Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032
Address correspondence and requests for reprints to: Sharon L. Wardlaw, M.D., Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032. E-mail: sw22{at}columbia.edu
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Introduction |
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PRL-Secreting Pituitary Tumors |
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Patients with PRL-secreting microadenomas usually present with symptoms caused by the high PRL levels. Patients with PRL-secreting macroadenomas, however, often present with additional symptoms related to the presence of a pituitary mass lesion. The treatment of patients with prolactinomas varies with the symptoms of the patient and the size of the tumor (2). Hyperprolactinemia causes hypogonadotropic hypogonadism in women and men, primarily due to the inhibitory effect of high PRL levels on hypothalamic GnRH release. The most common symptoms of hyperprolactinemia are amenorrhea and galactorrhea in women and decreased libido and impotence in men. Treatment is clearly indicated to restore fertility and to reverse symptomatic hypogonadism. The long-term effects of hypogonadism on bone mineral density and the cardiovascular system also need to be considered. A major therapeutic objective is also to reduce the size of the tumor and to limit future growth. Reduction in tumor size is of primary importance in patients with large macroadenomas and symptoms of a mass lesion, including visual symptoms secondary to compression of the optic chiasm, cranial neuropathies, and hypopituitarism. This is not the case with microadenomas. Several studies now support the view that in the majority of patients, untreated microadenomas do not grow into macroadenomas (2, 3). Thus, the presence of a small tumor per se (in the absence of clinical symptoms) is not a definite indication for surgical intervention or for medical intervention. These patients must, however, continue to be carefully monitored. The presence of a macroadenoma, however, even without symptoms, usually warrants treatment to prevent future growth.
Medical treatment with long-acting dopamine agonists is very effective
in reducing PRL levels and restoring gonadal function in patients with
prolactinomas. In addition, these drugs cause significant tumor
shrinkage in 75% of patients (2, 4). In some patients with large
invasive tumors, the shrinkage can be dramatic. Changes in visual
fields can be noted within days after initiating therapy. However, if
the dopamine agonist is stopped, hyperprolactinemia usually recurs as
well as reexpansion of the tumor. Transsphenoidal surgery by an
experienced pituitary neurosurgeon is also very effective in curing
7090% of patients with PRL-secreting microadenomas (4, 5, 6, 7). Initial
enthusiasm for transsphenoidal surgery of PRL-secreting microadenomas
has, however, been dampened considerably by high recurrence rates
(1750%) as well as by the effectiveness of current medical therapy
with long-acting dopamine agonists (6, 7). Surgical cure rates are much
lower for macroadenomas. Transsphenoidal surgery, however, continues to
be used and is effective if dopamine agonists are not tolerated or if
they do not work. Surgery may also be indicated for large tumors with
PRL levels in the range seen with pituitary stalk compression, raising
the suspicion that the lesion may be something other than a
prolactinoma. Very rarely, radiotherapy may be required depending on
the response to surgery and dopamine agonist treatment.
The majority of patients with PRL-secreting tumors who require therapy can be safely and effectively treated with dopamine agonists. Bromocriptine and pergolide are the two long-acting dopamine agonists that have been available for use in the United States for many years. Recently, another very long-acting dopamine agonist, cabergoline, has become available in the United States. All three drugs are ergoline derivatives. Pergolide is only approved in the United States for the treatment of Parkinsons disease, but it has been shown to be an extremely safe and effective treatment for prolactinomas (8, 9). In a large, randomized, controlled multicenter trial, pergolide and bromocriptine were shown to be equally effective in lowering PRL levels and causing tumor shrinkage (9). The advantages to the use of pergolide compared with bromocriptine are that it is much more potent, is longer-acting, and is considerably cheaper. Thus, pergolide can usually be administered in one dose of 0.050.1 mg at night. Bromocriptine (2.5 mg) is usually administered two to three times a day. Cabergoline is even longer-acting than pergolide and can be administered at doses of 0.51 mg once or twice weekly. Like bromocriptine and pergolide, it is very effective in normalizing PRL levels, restoring gonadal function, and in causing tumor shrinkage. Cabergoline was shown to be better tolerated than bromocriptine in a large double-blind comparison of the two drugs (10). In that study, 3% of patients discontinued cabergoline because of drug intolerance as compared with 12% of patients on bromocriptine. In addition, prolactinomas resistant to other dopamine agonists have been shown to respond to cabergoline (11, 12). In a recent large retrospective study of 452 patients with pathological hyperprolactinemia, most of whom had pituitary tumors, cabergoline was shown to be effective in many patients who were previously bromocriptine intolerant or resistant (13).
