Pituitary Tumors in Children and Adolescents

Antony R. Lafferty and George P. Chrousos

Section of Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address correspondence and requests for reprints to: Antony R. Lafferty MB ChB, Clinical Associate, Pediatric Endocrinology Section, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862


    Introduction
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 
Tumors occupying the pituitary fossa are of two main types: craniopharyngiomas, the most common tumor causing hypopituitarism in childhood, and pituitary adenomas. Virtually all tumors of this region are benign. Tumors that metastasize to the pituitary during childhood are exceedingly rare. Neoplastic or infiltrative processes of the pituitary area, including gliomas arising from the optic chiasm and surrounding region, meningiomas, germ cell tumors arising from the pituitary stalk, and granulomatous diseases that include histiocytosis X, tuberculosis, and sarcoidosis, may interfere with pituitary function. This review will focus on neoplastic diseases that arise from the pituitary gland or its anlagen.


    Craniopharyngioma
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 
Craniopharyngiomas account for 80–90% of neoplasms arising in the pituitary region. They originate from squamous rest cells in the remnant of Rathke’s pouch between the adenohypophysis and neurohypophysis. Rathke’s pouch is a cystic diverticulum from the roof of the embryonic mouth that gives rise to the adenohypophysis. Tumors may be completely intrasellar (25%) where they may radiologically mimic a pituitary adenoma, solely extrasellar, or a combination of both. Although craniopharyngiomas may arise at any time in life, there is a bimodal peak in incidence at 5–14 yr of age and again after the age of 50 (1). The overall incidence of craniopharyngiomas in the United States is 1.3 per 106 person years and does not seem to vary with race or gender (1).

Although histologically benign, craniopharyngiomas can be aggressive, sending papillae that invade surrounding bony structures and tissues. In addition, they commonly have cystic components that may be multiple and may enlarge, causing compression of adjacent neurological structures.

Presentation

Craniopharyngiomas commonly present with nonendocrine symptoms, such as headache and visual disturbance and, less commonly, with manifestations of endocrine deficiency such as poor growth. Most headaches probably arise from stretching of the diaphragma sellae by the enlarging mass; obstruction of the aqueduct of Sylvius or the foramina of Monro is a rare complication.

Up to 80% of patients have evidence of endocrine dysfunction at diagnosis (2). GH deficiency is the most frequent finding, present in up to 75% of patients, followed by gonadotropin deficiency in 40%, and ACTH and TSH deficiency in 25%. Despite craniopharyngiomas frequently being large at presentation, the pituitary stalk is not commonly disrupted, with only 20% of patients having hyperprolactinemia secondary to pituitary stalk compression. Loss of posterior pituitary function is also uncommon, with 9–17% of patients presenting with diabetes insipidus (3, 4).

Many of the published series of craniopharyngiomas came from the pre-computed tomography (CT) and magnetic resonance imaging (MRI) era when plain skull x-rays were used for diagnosis and tumors were advanced at the time of presentation. Given the low threshold for performing central nervous system imaging in patients with headaches, the natural history of this disease may be changing.

Treatment

Surgery is the treatment of choice for craniopharyngioma, and, ideally, total resection of the tumor. In all but small, totally intrasellar or circumscribed tumors for which total resection is possible it is clear that surgical management alone carries an unacceptably high rate of recurrence and adjunctive radiotherapy should be given.

The treatment-associated morbidity is dependent on the size and invasiveness of tumor at diagnosis, the experience of the surgeon, and the route of surgical approach. The risk of hypothalamic damage is significantly greater in large invasive tumors when aggressive attempts are made at transcranial eradication. Near total excision of the tumor by an experienced pituitary surgeon sparing the hypothalamus, carotids, and visual apparatus, followed by fractionated radiotherapy provides the best hope of low long-term morbidity and longer survival (5, 6, 7, 8). Regardless of the approach, the incidence of endocrine dysfunction is high following surgical treatment (5, 9), although less when a transsphenoidal approach is used (7). Adjunctive localized intracavity Yttrium, 32P, and other radioactive implants have proven useful for recurrent tumors that are predominantly cystic. Hyperfractionated multiportal stereotactic radiotherapy and gamma knife radiosurgery provide promise for the future, given their apparent ability to reduce treatment-associated morbidity in this condition.


