This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Di Sarno, A. Articles by Colao, A. Search for Related Content PubMed PubMed Citation Articles by Di Sarno, A. Articles by Colao, A.

Resistance to Cabergoline as Compared with Bromocriptine in Hyperprolactinemia: Prevalence, Clinical Definition, and Therapeutic Strategy

Department of Molecular and Clinical Endocrinology and Oncology (A.D.S., M.L.L., F.W.R., R.P., C.D.S., A.F., G.L., A.C.), Neurosurgery (P.C.), and Radiology (F.D.S.), "Federico II" University, 80131 Naples, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, via S. Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it

Abstract

To evaluate the prevalence of resistance to cabergoline treatment, we studied 120 consecutive de novo patients (56 macroadenoma, 60 microadenoma, 4 nontumoral hyperprolactinemia) treated with cabergoline (CAB) compared with 87 consecutive de novo patients (28 macroadenoma, 44 microadenoma, 15 nontumoral hyperprolactinemia) treated with bromocriptine (BRC) for 24 months. Resistance was evaluated as inability to normalize serum PRL levels (first end point) and to induce tumor shrinkage (second end point).

After 24 months, PRL normalization and tumor shrinkage after CAB and BRC treatments, respectively, were obtained in 82.1% and 46.4% of macroprolactinomas (P < 0.001) and in 90% vs. 56.8% of microprolactinomas (P < 0.001). The median doses of CAB and BRC able to fulfill the two criteria of treatment success were 1 mg/wk and 7.5 mg/d in macroprolactinomas, 1 mg/wk and 5 mg/d in microprolactinomas, and 0.5 mg/wk and 3.75 mg/d in nontumoral hyperprolactinemia. Hyperprolactinemia persisted in 17.8% of macroprolactinomas, 10% of microprolactinomas, and after CAB at doses of 5–7 mg/wk and in 53.6% of macroprolactinomas, 43.2% of microprolactinomas, and 20% of nontumoral hyperprolactinemic patients, after BRC at doses of 15–20 mg/d. In these resistant macro- and microprolactinomas, the maximal tumor diameter was reduced by 43.7 ± 3.6% and 22.1 ± 3.7% and by 59.3 ± 7.1% and 4.3 ± 2.1% after CAB and BRC, respectively (P < 0.001).

In conclusion, long-term CAB treatment induced the successful control of hyperprolactinemia associated with tumor shrinkage in a higher proportion of patients than did BRC treatment. In a small number of patients (i.e. 17.8% of macroprolactinomas and 10% of microprolactinomas), however, CAB treatment did not normalize serum PRL levels despite reducing tumor mass, even at very high doses. Therefore, an absence of tumor shrinkage cannot be considered as end point to indicate resistance to CAB, and increasing the dose of CAB higher than 3 mg/wk does not seem to be helpful in controlling PRL hypersecretion.

This article has been cited by other articles:

				E. Delgrange, T. Daems, J. Verhelst, R. Abs, and D. Maiter Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients Eur. J. Endocrinol., May 1, 2009; 160(5): 747 - 752. [Abstract] [Full Text] [PDF]

				M. E. Molitch The Cabergoline-Resistant Prolactinoma Patient: New Challenges J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4643 - 4645. [Full Text] [PDF]

				M. Ono, N. Miki, T. Kawamata, R. Makino, K. Amano, T. Seki, O. Kubo, T. Hori, and K. Takano Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4721 - 4727. [Abstract] [Full Text] [PDF]

				A. Colao, M. Galderisi, A. Di Sarno, M. Pardo, M. Gaccione, M. D'Andrea, E. Guerra, R. Pivonello, G. Lerro, and G. Lombardi Increased Prevalence of Tricuspid Regurgitation in Patients with Prolactinomas Chronically Treated with Cabergoline J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3777 - 3784. [Abstract] [Full Text] [PDF]

				C. Alvarez, I. Alonso-Muriel, G. Garcia, J. Crespo, J. Bellver, C. Simon, and A. Pellicer Implantation is apparently unaffected by the dopamine agonist Cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: a pilot study Hum. Reprod., December 1, 2007; 22(12): 3210 - 3214. [Abstract] [Full Text] [PDF]

