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Published in: Pituitary 4/2011

01-12-2011 | Case Report

Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma

Authors: Alessandra Fusco, Francesca Lugli, Eugenia Sacco, Laura Tilaro, Antonio Bianchi, Flavia Angelini, Anna Tofani, Angela Barini, Libero Lauriola, Giulio Maira, Alfredo Pontecorvi, Laura de Marinis

Published in: Pituitary | Issue 4/2011

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Abstract

Prolactinomas in males can be voluminous macroadenomas invading the surrounding structures. Medical therapy with dopamine agonists (the treatment of choice for these tumours) may be ineffective in the case of pharmacological resistance. In such cases, even surgical and/or radiation therapy cannot be curative due to the invasive potential of the adenoma. Hence, the appropriate therapeutic approach for these tumours is still a relevant clinical problem for endocrinologists. We report the history of an adolescent male who was diagnosed with a large invasive macroprolactinoma in 2002. He had severe bitemporal hemianopsia and hypopituitarism; prolactin levels at diagnosis were higher than 8,000 ng/ml. Medical therapy with cabergoline was initiated and resulted in decreased prolactin levels but not complete normalisation (maximal tolerated dose 3 mg/day). However, due to the worsening of the visual defect, the patient was operated in July 2004 through the trans-nasal approach and 2 years later through both the transcranial and the transphenoidal approaches. After the second surgery, a significant reduction of tumour mass was obtained. Immunohistochemistry for somatostatin receptors (sstr) subtypes showed a positive staining with the anti-sstr5 antibody. A scintigraphy with 111In-pentetreotide (Octreoscan) revealed a very intense tracer uptake in the sellar region. The administration of long-acting octreotide was initiated. After 12 months of therapy, prolactin levels normalised for the first time. Pituitary MRI did not reveal any tumor progression during a 2-year follow-up. This is a case of an invasive dopamine-resistant macroprolactinoma that was successfully controlled by extensive surgery and combined treatment with cabergoline and octreotide. The expression and functionality of sstr should be investigated in these tumours since a combined therapy with cabergoline and octreotide may be a good therapeutic course of action for select cases.
Literature
1.
go back to reference Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao AM, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 65:265–273. doi:10.1111/j.1365-2265.2006.02562.x CrossRef Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao AM, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 65:265–273. doi:10.​1111/​j.​1365-2265.​2006.​02562.​x CrossRef
2.
go back to reference Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225PubMed Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225PubMed
3.
go back to reference Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, Di Somma C, Faggiano AG, Lombardi G, Colao AM (2001) Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition and therapeutic strategy. J Clin Endocrinol Metab 86:5256–5261. doi:10.1210/jc.86.11.5256 PubMedCrossRef Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, Di Somma C, Faggiano AG, Lombardi G, Colao AM (2001) Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition and therapeutic strategy. J Clin Endocrinol Metab 86:5256–5261. doi:10.​1210/​jc.​86.​11.​5256 PubMedCrossRef
6.
go back to reference Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP, Kordon C, Peillon F, Jaquet P, Enjalbert A (1989) Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab 69:500–509PubMedCrossRef Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP, Kordon C, Peillon F, Jaquet P, Enjalbert A (1989) Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab 69:500–509PubMedCrossRef
8.
go back to reference Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horwath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–106. doi:10.1097/00006123-199601000-00024 PubMedCrossRef Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horwath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–106. doi:10.​1097/​00006123-199601000-00024 PubMedCrossRef
9.
go back to reference Delgrange E, Sassolas G, Perrin G, Jan M, Trouillas J (2005) Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance. Acta Neurochir (Wien) 147:751–758. doi:10.1007/s00701-005-0498-2 CrossRef Delgrange E, Sassolas G, Perrin G, Jan M, Trouillas J (2005) Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance. Acta Neurochir (Wien) 147:751–758. doi:10.​1007/​s00701-005-0498-2 CrossRef
11.
go back to reference Greenman Y, Melmed S (1994) Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. J Clin Endocrinol Metab 79:724–729. doi:10.1210/jc.79.3.724 PubMedCrossRef Greenman Y, Melmed S (1994) Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. J Clin Endocrinol Metab 79:724–729. doi:10.​1210/​jc.​79.​3.​724 PubMedCrossRef
12.