    Pituitary Adenomas
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 
Pituitary adenomas comprise 2.7% of supratentorial tumors in childhood, or approximately 3.5–6% of all surgically treated pediatric pituitary tumors (10) (Table 1Go). With the exception of the multiple endocrine neoplasia syndromes, and plurihormonal tumors, most pituitary adenomas probably result from a clonal event in a single cell (11). Pituitary carcinomas are rare in adults (12) and extremely rare in children. The most frequently seen adenoma in children is the prolactinoma, followed by corticotropinoma and then somatotropinoma. Nonfunctioning pituitary adenomas are rare in children accounting for only 3–6% in two large series (13, 14), compared with about one third of patients in adult pituitary tumor series.


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Table 1. Pituitary tumors in children and adolescents

 
Minderman and Wilson (14) reported a large retrospective review of 136 patients less than 20 yr of age who had undergone pituitary surgery at the University of California–San Francisco (San Francisco, CA) between 1969 and 1993. Subjects were stratified into pre-, peri-, and postpubertal groups (14). Only one quarter of pediatric patients with pituitary adenomas presented before age 12. Overall, the most frequent type of adenoma was the prolactinoma, accounting for 53% of all tumors, although 93% of them presented in children older than 12 yr. Corticotropinomas were the commonest tumor seen prepubertally although they occurred at all ages (13, 14).

The T1 weighted spin-echo MRI of the pituitary before and after administration of gadolinium (Gd) is the imaging modality of choice for detecting pituitary adenomas. Coronal and sagittal images should be obtained at 3-mm intervals before and after contrast, focusing on the pituitary region rather than imaging the whole brain. The anterior pituitary gland is normally iso-intense with the rest of the brain. Adenomas are slow to take up Gd compared with the surrounding normal pituitary tissue and, thus, appear as hypoenhancing lesions. Other less specific signs of a pituitary tumor include deviation of the pituitary stalk away from the side of the tumor and an asymmetrical increase in the vertical height of the gland. When interpreting this latter sign, it is important to remember that the normal pituitary gland is enlarged and may have a convex upper surface during adolescence, particularly in females. Despite the superior resolution of the sellar contents compared with CT, conventional T1 weighted MRI is still only able to detect approximately one third to one half of microadenomas. Newer MRI sequences offer the opportunity to improve the resolution between normal and abnormal tissue.

Prolactinomas

The prolactinoma is the most common pituitary adenoma in childhood and adolescence. It arises from acidophilic cells that are derived from the same lineage as the somatotropes and thyrotropes. PRL-secreting adenomas may also stain for and secrete GH and occasionally TSH. The majority of prolactinomas during the pediatric years occur in adolescence. The presentation of these tumors may vary, depending on the age and sex of the child. Prepubertal children typically present with a combination of headache, visual disturbance, and growth failure, whereas pubertal females frequently present with symptoms of pubertal arrest, hypogonadism ± galactorrhea due to suppression of gonadotropin secretion or because of local compression and destruction of the pituitary. Galactorrhea needs to be excluded by expressing the breast because teenagers may not spontaneously volunteer it as a symptom and it may not occur spontaneously. Pubertal males may present with headaches and visual impairment, as well as pubertal arrest or growth failure. Gynecomastia is not a common sign. Males are more likely than females to have a macroadenoma at presentation (13, 15, 16). This may be explained by the fact that gonadotropin release is sensitive to the effects of hyperprolactinemia, enabling earlier detection of the tumor (13, 15, 16).

The differential diagnosis of prolactinoma is secondary hyperprolactinemia, which may be caused by any disorder that mechanically (tumors and infiltrative disease of the pituitary, infundibulum, hypothalamus), neurogenically (nipple stimulation, chest wall lesions, physical or emotional stress), or pharmacologically (e.g. phenothiazines, metoclopramide, centrally acting antihypertensives) leads to loss of dopaminergic suppression of the pituitary lactotropes.

