Abstract
The medical treatment of pituitary adenomas has changed significantly over the past decade. Pharmacologic therapy for prolactinomas in the form of dopamine agonists has been available since the 1970s, and somatostatin analogues for treatment of growth hormone (GH)-secreting adenomas were introduced in the 1980s. However, the recent introduction of long-acting forms of these agents has markedly improved efficacy. Furthermore, long-acting somatostatin analogues also have utility in treating thyrotropin adenomas and a subset of adrenocorticotroph tumors. Limited clinical studies with long-acting dopamine agonists suggest that a subset of patients with GH, adrenocorticotroph, and gonadotropin/ nonsecreting adenomas may also benefit from therapy with these agents. The introduction of a GH receptor antagonist in the 1990s has added to the pharmacologic armamentarium for treatment of acromegaly. In parallel with improved medical therapy, hormonal assays for assessing tumor activity have improved in sensitivity, necessitating new standards for treatment optimization. This article highlights some of these evolving new ideas and approaches to the pharmacologic management of pituitary adenomas.
Similar content being viewed by others
References and Recommended Reading
Barker FG, Klibanski A, Swearingen B: Transphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 2003, 88:4709–4719.
Vance ML: Medical therapy of functional pituitary tumors. In Neurosurgery Clinics of North America, vol. 14. Edited by Cauldwell WT, Weiss M. Philadelphia: WB Saunders; 2003:81–87.
Molitch ME: Medical treatment of prolactinomas. In Endocrinology and Metabolism Clinics of North America. Advances in Pituitary Tumor Therapy, vol. 28. Edited by Molitch ME. Philadelphia: WB Saunders; 1999:143–169.
Pickett CA: Diagnosis and management of pituitary tumors: recent advances. In Primary Care: Clinics in Office Practice. Endocrinology Part II: General Endocrinology, vol. 30. Edited by DeWitt DE. Philadelphia: WB Saunders; 2003:765–789.
Petrovich Z, Jozsef G, Yu C, Appuzzo ML: Radiotherapy and stereotactic radiosurgery for pituitary tumors. Neurosurg Clin North Am 2003, 14:147–166.
Brabant G, von zur Muhlen R, Wuster C, et al.: Serum insulinlike growth factor-I reference values for an automated chemiluminsecence immunoassay system: results from multicenter study. Hormone Res 2003, 60(Suppl 2):53–60.
Giustina A, Barkan A, Casanueva F, et al.: Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 2000, 85:526–529. This is the consensus statement from an international conference of pituitary experts regarding guidelines for establishing cure in acromegaly.
Holdaway IM: Treatment of acromegaly. Hormone Res 2004, 62:79–92.
Pokrajac-Simeunovic A, Trainer PJ: Pitfalls in the diagnosis of acromegaly. Hormone Res 2004, 62:74–78. This article summarizes recent studies utilizing new GH assays in the diagnosis and management of acromegaly and suggests a stricter criteria for excess GH secretion.
Freda PU, Nuruzzaman AT, Reyes CM, et al.: Significance of ‘abnormal’ nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 2004, 89:495–500.
Costa AC, Rossi A, Martinelli CE Jr, et al.: Assessment of disease activity in treated acromegalic patients using a sensitive GH assay: should we achieve strict normal GH levels for a biochemical cure? J Clin Endocrinol Metab 2002, 87:3142–3147.
Serri O, Beauregard C, Hardy J: Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly. J Clin Endocrinol Metab 2004, 89:658–661.
Dimaraki EV, Jaffe CA, DeMott-Friberg R, et al.: Acromegaly with apparently normal GH secretion: implication for diagnosis and follow-up. J Clin Endocrinol Metab 2002, 87:3537–3542.
Growth Hormone Research Society; Pituitary Society: Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and the Pituitary Society. J Clin Endocrinol Metab 2004, 89:3099–3102. This is a report from a second consensus conference on criteria for establishing remission in GH-secreting adenomas, recognizing new advances in assay methodologies, and standards for IGF and GH.