Our current practice is to treat most patients who do not wish to become pregnant with cabergoline. Women who wish to become pregnant are still treated initially with bromocriptine because of the extensive safety record with bromocriptine for this purpose. A growing number of women, however, have become pregnant while taking cabergoline and have delivered healthy children, but the numbers are still relatively small. It is anticipated that in the future cabergoline may be recommended as the drug of choice for this purpose as safety data accumulates. Once pregnancy is confirmed, bromocriptine is usually stopped. Women with microadenomas are very unlikely (<5%) to experience problems with clinically significant tumor growth during pregnancy (14). With macroadenomas, however, it is more likely (1535%) that the tumor will re-expand after bromocriptine withdrawal and may enlarge further, causing compressive symptoms with continued estrogen stimulation during the course of pregnancy. If the patient becomes symptomatic, bromocriptine can be restarted or surgery can be considered. In all patients, when initiating therapy with any of the dopamine agonist drugs, it is important to start with a very small dose to minimize side effects. The most common side effects are nausea, vomiting, and postural hypotension. These side effects usually disappear with continued treatment. With bromocriptine and pergolide it is our practice to begin with a quarter to half tablet once a day with a snack at bedtime. The dose is then gradually increased as tolerated by the patient to 2.5 mg po twice or three times a day for bromocriptine and 0.050.1 mg po daily for pergolide. Cabergoline is started at a dose of 0.25 mg po once a week and gradually increased to 0.5 mg once or twice a week. A serum PRL level is checked after 1 and 2 months, and, if necessary, the dose can be increased.
Dopamine agonists should be considered the first line of therapy, even with very large invasive PRL-secreting tumors that are causing compressive symptoms. Medical therapy often causes dramatic tumor shrinkage in these patients, and the vast majority never require surgery. If vision is compromised, visual acuity and visual fields should be carefully monitored. PRL levels should also be measured, and the dose of dopamine agonist should be adjusted accordingly. In general, if the PRL level does not fall, it is unlikely that there will be significant tumor shrinkage. A fall in PRL, however, is not always accompanied by tumor shrinkage. It is, therefore, important to document tumor shrinkage by repeating a MRI in 36 months or sooner if vision is impaired and does not improve. In many patients, visual abnormalities may improve rapidly as the tumor shrinks. In some patients with long-standing visual deficits, however, vision may not improve despite tumor shrinkage and decompression of the optic chiasm. In these patients it is unlikely that vision will improve with subsequent surgery. If the optic chiasm is not adequately decompressed, however, surgery may be indicated to restore vision. The majority of patients with large prolactinomas, however, can be adequately treated with dopamine agonists and never require surgery. Once PRL levels fall and there has been significant tumor shrinkage, it is very unlikely that the patient will become resistant to drug therapy. It is not uncommon for the maintenance dopamine agonist dose to be reduced during long-term treatment.
Because the natural history of untreated PRL-secreting microadenomas is quite benign, indications for treatment depend on the patients symptoms. Dopamine agonist treatment will correct the hypogonadism and restore fertility in most cases. Alternatively, estrogen replacement therapy can be used to treat symptoms of estrogen deficiency and to prevent the long-term complications of estrogen deficiency. Oral contraceptives can be used to treat younger women who desire contraception. Treatment with estrogen without concurrent treatment with dopamine agonists seems to be safe and not to be associated with significant tumor growth in most cases (15). Patients should be followed regularly, however, and PRL levels should be measured because there is a small risk that estrogen could stimulate tumor growth. If tumor growth is noted while taking estrogen, therapy with a dopamine agonist should be initiated.
In summary, the majority of patients with PRL-secreting microadenomas and macroadenomas can be effectively treated with dopamine agonists. Transsphenoidal surgery is also an effective option for patients who are resistant to or intolerant of these drugs.
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GH-Secreting Pituitary Tumors |
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The goals of therapy for acromegaly are to both normalize the excess secretion of growth hormone and IGF-I, thereby alleviating the associated symptoms and to surgically remove or debulk large tumors to prevent damage to parasellar structures. Long-term excess GH secretion in acromegaly is associated with a 2-fold greater mortality rate than in the general population and an increased morbidity due to the cardiovascular, pulmonary (airway obstruction and sleep apnea), and malignant complications of this disease (17). Recent evidence suggests that the increased mortality rate associated with persistent active disease can be reduced to normal with therapy that significantly reduces the GH and IGF-I levels (18, 19, 20, 21). Therefore, the goal of therapy should be to achieve adequate biochemical remission as documented by both a normal age-adjusted IGF-I level and by a nadir GH level after oral glucose of less than 1.0 ng/mL by a sensitive GH assay (22).
