasingly, adjunctive radiation therapy is reserved for tumors that extend beyond the safe operative area and appear to pose an ongoing threat. Drug treatment, whether used as an adjuvant or primary therapy in appropriately selected patients, which is advocated by some,[2] includes the use of somatostatin analogues, such as octreotide; dopamine analogues, such as bromocriptine; and, the GH-receptor antagonist, pegvisomant. As the first of a new class of GH-receptor antagonists, pegvisomant works by inhibiting functional dimerization of GH receptors and thereby inhibits GH action. Preliminary results indicate that it may be the most effective medical treatment for acromegaly reported to date.[3,4] In acromegalic patients, impaired glucose tolerance, hypertension, and hyperlipidemia should be vigorously treated concurrently with definitive therapy. A multidisciplinary clinical approach may be required for the treatment of arthritis, carpal tunnel syndrome, obstructive sleep apnea, and prognathism.[5]

Standard treatment options: [1,3,4]

1. Surgery (usually a transsphenoidal approach).
2. Bromocriptine.
3. Somatostatin analogues, such as octreotide.
4. The GH-receptor antagonist, pegvisomant.
5. Surgery and postoperative radiation therapy.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
   
   
2. Kleinberg DL: Primary therapy for acromegaly with somatostatin analogs and a discussion of novel peptide analogs. Rev Endocr Metab Disord 6 (1): 29-37, 2005.  [PUBMED Abstract]
   
   
3. Stewart PM: Pegvisomant: an advance in clinical efficacy in acromegaly. Eur J Endocrinol 148 (Suppl 2): S27-32, 2003.  [PUBMED Abstract]
   
   
4. Muller AF, Kopchick JJ, Flyvbjerg A, et al.: Clinical review 166: Growth hormone receptor antagonists. J Clin Endocrinol Metab 89 (4): 1503-11, 2004.  [PUBMED Abstract]
   
   
5. Colao A, Ferone D, Marzullo P, et al.: Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25 (1): 102-52, 2004.  [PUBMED Abstract]
   
   

Nonfunctioning Pituitary Tumors

The selection of treatment for patients with nonfunctioning (endocrine-inactive) tumors will depend on tumor size, the progressive course of the disease, and anatomical structures affected by the tumor extension. The majority of patients present with suprasellar extension and visual field deficits. In addition, many have hormone deficits prior to treatment.Surgical management is typically considered the first choice of treatment for patients with endocrine inactive pituitary adenomas because of its effectiveness in ameliorating symptoms of chiasmal compression and headache.[1] Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Seventy percent to 80% of patients experience normalization or improvement of visual field defects, and almost 100% of patients with headache as a presenting symptom experience relief. Regrowth of the tumor after radiologically confirmed gross total removal appears to be uncommon. Radiation therapy has been administered routinely in the postoperative period and after clear radiological evidence of residual or recurrent tumor has been demonstrated; drug therapy appears to be of limited value.[1-3]

Standard treatment options: [1-3]

1. Surgery (preferably with a transsphenoidal approach) followed by close observation with radiation therapy reserved for recurrence.
2. Radiation therapy.
3. Surgery and postoperative radiation therapy.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Losa M, Mortini P, Barzaghi R, et al.: Endocrine inactive and gonadotroph adenomas: diagnosis and management. J Neurooncol 54 (2): 167-77, 2001.  [PUBMED Abstract]
   
   
2. Tsang RW, Brierley JD, Panzarella T, et al.: Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 30 (3): 557-65, 1994.  [PUBMED Abstract]
   
   
3. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   

Thyrotropin-Producing Tumors

Transsphenoidal surgery is the treatment of choice for patients with thyrotropic adenomas.[1] Adjuvant radiation therapy may be employed when surgery is known to be noncurative even if the patient is still euthyroid because relapse is inevitable, and the full effect of radiation therapy requires months or years. Medical therapy may be required for patients who still have hyperthyroid symptoms despite surgery and external radiation. Somatostatin analogues are the drugs of choice for treatment; however, the efficacy of treatment may wane with time.[1-4]

Standard treatment options:[1-4]

1. Surgery (usually a transsphenoidal approach).
2. Somatostatin analogues, such as octreotide.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Brucker-Davis F, Oldfield EH, Skarulis MC, et al.: Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 84 (2): 476-86, 1999.  [PUBMED Abstract]
   
   
2. Levy A: Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry 75 (Suppl 3): iii47-52, 2004.  [PUBMED Abstract]
   
   
3. Caron P, Arlot S, Bauters C, et al.: Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 86 (6): 2849-53, 2001.  [PUBMED Abstract]
   