Yap LB, Turner HE, Adams CB, et al.: Undetectable postoperative cortisol does not always predict long-term remission in Cushing’s disease: a single center audit. Clin Endocrinol 2002, 56:25–31. This study highlights the false-negative rate of the undetectable postoperative serum cortisol levels in long-term follow-up of patients with Cushing’s disease and the need for vigilance in monitoring for recurrence.
Rollin GA, Ferreira NP, Junges M, et al.: Dynamics of serum cortisol levels after transphenoidal surgery in a cohort of patients with Cushing’s disease. J Clin Endocrinol Metab 2004, 89:1131–1139.
Chee GH, Mathias D, James RA, et al.: Transsphenoidal pituitary surgery in Cushing’s disease: Can we predict outcome? Clin Endocrinol 2001, 54:617–626.
Findling JW, Raff H, Aron DC: The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome. J Clin Endocrinol Metab 2004, 89:1222–1226.
Newell-Price J: Transsphenoidal surgery for Cushing’s disease: defining cure and following outcome. Clin Endocrinol 2002, 56:19–21.
Nieman LK: Medical therapy of Cushing’s disease. Pituitary 2002, 5:77–82. This is an indispensable review of current drug therapy for ACTHsecreting adenomas, particularly focusing on adrenal steroidogenesis inhibitors, covering both the mechanism of action and practical recommendations for clinical use.
Muller AF, Van Der Lely AJ: Pharmacological therapy for acromegaly: a critical review. Drugs 2004, 64:1817–1838. This is an excellent in-depth review of current pharmacologic therapy for GH-secreting adenomas, including current somatostatin analogues and the GH-receptor antagonist pegvisomant.
Amato G, Mazziotti G, Rotondi M, et al.: Long-term effects of lanreotide SR and octreotide LAR on tumor shrinkage and GH hypersecretion in patients with previously untreated acromegaly. Clin Endocrinol 2002, 56:65–71.
Heijckmann CA, Menheere PP, Sels JP, et al.: Clinical experience with Sandostatin LAR in patients with acromegaly. Neth J Med 2001, 59:286–291.
Caron P: Somatuline Autogel, a new formulation of lanreotide for the treatment of acromegalic patients. Ann Endocrinol 2002, 63:2S19–2S24.
Oberg K: Future aspects of somatostatin-receptor-mediated therapy. Neuroendocrinology 2004, 80:57–61.
Arafah BM, Nasrallah MP: Pituitary tumors: pathophysiology, clinical manifestations and management. Endocrinol Relat Cancer 2001, 8:287–305.
Cozzi R, Attanasio R, Lodrini S, Lasio G: Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status. Clin Endocrinol 2004, 61:209–215. This is a recent study of the efficacy of the long-acting dopamine antagonist in treating resistant acromegalic patients. It also reviews the literature on dopamine receptor status in GH-secreting tumors.
Marzullo P, Ferone D, Di Somma C, et al.: Efficacy of combined treatment with lanreotide and cabergoline in selected therapyresistant acromegalic patients. Pituitary 1999, 1:115–120.
Kopchick JJ, Parkinson C, Stevens EC, et al.: Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocrinol Rev 2002, 23:623–646. This is an excellent review of the development of the novel GH-receptor antagonist pegvisomant and its pharmacologic properties.
Muller AF, van der Lely AJ: Insights from growth hormone receptor blockade. Curr Opin Investig Drugs 2004, 5:1082–1079.
Trainer PJ, Drake WM, Katznelson L, et al.: Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000, 342:1171–1177.
van der Lely AJ, Hutson RK, Trainer PJ, et al.: Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001, 38:1754–1759.
Drake WM, Parkinson C, Besser GM, et al.: Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly. Trends Endocrinol Metab 2001, 12:408–413.
Herman-Bonert VS, Zib K, Scarlett JA, et al.: Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J Clin Endocrinol Metab 2000, 85:2958–2961.