Transsphenoidal surgery, with success in many patients and very low
morbidity, is generally accepted to be the initial mode of therapy for
most patients with acromegaly. In recent series from experienced
pituitary surgeons, 90% of microadenomas and half of macroadenomas
will achieve biochemical remission based on normalization of IGF-I
levels after transsphenoidal surgery alone (21, 23). Nearly two thirds
of noninvasive macroadenomas can be cured surgically (23). The
recurrence rate after strictly defined biochemical cure is quite low at
less than 6% (21, 23). Complications after transsphenoidal surgery
occur in less than 7% of cases and include diabetes insipidus,
syndrome of inappropriate secretion of antidiuretic hormone, and
rarely cerebrospinal fluid leaks or meningitis (23). For those
patients who do not achieve biochemical remission after transsphenoidal
surgery, currently available therapeutic options include medical
therapy with dopamine agonists and/or somatostatin analogs and
radiation therapy.
Recent data suggest that radiotherapy may not be as effective in curing acromegaly as previously thought if normalization of IGF-I values is used to define cure. Several recent series have reported that despite a reduction in GH levels in most patients, from only 542% of patients will achieve normalization of their IGF-I level after radiotherapy (21, 24, 25). Long-term follow-up comparing various modalities such as gamma knife therapy, proton beam, and focused conventional RT are needed before full assessment of their comparative efficacy can be made. Currently, with the availability of effective medical therapies and the drawbacks of radiotherapy [i.e., the long lag time to therapeutic effect and high incidence (up to 50%) of hypopituitarism with time,] we usually reserve radiotherapy for large or invasive macroadenomas that could not be removed completely surgically or for patients resistant to medical therapy.
Medical therapy has assumed a more prominent role in the treatment of acromegaly as the numbers and efficacy of the therapies available have increased. The two classes of medication currently available in the United States for therapy of acromegaly are dopamine agonists and somatostatin analogs. Although many acromegalics treated with the dopamine agonist bromocriptine will have some amelioration in symptoms, only 20% of patients will achieve a GH less than 5 ng/mL and IGF-I level will normalize in only 10% (26). Bromocriptine is often required in large doses (up to 20 mg/day), and side effects are common. Cabergoline, the new more potent dopamine agonist, approved in the United States for use in PRL-secreting tumors, holds promise for improved efficacy and tolerability over bromocriptine for the treatment of acromegaly. In a recent study, in 64 patients with acromegaly treated with cabergoline at doses ranging from 1.01.75 mg/week for up to a 40-month period (27), IGF-I levels normalized in 39% of patients and fell to 300450 µg/L in another 28% (27). Higher basal IGF-I or GH levels were associated with a reduced efficacy. As expected, tumors that cosecrete PRL are more likely to be responsive to cabergoline therapy. As with other dopamine agonists, the most frequent side effects are nausea, constipation, headache, and dizziness; but in comparative studies with bromocriptine in patients with prolactinomas the side effects have been somewhat less with cabergoline (10). In patients with persistent mild to moderate disease after surgery, and who are minimally symptomatic, a trial of a dopamine agonist such as cabergoline should be considered. Cabergoline is begun at a dose of 0.25 mg/week and can be increased as tolerated up to 3.0 mg/week as needed to normalize IGF-I levels.
The most effective medical therapies for acromegaly currently available are the somatostatin analogs. Two forms of the somatostatin analog octreotide are now available in the United States for treatment of acromegaly, a shorter-acting form and a long-acting depot form. The shorter-acting form of octreotide is given as three sc injections daily of 100250 µg each. Octreotide also can be infused sc via a pump with a reportedly somewhat greater efficacy (28). Doses over 800 µg/day are generally not felt to increase effectiveness (17). The long-acting depot formulation recently released in the United States, Sandostatin LAR Depot (Novartis Pharmaceuticals, East Hanover, NJ), is administered as a monthly im injection in doses ranging from 10 mg to 30 mg (20 mg/month is the recommended starting dose). For patients new to these medications, an initial 2-week trial of the sc formulation of octreotide should be administered to ensure drug tolerability before the first depot injection.
