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

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3. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
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