Parkinson C, Trainer PJ: The place of pegvisomant in the management of acromegaly. Exp Opin Investig Drugs 2001, 10:1725–1735. This article discusses the clinical use of pegvisomant in conjunction with other current therapies for GH-secreting adenomas.
Clemmons DR, Chihara K, Freda PU, et al.: Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm. J Clin Endocrinol Metab 2003, 88:4759–4767. This article summarizes the consensus of a group of internationally recognized GH experts regarding the use of pegvisomant in current therapy of GH-secreting adenomas.
Paez-Pereda M, Artz E, Stalla GK: Cushing’s syndrome: drug targets and therapeutic options. Exp Opin Ther Patients 2002, 12:1537–1546. This is an excellent in-depth review of current pharmacologic options for treatment of Cushing’s syndrome, including discussion of potential targets for development of new therapies.
Pivonello R, Perone D, de Herder WW, et al.: Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab 2004, 89:2452–2462. This is a recent study of the efficacy of cabergoline in treating ACTHsecreting adenomas, including analysis of D2 receptor expression in predicting response.
Heaney AP, Fernando M, Melmed S: PPAR-g receptor ligands: novel therapy for pituitary adenomas. J Clin Invest 2003, 111:1381–1388.
Cannavo S, Ambrosi B, Chiodini I, et al.: Baseline and CRHstimulated ACTH and cortisol levels after administration of the peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone, in Cushing’s disease. J Endocrinol Invest 2004, 27:RC8-RC11.
Ambrosi B, Dall’Asta C, Cannavo S, et al.: Effects of chronic administration of PPAR-gamma ligand rosiglitazone in Cushing’s disease. Eur J Endcorinol 2004, 151:173–178.
Turner HE, Stratton IM, Byrne J, et al.: Audit of selected patients with nonfunctioning pituitary adenomas without irradiation—a follow-up study. Clin Endocrinol 1999, 51:281–284.
Shomali ME, Katznelson L: Medical therapy for gonadotroph and thyrotroph tumors. In Endocrinology and Metabolism Clinics of North America. Advances in Pituitary Tumor Therapy, vol. 28. Edited by Molitch ME. Philadelphia: WB Saunders; 1999:223–240.
Pivonello R, Matrone C, Filipella M, et al.: Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. J Clin Endocrinol Metab 2004, 89:1674–1683. This is a recent study of the efficacy of cabergoline in treating gonadotropin/ nonfunctioning pituitary adenomas, including analysis of D2 receptor expression in predicting response.
de Herder WW, Reifs AR, de Swart JK, et al.: Comparison of iodine-123 epdepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas. Eur J Nucl Med 1999, 26:46–50.
Colao A, Di Sarno A, Marzullo P, et al.: New medical approaches in pituitary adenomas. Horm Res 2000, 53:76–87.
Lohmann T, Trantakis C, Biesold M, et al.: Minor tumor shrinkage in non-functioning pituitary adenomas by long-term treatment with the dopamine agonist cabergoline. Pituitary 2001, 4:173–178.
Colao A, Fernone D, Lastoria S, et al.: Hormone levels and tumor size response to quinagolide and cabergoline in patients with prolactin-secreting and clinically non-functioning pituitary adenomas: predictive value of pituitary scintigraphy with 123Imetoxybenzamide. Clin Endocrinol 2000, 52:437–452.
Beck-Peccoz P, Brucker-Davis F, Persani R, et al.: Thyrotropinsecreting pituitary adenomas. Endocrinol Rev 1996, 17:610–638.
Caron P, Arlot S, Bauter C, et al.: Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 2001, 86:2849–2853.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pickett, C.A. Update on the medical management of pituitary adenomas. Curr Neurol Neurosci Rep 5, 178–185 (2005). https://doi.org/10.1007/s11910-005-0045-9
Issue Date:
DOI: https://doi.org/10.1007/s11910-005-0045-9