Given the diverse presentations of prolactinoma, the threshold for measuring PRL levels should be low. There is some overlap between PRL levels seen with microadenomas and those of secondary hyperprolactinemia. Random PRL measurements that are modestly elevated should, therefore, be repeated, fasting an hour after placement of an indwelling cannula. If there is significant elevation or if modest elevation persists, then this warrants further investigation. In the presence of secondary hypogonadism and after excluding reversible factors that may cause hyperprolactinemia, treatment should be started.

Unless there is an acute threat to vision, hydrocephalus, cerebrospinal fluid leak or other surgical emergency, medical management with dopamine agonists should be attempted first before surgical treatment is considered. Bromocriptine was one of the original dopamine agonists used to treat prolactinoma. It is effective in causing tumor shrinkage and controlling PRL levels in small tumors, although the results in larger tumors are variable. The main disadvantage of bromocriptine is the common side effects of gastrointestinal disturbance and postural hypotension. Pergolide is at least as efficacious as bromocriptine at producing reduction in tumor size and normalization of PRL levels with the advantage of once daily dosing and reduced cost. Pergolide has a similar frequency and profile of side effects as bromocriptine. Newer ergot-dopamine agonists such as cabergoline can be given once or twice weekly, have fewer side effects, and seem equally, if not more efficacious, at controlling PRL levels and producing tumor shrinkage than pergolide and bromocriptine. Cost is their main drawback.

Corticotropinomas

Beyond the first 5 yr of life, ACTH-secreting adenomas account for 80–90% of children who develop Cushing’s syndrome. The classic presentation is one of rapid weight gain with striae, hypertension, growth failure, and pubertal failure or arrest, with hirsutism and premature pubarche in prepubertal children. Insulin resistance is common, although frank diabetes occurs infrequently. Skin thinning and easy bruising are uncommon, proximal myopathy is less common, and neuropsychiatric symptoms differ from adult patients. Instead of depression, memory problems, and sleep disturbance, children with Cushing’s syndrome frequently tend to be obsessive and are high performers at school (unpublished data).

The differential diagnosis includes primary adrenal tumors (more frequently seen in first 3 yr of life), ectopic ACTH production (bronchial or thymic carcinoids), and, very rarely, ectopic or eutopic CRH-producing tumors. Pseudo-Cushing’s syndrome is almost never seen in children and younger adolescents.

The first aim of assessment involves confirmation of Cushing’s syndrome. Several 24-h urine free cortisol (UFC) measurements should be obtained. UFC values should be corrected for the child’s body surface area (most normal ranges are per 1.73 m2) and interpreted in the light of the normal range of each laboratory. Additional evidence for Cushing’s syndrome includes failure of the serum cortisol to suppress to less than 3 µg/dL the morning after receiving 15 µg/kg (low dose) of dexamethasone at midnight.

Once the diagnosis of Cushing’s syndrome is established, it is then necessary to establish that the Cushing’s syndrome is due to an ACTH-secreting pituitary adenoma. Biochemical support for this includes stimulation of ACTH and cortisol following injection of ovine-CRH (oCRH; 1 µg/kg iv) and suppression of cortisol by more than 50% after 120 µg/kg of dexamethasone given at midnight (high dose). The latter test has a sensitivity that is comparable with the 85% of the formal Liddle test while having the advantages of being inexpensive, able to be done as an outpatient, and not requiring timed urine collections.

If the pituitary MRI is negative and other investigations indicate ACTH dependence, then oCRH-stimulated bilateral inferior petrosal sinus sampling can be used to confirm that the ACTH is coming from the pituitary gland and can also assist in lateralizing the tumor with approximately 75% accuracy. ACTH levels are simultaneously measured from both central and peripheral sites before and after injection of oCRH (17). The sensitivity of this test at confirming pituitary ACTH dependence is 97%. Other investigators have tried to improve sensitivity of the test and avoid the need for CRH by sampling both cavernous sinuses. Although early studies did not find this useful (18), a recent study suggested that this technique might be superior to inferior petrosal-sinus sampling (19).

Surgical excision is the treatment of choice for ACTH-secreting adenomas, the majority of which are small at diagnosis. The cure rate is significantly greater in those patients who have noninvasive microadenomas and is successful in over 90% of the cases, with a recurrence rate of less than 10%. Even in patients with large tumors or tumors invading the cavernous sinuses, there is still a good chance of cure with surgery alone, although the recurrence rate in these circumstances is significantly greater. When surgery is successful, patients become hypocortisolemic and usually require hydrocortisone supplementation (8–10 mg/m2·day given in the morning and education about stress dosing) for 6–12 months after surgery. Withdrawal of supplementation should be based on confirmation of a cortisol response of more than 18 µg/dL, 30 min after stimulation with 250 µg Cortrosyn.