Overall, clinical trials have shown similar control of GH and IGF-I
levels in patients switched from the sc form to the depot form of
octreotide. Normalization of IGF-I levels can be expected to occur in
64% of patients treated with sc octreotide for up to 3 yr (29), and up
to 67% of patients will achieve normalization of IGF-I levels with the
depot formulation (30, 31). Although only a small percentage of
patients who responded sub-optimally to the sc octreotide had a more
favorable response to the depot formation in clinical trials, the
improved compliance expected with the depot form may result in a
greater observed efficacy in clinical practice with this formulation.
Although GH and IGF-I levels do not normalize in up to one third of
patients treated with octreotide, symptomatic relief can be expected in
most (29), and headache, in particular, is relieved in up to 95% of
patients. Recent evidence of improved cardiac functional status with
octreotide treatment supports the belief that effective medical therapy
may impact on morbidity and mortality in acromegaly (32). One drawback
to the use of these medications alone in some patients with acromegaly
is that long-term data on tumor shrinkage with their use is scant.
Overall, only 40% of patients treated with octreotide demonstrate a
significant decrease in tumor size (33). Tumor shrinkage data with the
depot formulation is available in only a very small number of
patients.
Both medications are not infrequently associated with abdominal discomfort, loose stools, nausea and mild malabsorption, which in most patients subside with continued use. Although up to 26% of patients will develop new gallstones during somatostatin analog therapy, they remain asymptomatic in the majority of patients and should be managed as would gallstones in nonacromegalic patients (33). In asymptomatic patients, routine gallbladder sonogram during therapy, therefore, is not felt to be necessary (33). Other less frequent side effects include asymptomatic bradycardia, abnormalities of thyroid function, transient hair loss and vitamin B12 deficiency, and also pain at the site of injection in a small percentage of patients receiving the depot formulation (30, 31). Concurrent somatostatin analog and dopamine agonist therapy may also provide additional benefit (34).
The longer-acting depot form of octreotide, because of ease of administration, likely will be chosen as the adjuvant therapy of choice in most patients who fail surgery for acromegaly. The shorter-acting formulation may be preferred in certain situations, such as for preoperative treatment in patients with signs of upper airway compromise or significant cardiovascular disease to attempt to rapidly lower GH levels and possibly reduce perioperative complications (35). In selected cases in which the chance of surgical cure is low or in whom surgery is contraindicated, the somatostatin analogs have been suggested as first line therapy for acromegaly (33, 36). Long-term follow-up of such patients will be needed to compare their outcome, with respect to tumor size in particular, with similar patients receiving transsphenoidal surgery.
In the near future, analogs of GH that act at the GH receptor as antagonists may also enter the armamentarium of drugs available for the treatment of acromegaly. Early data from clinical trials with a GH antagonist, pegvisomant (B2036-PEG), demonstrate that this medication is well tolerated and in sufficient doses normalizes IGF-I levels in nearly all patients with acromegaly, including those resistant to somatostatin analogs (37).
In summary, transsphenoidal surgery is the primary treatment of choice in the majority of patients with acromegaly. The role of primary medical therapy with somatostatin analogs in patients unlikely to be cured surgically is yet to be determined. For those patients with persistent elevation of GH or IGF-I levels after surgery, medical therapy should be undertaken. For those patients with mild disease, a trial of the oral dopamine agonist cabergoline can be initiated. If this fails or in patients with moderate to severe disease, therapy with a somatostatin analog should be begun. In the near future, the GH antagonist pegvisomant may also be another option for medical therapy. Radiotherapy, in conjunction with appropriate medical therapy, should be considered for patients with significant residual tumor after surgery or in whom medical therapy is unsuccessful.
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ACTH-Secreting Pituitary Tumors |
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Transsphenoidal surgery is currently the treatment of choice for patients with Cushings disease. Microadenomas are usually found in most patients at the time of surgery and can be selectively removed with eventual resumption of normal hypothalamic-pituitary-adrenal function. If no adenoma is found, a partial hypophysectomy guided by the petrosal sinus ACTH levels may be elected. At times, in an older patient in whom fertility is not an issue, a near total hypophysectomy may be elected because of the morbidity and mortality associated with this disease. In several large series of patients undergoing transsphenoidal surgery for Cushings disease, cure rates of 8090% have been reported for tumors confined to the sella (43, 44). Most patients have been cured by selective adenomectomy, but a small number have been cured by total hypophysectomy if no tumor was identified at surgery. In a large series reported by Mampalam et al. (43), there was an overall remission rate of 76% in 216 patients after transsphenoidal surgery. In that series, 9 of 164 patients had recurrence of disease. The disease recurred at an average of 3.8 yr after surgery.