   
4. Teramoto A, Sanno N, Tahara S, et al.: Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment. Acta Neuropathol (Berl) 108 (2): 147-53, 2004.  [PUBMED Abstract]
   
   

Pituitary Carcinomas

Some reports indicate that as many as 88% of pituitary carcinomas are endocrinologically active, and adrenocorticotrophin hormone-secreting tumors are the most common.[1] Treatments for patients with pituitary carcinomas are palliative with the mean survival time ranging from 2 years to 2.4 years, though several case reports of long-term survivors have been published.[2-5]

Standard treatment options:[1]

1. Surgery.
2. Dopamine agonists, such as bromocriptine, pergolide, quinagolide, and cabergoline for PRL-producing carcinomas.
3. Somatostatin analogues, such as octreotide for GH-producing and TSH-producing carcinomas.
4. Adjuvant radiation therapy, which does not appear to change the disease's outcome.
5. Chemotherapy, which is of little benefit.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with pituitary tumor ⁶. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Ragel BT, Couldwell WT: Pituitary carcinoma: a review of the literature. Neurosurg Focus 16 (4): E7, 2004.  [PUBMED Abstract]
   
   
2. Pernicone PJ, Scheithauer BW, Sebo TJ, et al.: Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79 (4): 804-12, 1997.  [PUBMED Abstract]
   
   
3. Sironi M, Cenacchi G, Cozzi L, et al.: Progression on metastatic neuroendocrine carcinoma from a recurrent prolactinoma: a case report. J Clin Pathol 55 (2): 148-51, 2002.  [PUBMED Abstract]
   
   
4. Landman RE, Horwith M, Peterson RE, et al.: Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature. J Clin Endocrinol Metab 87 (7): 3084-9, 2002.  [PUBMED Abstract]
   
   
5. Vaquero J, Herrero J, Cincu R: Late development of frontal prolactinoma after resection of pituitary tumor. J Neurooncol 64 (3): 255-8, 2003.  [PUBMED Abstract]
   
   

Recurrent Pituitary Tumors

The question and selection of further treatment for patients who relapse is dependent on many factors, including the specific type of pituitary tumor, prior treatment, visual and hormonal complications, and individual patient considerations.

Standard treatment options:[1-3]

1. Radiation therapy for postsurgical recurrence, which offers a high likelihood of local control.
2. Reirradiation, which provides long-term local control and control of visual symptoms.

Treatment options under clinical evaluation:[4-6]

• Stereotactic radiation surgery.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent pituitary tumor ⁸. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ⁷.

References

1. Kovalic JJ, Grigsby PW, Fineberg BB: Recurrent pituitary adenomas after surgical resection: the role of radiation therapy. Radiology 177 (1): 273-5, 1990.  [PUBMED Abstract]
   
   
2. Tsang RW, Brierley JD, Panzarella T, et al.: Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 30 (3): 557-65, 1994.  [PUBMED Abstract]
   
   
3. Schoenthaler R, Albright NW, Wara WM, et al.: Re-irradiation of pituitary adenoma. Int J Radiat Oncol Biol Phys 24 (2): 307-14, 1992.  [PUBMED Abstract]
   
   
4. Sheehan JP, Kondziolka D, Flickinger J, et al.: Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg 97 (5 Suppl): 408-14, 2002.  [PUBMED Abstract]
   
   
5. Laws ER, Sheehan JP, Sheehan JM, et al.: Stereotactic radiosurgery for pituitary adenomas: a review of the literature. J Neurooncol 69 (1-3): 257-72, 2004 Aug-Sep.  [PUBMED Abstract]
   
   
6. Picozzi P, Losa M, Mortini P, et al.: Radiosurgery and the prevention of regrowth of incompletely removed nonfunctioning pituitary adenomas. J Neurosurg 102 (Suppl): 71-4, 2005.  [PUBMED Abstract]
   
   

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NCI Public Inquiries Office

Suite 3036A

6116 Executive Boulevard, MSC8322

Bethesda, MD 20892-8322

Search the NCI Web site

The NCI Web site ¹⁰ provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator ¹¹. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

Changes to This Summary (09/16/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Purpose of This PDQ Summary ¹²

Editorial changes were made to this section.

More Information

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database ¹³.

  Full description of the NCI PDQ database.

Additional PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment ¹⁴

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment ¹⁵

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care ¹⁶

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) ¹⁷

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention ¹⁸

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics ¹⁹

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine ²⁰

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).