If the tumor is surgically unresectable, or after a second recurrence, radiotherapy will produce normalization of cortisol in the majority of patients, although delayed plurihormonal hormone deficiency is expected. The time taken to normalize ACTH levels after radiotherapy is dependent on the size of the tumor and the dose of radiotherapy used. Medical adrenal blockade with ketoconazole (10–15 mg/kg·day, monitoring liver function tests) is commonly needed. Fractionated radiation doses of 35–50 cGy have a 2-yr cure rate of approximately 70–80% of children (20).

Somatotropinomas

GH excess may arise as the result of a somatotropinoma or from somatotrope hyperplasia. GH-secreting adenomas account for 5–15% of pediatric pituitary tumors (10, 13, 14, 21). Hyperplasia arises from either genetic mutations that result in constitutive activation of the somatotrope and stimulate its division (McCune Albright syndrome, MEN-1, and the Carney complex) or rarely from hypothalamic or ectopic tumors that secrete GHRH. Somatotropes are believed to have the same ancestral lineage as the lactotropes and thyrotropes. Consequently, tumors of this lineage may stain for and secrete any or all of these hormones, although immunopositivity for a particular glycoprotein hormone does not necessarily imply that the tumor secretes this hormone in clinically significant amounts.

The presentation of GH excess in children differs, depending on whether the epiphyseal growth plate is open. Before epiphyseal fusion, accelerated growth velocity is prominent. As epiphyseal fusion approaches, the spectrum of symptoms becomes more like that seen in adult patients (glucose intolerance, acral and facial changes, sweating, nausea). Unlike adults, there have been no reports of a significant increase in colonic polyposis or malignancy or thyroid nodules. Somatotropinomas are commonly macroadenomas at presentation and, thus, may cause headaches and visual disturbances in addition to the above endocrine and metabolic symptoms.

Biochemical evaluation includes the demonstration of elevated insulin-like growth factor I (IGF-1; overlap exists with IGF-1 levels seen during normal puberty and pregnancy) and random GH levels. Further biochemical evaluation should include an oral glucose tolerance test with failure of GH suppression or a paradoxical rise in GH after an oral glucose load of 1.75 g/kg considered positive responses, although this test alone may result in an unacceptably high false positive rate (22). GH-secreting cells from patients with somatotrope hyperplasia or somatotrope adenomas frequently also express TRH receptors on their surface; thus, GH secretion by the tumor may be stimulated by administering TRH. This latter test is used for the diagnosis and monitoring of somatotropinomas.

Surgery has traditionally been the first line of treatment for acromegaly, with radiation reserved for cases that were not surgically curable. Dopamine agonists have been used, but the high doses required to achieve adequate GH suppression frequently produce unacceptable side effects and with normalization of IGF-1 levels reported in only 10% of patients and tumor shrinkage in fewer than 20% of patients (23). The results with dopamine agonists may be better in tumors that cosecrete PRL and GH. Somatostatin analogs have been used in the treatment of acromegaly in adults since the mid 1980s. Long-term trials of octreotide in adults with acromegaly resulted in suppression of GH to less than 5 µg/L in 65% and less than 2 µg/L in 40%, with normalization of IGF-I in 56% of those studied (24). Octreotide has been shown to result in a significant reduction in tumor size in up to 40% of patients, although this is not sustained after withdrawing treatment (25). The dose of octreotide required to suppress GH and produce tumor shrinkage is quite variable, with determinants including tumor size and the density of somatostatin receptor expression on tumor cells. The biggest deterrents to the use of octreotide have included price, the need for three daily sc injections and the occurrence of cholestasis and cholelithiasis. Lanreotide, is a recently approved long-acting, slow-release depot somatostatin analog. Trials demonstrate that it provides effective suppression of GH and IGF-I levels, although over 3 yr significant tumor shrinkage occurred in only 15% of patients (26).

