Pituitary Adenomas: Current Methods of Diagnosis and Treatment

Drs. Buatti and Marcus concisely review the clinical presentation, diagnosis,and current management of pituitary adenomas. It would be difficult, ifnot impossible, for a brief review article to cover in depth all of theareas of controversy for such a broad subject. Consequently, several supplementarycomments are in order.

Medical Management

Drs. Buatti and Marcus do not elaborate very much on the successes ofmedical therapy for functional pituitary adenomas. Despite the drawbacksthey correctly point out, most endocrinologists presently choose dopamineagonist therapy (eg, bromocriptine [Parlodel], pergolide [Permax]) as thefirst line of therapy for prolactinomas.

A review of 271 patients with macroprolactinoma treated in 26 studiesfound that 79% of tumors shrink by 25% or more with dopaminergic treatment.[1,2]The amount of shrinkage increases over time, with approximately 86% oftumors decreasing by more than 50% after 1 year of therapy.[1] The advantagesof waiting for further shrinkage of a macroadenoma before performing surgerymust be weighed against the possibility that resection may become moredifficult after lengthy dopaminergic treatment.[1]

Medical control of acromegaly is less successful than that of prolactinomas,and therefore is usually not the primary therapy of choice. Bromocriptinelowers growth hormone levels in an average of 74% of patients but almostnever below 2.5 mcg/mL. Somatostatin analogs (octreotide [Sandostatin])decrease growth hormone levels in about 94% of patients, but, on average,only 21% achieve normalization of growth hormone.[3] Tumors shrink in anaverage of 35% of patients treated but usually by less than 50%.[3]

Medical therapy has also been tested in clinically nonfunctional pituitaryadenomas. Approximately 20% of these tumors shrink with bromocriptine therapy.[4]Medical therapy is therefore a reasonable option for patients with clinicallynonfunctional pituitary adenomas who have not responded to radiotherapyand who are poor candidates for surgical resection.

Surgical Resection

One recent surgical advance that deserves mention is the developmentof minimally invasive transnasal endoscopic techniques for pituitary surgery.[5,6]These procedures promise to reduce the morbidity of surgery to even lowerlevels than are achievable with transsphenoidal hypophysectomy. The majorityof patients can be discharged within 1 day after transnasal endoscopicsurgery.[5,6] The low morbidity of modern neurosurgical techniques weakensthe argument for skipping tissue diagnosis and proceeding with empiricradiotherapy in many patients with suspected pituitary adenoma.

Radiotherapy

Buatti and Marcus correctly state that radiotherapy to 45 Gy "canproduce cure in more than 90% of cases." This seems difficult to reconcilewith their statement that surgery is the treatment of choice, and may leadunfamiliar readers into thinking that radiotherapy is more effective thanit actually is. Although some centers have reported long-term control ratesof this magnitude with radiation therapy, other large series have reported20-year actuarial tumor control rates of only 72% to 76%.[7-9] The lowercure rates at these centers cannot be explained by differences in doseor technique.[7,8]

The use of radiation doses more than 45 Gy in 25 fractions for nonfunctionaltumors increases the risks of complications without improving tumor control.[7,8]Management of pituitary adenomas that progress after radiotherapy can beparticularly vexing.[8,10] Finally, even the most optimistic reports onfunctional pituitary adenomas require 15 years of follow-up before hormonenormalization rates reach 90%.[11] The morbidity and mortality of uncontrolledCushing's disease or acromegaly are too great to wait 10 to 15 years forhormone normalization after radiotherapy alone. For this reason, multimodalitytreatment is the norm for these tumors.

Radiosurgery and Stereotactic Radiotherapy

Radiosurgery and stereotactic radiotherapy are recent techniques thatshow a great deal of promise in the management of pituitary adenomas. Doseescalation (possible with optic pathway doses less than 8 Gy) can potentiallyincrease tumor control while improving the likelihood and speed of reachinghormone normalization for secretory tumors. Compared with conventionalfractionated radiotherapy, the ability of radiosurgery and stereotacticradiotherapy to treat smaller tumor volumes can potentially reduce thechances of hypopituitarism, second tumor development, and injury to thebrain or cranial nerves.

Since diagnostic imaging of pituitary tumors is not yet perfect, onepossible drawback of treating smaller image-defined tumor volumes is thesmall likelihood of missing an unseen area of tumor extension. Becauseof the long natural history of pituitary adenomas, long-term studies arestill needed to adequately assess the merits of radiosurgery and stereotacticradiotherapy relative to conventional radiotherapy and surgery.

Multidisciplinary Management

Pituitary adenomas are optimally managed by a multidisciplinary teamof neurosurgeons, endocrinologists, radiation oncologists, and other specialists.Cooperation among the team members is essential for applying new developmentsfrom clinical and laboratory research in diagnostic imaging, surgery, radiationoncology, pharmacology, pathology, and molecular biology to optimize carefor individual patients. Also, careful cost-effectiveness analyses areneeded to better define the merits of different therapeutic strategiesin these patients.

References:

1. Lamberts SWJ, MacLeod RM: Prolactinomas: Medical treatment, in LandoltAM, Vance ML, Reilly PL (eds): Pituitary Adenomas--Biology, Diagnosis andTreatment, pp 431-441. Edinburgh, Churchill Livingstone, 1996.

2. Bevan JS, Webster J, Burke CW, et al: Dopamine agonists and pituitarytumor shrinkage. Endocrin Rev 13:220-240, 1992.

3. Vance ML: Prolactinomas: medical treatment, in Landolt AM, VanceML, Reilly PL (eds): Pituitary Adenomas--Biology, Diagnosis and Treatment,pp 409-415. Edinburgh, Churchill Livingstone, 1996.

4. Liuzzi A, Zingrillo M, Ghiggi MR, et al: Clinically inactive adenomas:Medical treatment, in Landolt AM, Vance ML, Reilly PL (eds): PituitaryAdenomas--Biology, Diagnosis and Treatment, pp 409-415. Edinburgh, ChurchillLivingstone, 1996.

5. Jho HD, Carrau RL: Endoscopic endonasal transsphenoidal surgery:experience with 50 patients. Neurosurg Focus 1:10, 1996.

6. Jho HD, Carrau RL, Ko Y: Endoscopic pituitary surgery, in WilkinsRH, Renegarchary SS (eds): Neurosurgical Operative Atlas: American Associationof Neurological Surgeons, vol 5, pp 1-12. Park Ridge, Illinois, AmericanAssociation of Neurological Surgeons, 1996.

7. Flickinger JC, Nelson PB, Martinez AJ, et al: Radiotherapy of nonfunctionaladenomas of the pituitary gland, results with long-term follow up. Cancer63:2409-2414, 1989.

8. Flickinger JC, Rush SC: Linear accelerator radiotherapy of pituitaryadenomas, in Landolt AM, Vance ML, Reilly PL (eds): Pituitary Adenomas--Biology,Diagnosis and Treatment, pp 475-483. Edinburgh, Churchill Livingstone,1996.

9. Grigsby PW, Sheline G: Pituitary, in Perez CA, Brady LW (eds): Principlesand Practice of Radiation Oncology, pp 1108-1125. Philadelphia, PA, JBLippincott, 1992.

10. Flickinger JC, Deutsch M, Lunsford LD: Repeat megavoltage irradiationof pituitary and suprasellar tumors. Int J Radiat Oncol Biol Phys 17:171-175,1989.

11. Tsang RW, Brierley JD, Panzarella T, et al: Role of radiation therapyin clinical hormonally-active pituitary adenomas. Radiother Oncol 41:45-53,1996.