				M. Fedele, I. De Martino, R. Pivonello, A. Ciarmiello, M. L. Del Basso De Caro, R. Visone, D. Palmieri, G. M. Pierantoni, C. Arra, H. A. Schmid, et al. SOM230, A New Somatostatin Analogue, Is Highly Effective in the Therapy of Growth Hormone/Prolactin-Secreting Pituitary Adenomas Clin. Cancer Res., May 1, 2007; 13(9): 2738 - 2744. [Abstract] [Full Text] [PDF]

				S. A. Imran, E. Ur, and D. B. Clarke Managing prolactin-secreting adenomas during pregnancy Can Fam Physician, April 1, 2007; 53(4): 653 - 658. [Abstract] [Full Text] [PDF]

				A. Gurlek, N. Karavitaki, O. Ansorge, and J. A H Wass What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics Eur. J. Endocrinol., February 1, 2007; 156(2): 143 - 153. [Abstract] [Full Text] [PDF]

				R. Gomez, M. Gonzalez-Izquierdo, R. C. Zimmermann, E. Novella-Maestre, I. Alonso-Muriel, J. Sanchez-Criado, J. Remohi, C. Simon, and A. Pellicer Low-Dose Dopamine Agonist Administration Blocks Vascular Endothelial Growth Factor (VEGF)-Mediated Vascular Hyperpermeability without Altering VEGF Receptor 2-Dependent Luteal Angiogenesis in a Rat Ovarian Hyperstimulation Model Endocrinology, November 1, 2006; 147(11): 5400 - 5411. [Abstract] [Full Text] [PDF]

				M. P. Gillam, M. E. Molitch, G. Lombardi, and A. Colao Advances in the Treatment of Prolactinomas Endocr. Rev., August 1, 2006; 27(5): 485 - 534. [Abstract] [Full Text] [PDF]

				A. Barlier and P. Jaquet Quinagolide - a valuable treatment option for hyperprolactinaemia Eur. J. Endocrinol., February 1, 2006; 154(2): 187 - 195. [Abstract] [Full Text] [PDF]

				A. Colao, G. Vitale, A. Di Sarno, S. Spiezia, E. Guerra, A. Ciccarelli, and G. Lombardi Prolactin and Prostate Hypertrophy: A Pilot Observational, Prospective, Case-Control Study in Men with Prolactinoma J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2770 - 2775. [Abstract] [Full Text] [PDF]

				A. Colao, G. Vitale, P. Cappabianca, F. Briganti, A. Ciccarelli, M. De Rosa, S. Zarrilli, and G. Lombardi Outcome of Cabergoline Treatment in Men with Prolactinoma: Effects of a 24-Month Treatment on Prolactin Levels, Tumor Mass, Recovery of Pituitary Function, and Semen Analysis J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1704 - 1711. [Abstract] [Full Text] [PDF]

				M. De Rosa, S. Zarrilli, G. Vitale, C. Di Somma, F. Orio, L. Tauchmanova', G. Lombardi, and A. Colao Six Months of Treatment with Cabergoline Restores Sexual Potency in Hyperprolactinemic Males: An Open Longitudinal Study Monitoring Nocturnal Penile Tumescence J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 621 - 625. [Abstract] [Full Text] [PDF]

				A. Colao, A. Di Sarno, P. Cappabianca, C. Di Somma, R. Pivonello, and G. Lombardi Withdrawal of Long-Term Cabergoline Therapy for Tumoral and Nontumoral Hyperprolactinemia N. Engl. J. Med., November 20, 2003; 349(21): 2023 - 2033. [Abstract] [Full Text] [PDF]

				O. Serri, C. L. Chik, E. Ur, and S. Ezzat Diagnosis and management of hyperprolactinemia Can. Med. Assoc. J., September 16, 2003; 169(6): 575 - 581. [Abstract] [Full Text]

				M. P. Gillam, S. Middler, D. J. Freed, and M. E. Molitch The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4447 - 4451. [Abstract] [Full Text] [PDF]