Postoperatively, if the patient has been cured, there will be transient hypoadrenalism until the normal hypothalamic-pituitary-adrenal axis recovers. If hypocortisolism is not demonstrable after surgery, it is unlikely that the patient is cured. The best long-term prognosis for cure is seen in patients with plasma cortisol levels of less than 1µg/dL who require prolonged glucocorticoid replacement (45). After successful transsphenoidal surgery, patients will typically require daily glucocorticoid replacement for 312 months (46). Cured patients often complain of steroid withdrawal symptoms, including myalgias and arthralgias, despite physiological glucocorticoid replacement. Physicians should be aware that previous psychopathology may persist into the postoperative period and new psychopathology may emerge. In one series, 66% of patients with Cushings syndrome had significant psychopathology, with a predominant diagnosis of atypical depression; after the correction of hypercortisolism, overall psychopathology decreased but the frequency of suicidal ideation and panic increased (47).
If the patient is not cured by surgery, options include a repeat transsphenoidal procedure, radiotherapy or, rarely, bilateral adrenalectomy. Depending on the extent of the first surgical procedure, a second more extensive hypophysectomy may be performed. Pituitary radiotherapy should then be considered as the next most appropriate treatment for patients not cured by transsphenoidal surgery. Although conventional pituitary irradiation has been successful in curing childhood Cushings disease, much lower cure rates have been reported in adults when used as primary therapy. Pituitary irradiation has, however, recently been shown to be an effective treatment in patients who have had transsphenoidal surgery but were not cured (48). In that series, 83% of patients had remissions after radiotherapy. The remissions began 660 months after radiation therapy, but in most cases remission occurred within 2 yr of treatment. The only side effect noted in this series was the development of variable degrees of hypopituitarism in 15 of 30 patients. Newer forms of stereotactic radiotherapy (a computer-assisted linear accelerator or cobalt-60, the gamma knife) may prove to be very effective, but long-term follow-up with these techniques for treating pituitary tumors is limited. Medical therapy is usually required to lower cortisol levels while waiting for the radiotherapy to take effect.
Medical therapy for Cushings disease is aimed primarily at the
adrenal and consists of several inhibitors of adrenal steroidogenesis
(49). Ketoconazole, an imidazole derivative that inhibits cortisol
synthesis at multiple steps, has been shown to rapidly suppress
cortisol levels in patients with Cushings disease (49, 50, 51).
Ketoconazole inhibits cholesterol side-chain cleavage,
11ß-hydroxylase, and 17-hydroxylase; inhibition of the 17, 20
lyase also affects androgen synthesis. The initial oral dose is usually
200 mg administered every 12 h, but doses of up to 1200 mg/day may
be required. The major side effects are alterations in hepatic function
and gastrointestinal symptoms. Liver function tests should be monitored
during therapy. At high doses ketoconazole may impair testicular
function. If ketoconazole is not effective or well tolerated, other
adrenal enzyme inhibitors including metyrapone, aminoglutethimide, and
o,pDDD (mitotane) can be used. Lower doses of several drugs can be
used in combination to minimize side effects. Etomidate, an imidazole
derivative related to ketoconazole, has been used iv to lower cortisol
levels in patients who cannot take oral medications (52). Mifepristone,
a glucocorticoid receptor antagonist, has been used in a small number
of patients, but it is difficult to monitor its effectiveness other
than by the clinical response because cortisol levels will not fall and
may actually increase. Medical therapy is not considered primary
therapy for established Cushings disease, but is often used in
conjunction with radiotherapy or preoperatively in a very debilitated
patient to improve the patients clinical condition before
surgery.
Bilateral adrenalectomy, which was the standard treatment in the past, is occasionally still used in patients who fail surgery and radiotherapy, but life-long treatment with glucocorticoid and mineralocorticoid will be required. In addition, patients are at risk for Nelsons syndrome manifested by a progressive increase in skin pigmentation due to an increase in ACTH levels and pituitary tumor growth. The risk is reduced, however, by prior pituitary radiotherapy.