With the development of improved GH assays, the definition of cure of GH-secreting tumors has become increasingly rigorous, from an initial definition of an unsuppressed GH value of less than 10 µg/dL to the current definition that requires a return of the IGF-I levels to normal, with glucose-induced suppression of GH to less than 1 µg/dL (immuno-radiometric assay).

Thyrotropinomas

Thyrotropinomas are rare in adult patients and rarer still during childhood and adolescence with only a few cases having been reported. They are frequently macroadenomas at diagnosis presenting with headache, visual disturbance, and variable symptoms and signs of hyperthyroidism. A significant number of patients undergo medical or surgical thyroid ablation before the diagnosis is established. Biochemical features include elevation of free T4 and T3, but lack of TSH suppression. The differential diagnosis is isolated central thyroid hormone resistance. Biochemical distinction between adenomas and central T4 resistance can be made by lack of response to TRH stimulation (sensitivity 71%, specificity 96%), elevation of {alpha}-glycoprotein subunit (sensitivity 75%, specificity 90%) and elevated ratio of {alpha}-subunit to TSH (83% sensitivity, 63% specificity) in adenomas (27) (Table 1Go).

Transsphenoidal surgery is the treatment of choice for these tumors, although they are frequently large and invasive and require adjunctive radiation therapy. Medical suppression of thyroid hormone synthesis may result in increased tumor growth. Studies have shown that treatment with octreotide can normalize thyroid hormone levels in 80–90% and produce tumor shrinkage in up to 50% of cases and is of use when surgery is not possible or when there is residual or recurrent tumor (27, 28, 29).

Hormonally inactive pituitary adenomas

Hormonally inactive adenomas account for 33–50% of pituitary tumors in some adult series, but represent only 4–6% of cases in the pediatric literature (13, 21). These tumors are believed to arise from gonadotrope cells and are frequently macroadenomas at diagnosis, presenting with growth and/or pubertal failure or with headaches and visual disturbance. They may have discordant secretion of the {alpha}-glycoprotein hormone subunit with one or more of the ß-glycoprotein hormone subunits and chromogranin A.

Surgery is the main means of treatment. Management of these tumors in adult patients involves observation of small tumors and surgical debulking of symptomatic tumors. Due to the relative rarity of nonfunctioning pituitary tumors in children and the difficulty distinguishing them from craniopharyngiomas, it is likely that all of them will be surgically treated.


    Advances in the Imaging and Treatment of Pituitary Tumors
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 
Although CT was a major advance in central nervous system imaging, it provided suboptimal images of the pituitary and parasellar region due to its limited soft tissue contrast. Large tumors in the pituitary region were readily visualized, but smaller intrasellar tumors remained difficult to see. MRI provided much clearer images of the pituitary and hypothalamic area and had the ability of depicting anatomy in all three planes. The spacial resolution of the MRI is such that enables the observer to identify adenomas in the range of 4 mm. Attempts to improve this resolution further were unsuccessful, with a significant increase in the incidence of false positive results due to the phenomenon of signal averaging and increased background "noise." There is preliminary evidence that different methods of MRI signal acquisition may allow thinner slices and provide images that have improved inherent tissue contrast between normal and abnormal tissue without significantly increasing the false positive rate.

Intraoperative ultrasound during transsphenoidal surgery has been shown to be valuable in tumor localization in patients with Cushing’s disease (30). This technique provides good visualization of the interface between tumor and normal pituitary and has the potential to reduce operative morbidity by reducing the extent of surgical exploration needed and identifying sellar and parasellar structures that may be damaged.

Positron emission tomography with fluorodeoxyglucose has significant promise, particularly in postoperative patients, for distinguishing tumor recurrence from surgical scarring. Positron emission tomography scanning relies on the principle that neoplastic cells are more metabolically active than normal tissue so have an increased affinity for glucose. By radiolabeling glucose with 18F, tumors can be visualized due to their focal increase in glucose uptake.