In summary, the majority of patients with Cushings disease can be cured by transsphenoidal surgery with selective adenomectomy with subsequent recovery of normal hypothalamic-pituitary-adrenal function. Patients will require glucocorticoid replacement and careful monitoring during the period of transient adrenal insufficiency that occurs before the hypothalamic-pituitary-adrenal axis recovers. If surgery fails, a more extensive surgical procedure and/or radiotherapy is indicated. Medical therapy with ketoconazole and other adrenal enzyme inhibitors can be used as adjunctive therapy to lower cortisol levels.
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Glycoprotein Hormone (TSH, LH, FSH)-Secreting and Nonfunctioning Pituitary Tumors |
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FSH- and LH-secreting tumors that present with clinical symptoms of
hormone hypersecretion are very rare (55). Thus, the majority of
gonadotroph-producing tumors are clinically hormonally silent.
Pituitary tumors that present without clinical and biochemical evidence
of pituitary hormone hypersecretion are termed clinically
nonfunctioning adenomas and are in the majority of cases of gonadotroph
origin. Although clinically silent, in vitro evidence
demonstrates that most of these tumors do synthesize glycoprotein
hormones or their subunits, including FSH, free or ß subunits,
and, less commonly, LH (55). Serum gonadotropin concentrations are
usually normal, but elevations of serum-free ß-FSH or
-subunit may
be detected in some patients (56). Some have found elevation of serum
-subunit to be a useful marker (57), as well as an increase in
gonadotropin or subunit levels after TRH stimulation (58).
Nonfunctioning tumors, usually macroadenomas, typically come to medical attention because of visual disturbance, symptoms of hypopituitarism, or headache (59, 60). These tumors need to be distinguished from other sellar/parasellar masses that can mimic a pituitary adenoma (16). The major considerations in the differential diagnosis of pituitary adenomas are cysts, craniopharyngiomas, meningiomas, metastatic tumors to the pituitary, granulomatous and infiltrative processes, and lymphocytic hypophysitis. Diabetes insipidus is very uncommon at presentation in pituitary adenomas and should prompt consideration of a nonpituitary lesion. Although certain clinical and radiographic features may help in the diagnosis of nonpituitary lesions, some will not be diagnosed until the time of surgery (16). Nonfunctioning tumors may be accompanied by modest hyperprolactinemia, usually less than 100 ng/mL, due to compression of the pituitary stalk.
The initial management of nonfunctioning pituitary macroadenomas is transsphenoidal surgery with the goals being removal of tumor mass and decompression of parasellar structures. Transsphenoidal surgery has a low morbidity, results in improvement in visual loss in many cases (59), and may lead to recovery of pituitary function. Because of the large size and parasellar extension found in many of these tumors, they often cannot be completely resected. Even after apparent resection, recurrence rates after surgery may be as high as 16% (59). Postoperative radiotherapy is an option for treatment of residual tumor. However, clear prospective data on the benefits and outcome of radiotherapy for nonsecretory tumors are not available. The decision about whether to proceed to radiotherapy after surgery depends on the size of the residual tumor, the patients age, and the desire to retain pituitary function. Postoperative radiotherapy is clearly not necessary in every case. One may elect to follow with serial scans every 6 months, for the 1st yr, and then yearly thereafter to determine the rate of growth of the tumor and reconsider radiotherapy if there is tumor growth.
Attempts at medical therapy of nonfunctioning pituitary tumors with dopamine agonists and analogs of somatostatin have met with little success, in part because only a minority of these tumors bear dopamine or somatostatin receptors. In a few reported cases, bromocriptine therapy has decreased tumor size, but tumor shrinkage does not occur in most patients. Similarly, use of octreotide has been successful in improving vision in some patients with these tumors (56), but the response is very heterogeneous and its use should be reserved as with bromocriptine for patients unresponsive to other therapies.
Nonfunctioning pituitary tumors are not infrequently discovered on imaging studies done for unrelated reasons in patients without symptoms referable to the pituitary tumor. The management of these asymptomatic tumors or incidentalomas is somewhat controversial. Nonfunctioning microadenomas (<10 mm) need not be treated surgically and can be followed with serial MRI. Most agree, however, that surgery should be considered for asymptomatic macroadenomas. Depending on the size of the tumor and other medical conditions, however, one may elect to monitor the tumor on serial pituitary imaging studies and follow clinical signs and pituitary function. Little prospective data, however, is actually available on the natural history of asymptomatic pituitary tumors.
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Summary |
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Received July 28, 1999.
Revised September 17, 1999.
Accepted September 17, 1999.
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References |
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