Another technique that has become available in the last 10 yr and has been applied to pituitary tumors is the use of radiolabeled receptor ligands that are known in vitro to be expressed by pituitary tumors. 111In-diethylenetriamine pentaacetic acid-labeled-octreotide is an example of this technology. It was hoped that tumor uptake would both localize the tumor and might also predict subsequent tumor responsiveness to octreotide. Results have been disappointing, with variable positivity and lack of correlation between scan positivity and response to octreotide (31, 32). Octreotide scanning has a more significant role in detecting ectopic tumors that secrete pituitary hormones or hypothalamic-releasing hormones (e.g. GHRH in cases of acromegaly and possibly ectopic ACTH production causing Cushing’s syndrome).

Receptor imaging has also been tried. The type 2 dopamine receptor is found on virtually all prolactinomas, some somatotropinomas, and nonfunctioning adenomas (31). It was hoped that this technique could be used for identifying tumors expressing this receptor and to predict response to dopaminergic agonists; however, this has not materialized as yet.

Combinations of transcranial surgery and radiotherapy were once the only options available for pituitary tumors. They both had an unacceptably high morbidity and mortality. The development of transsphenoidal surgery enabled safe excision of microadenomas and some minimally invasive macroadenomas without risk to the hypothalamic area, the optic nerves, or the circle of Willis. Endoscopic transsphenoidal surgery has been used in some centers, although the need to aspirate the tumor rather than enucleate it and the paucity of endocrine follow-up data mean that results should be regarded as preliminary. In large, hormonally active tumors, surgery, and/or medical treatment may not result in normalization of hormone levels, and radiation therapy may be necessary. Nonendocrine complications of radiotherapy have included up to 20-fold increase in second tumors within the radiation field, visual impairment and problems with memory. The use of multiportal fractionated irradiation of 30–50 Gy over a 5-week period has reduced these complications, however, it may still take several years to normalize hormone levels and is usually complicated by varying degrees of plurihormonal pituitary deficiency.

Advances in radiation techniques offer encouraging results. Radioactive cobalt-based gamma knife radiosurgery was first developed in the 1960s but has become a feasible treatment option in the last 10–15 yr with the advent of MRI for accurate planning and treatment (33). It uses up to 60 sources of stereotactically focused beams of Cobalt-60. Its advantages over conventional radiotherapy are that treatment is delivered in one single dose (25–30 Gy for secretory tumors and 20 Gy for nonfunctioning tumors) producing more rapid control of hypersecretion than conventional radiotherapy. Furthermore, due to focusing, gamma knife radiosurgery significantly reduces the scatter and potential damage to adjacent structures. Its greatest role is in treating residual tumor that cannot be safely removed surgically. The more recently developed linear acceleration-based radiosurgery may be as or more effective and safe than gamma knife radiosurgery and has been rapidly becoming more readily available (33).

Over the last few years, there have been major advances in the understanding of the genetics of pituitary embryogenesis and oncogenesis (34). In parallel with this improved understanding of tumor genetics has come the development of vectors that can introduce DNA into normal and neoplastic pituitary cells in vitro and in vivo. Once the mechanisms of pituitary oncogenesis are understood, this may open the door for the use of targeted controllable gene therapy for tumors that can not be adequately or safely managed using conventional treatments (35).


    Conclusion
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 
Pituitary neoplasms are rare in children and adolescents, with craniopharyngiomas being 10–20 times more frequent than adenomas. The most common presentation is with symptoms of headache and visual disturbance, although signs of growth failure and disturbances of pubertal development are frequently present. Unlike adult patients, nonfunctioning pituitary adenomas are rare in children and adolescents. With the exception of prolactinomas, once the tumor is identified transsphenoidal surgery is the treatment of choice. Adjunctive radiotherapy and specific hormonal therapies may be needed, particularly in large or invasive tumors where surgery alone is less likely to be curative. Advances in radiotherapy provide promise of reduced treatment-associated complications in patients with large or invasive tumors. The significant advances in the understanding of the genetics and natural history and in the diagnosis and treatment of these tumors will hopefully make it possible that one day surgery will no longer be necessary.


    Acknowledgments
 
We sincerely thank Dr. Nicholas Patronas, Chief (Neuroradiology Section, National Institutes of Health), for reviewing this manuscript and for his constructive comments.

Received September 15, 1999.

Accepted September 23, 1999.


    References
 Top
 Introduction
 Craniopharyngioma
 Pituitary Adenomas
 Advances in the Imaging...
 Conclusion
 References
 

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