go back to reference Murabe H, Shimatsu A, Ihara C, Mizuta H, Nakamura Y, Nagata I, Kikuchi H, Nakao K (1996) Expression of somatostatin receptor (SSTR) subtypes in pituitary adenomas: quantitative analysis of SSTR2 mRNA by reverse transcription-polymerase chain reaction. J Neuroendocrinol 8:605–610. doi:10.1111/j.1365-2826.1996.tb00695.x PubMedCrossRef Murabe H, Shimatsu A, Ihara C, Mizuta H, Nakamura Y, Nagata I, Kikuchi H, Nakao K (1996) Expression of somatostatin receptor (SSTR) subtypes in pituitary adenomas: quantitative analysis of SSTR2 mRNA by reverse transcription-polymerase chain reaction. J Neuroendocrinol 8:605–610. doi:10.​1111/​j.​1365-2826.​1996.​tb00695.​x PubMedCrossRef
13.
go back to reference Jaquet P, Quafik L, Saveanu A, Gunz G, Fina F, Dufour H, Culler MD, Moreau JP, Enjalbert A (1999) Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 84:3268–3276. doi:10.1210/jc.84.9.3268 PubMedCrossRef Jaquet P, Quafik L, Saveanu A, Gunz G, Fina F, Dufour H, Culler MD, Moreau JP, Enjalbert A (1999) Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 84:3268–3276. doi:10.​1210/​jc.​84.​9.​3268 PubMedCrossRef
15.
go back to reference Lamberts SWJ, Krenning EP, Reubi JC (1991) The role of somatostatin and its analogues in the diagnosis and treatment of tumours. Endocr Rev 12:450–482PubMedCrossRef Lamberts SWJ, Krenning EP, Reubi JC (1991) The role of somatostatin and its analogues in the diagnosis and treatment of tumours. Endocr Rev 12:450–482PubMedCrossRef
17.
go back to reference Colao A, Lastoria S, Ferone D, Varrella P, Marzullo P, Pivonello R, Cerbone G, Acampa W, Salvatore M, Lombardi G (1999) The pituitary uptake of 111In-DPTA-DPhe1-octreotide in the normal pituitary and in pituitary adenomas. J Endocrinol Invest 22:176–183PubMed Colao A, Lastoria S, Ferone D, Varrella P, Marzullo P, Pivonello R, Cerbone G, Acampa W, Salvatore M, Lombardi G (1999) The pituitary uptake of 111In-DPTA-DPhe1-octreotide in the normal pituitary and in pituitary adenomas. J Endocrinol Invest 22:176–183PubMed
18.
go back to reference Acosta-Gomez MJ, Muros MA, Llamas-elvira JM, Ramirez A, Ortega S, Sabatel G, Ramos C, a Aguilar A (2005) The role of somatostatin receptor scintigraphy in patients with pituitari adenoma or post-surgical recurrent tumours. Br J Radiol 78:110–115. doi:10.1259/bjr/51245688 PubMedCrossRef Acosta-Gomez MJ, Muros MA, Llamas-elvira JM, Ramirez A, Ortega S, Sabatel G, Ramos C, a Aguilar A (2005) The role of somatostatin receptor scintigraphy in patients with pituitari adenoma or post-surgical recurrent tumours. Br J Radiol 78:110–115. doi:10.​1259/​bjr/​51245688 PubMedCrossRef
19.
go back to reference Shimon I, Yan X, Taylor JE, Weiss MH, Culler MD, Melmed S (1997) Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. J Clin Invest 100:2386–2392. doi:10.1172/JCI119779 PubMedCrossRef Shimon I, Yan X, Taylor JE, Weiss MH, Culler MD, Melmed S (1997) Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. J Clin Invest 100:2386–2392. doi:10.​1172/​JCI119779 PubMedCrossRef
20.
go back to reference Hofland LJ, de Herder WW, Visser-Visselaar HA, van Uffelen C, Waaijers M, Zuyderwijk J, Uitterlinden P, Kros MJM, van Koetsveld PM, Lamberts WJ (1997) Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release on a small subgroup of pituitary- and islet cell tumours. J Clin Endocrinol Metab 82:3011–3018. doi:10.1210/jc.82.9.3011 PubMedCrossRef Hofland LJ, de Herder WW, Visser-Visselaar HA, van Uffelen C, Waaijers M, Zuyderwijk J, Uitterlinden P, Kros MJM, van Koetsveld PM, Lamberts WJ (1997) Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release on a small subgroup of pituitary- and islet cell tumours. J Clin Endocrinol Metab 82:3011–3018. doi:10.​1210/​jc.​82.​9.​3011 PubMedCrossRef
21.
go back to reference Ishibashi M, Yamaji T (1985) Mechanism of the inhibitory action of dopamine and somatostatin on prolactin secretion from human lactotrophs in culture. J Clin Endocrinol Metab 60:599–606PubMedCrossRef Ishibashi M, Yamaji T (1985) Mechanism of the inhibitory action of dopamine and somatostatin on prolactin secretion from human lactotrophs in culture. J Clin Endocrinol Metab 60:599–606PubMedCrossRef
22.
go back to reference Hofland LJ, van der Hoek J, van Koetsveld PM, de Herder WW, Waaijers M, Sprij-Mooji D, Bruns C, Weckbecker G, Feelders R, van der Lely AJ, Beckers A, Lamberts WJ (2004) The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro. J Clin Endocrinol Metab 89:1577–1585. doi:10.1210/jc.2003-031344 PubMedCrossRef Hofland LJ, van der Hoek J, van Koetsveld PM, de Herder WW, Waaijers M, Sprij-Mooji D, Bruns C, Weckbecker G, Feelders R, van der Lely AJ, Beckers A, Lamberts WJ (2004) The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro. J Clin Endocrinol Metab 89:1577–1585. doi:10.​1210/​jc.​2003-031344 PubMedCrossRef
23.
go back to reference Murray RD, Kim K, Ren SG, Lewis I, Weckbecker G, Brun C, Melmed S (2004) The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion. J Clin Endocrinol Metab 89:3027–3032. doi:10.1210/jc.2003-031319 PubMedCrossRef Murray RD, Kim K, Ren SG, Lewis I, Weckbecker G, Brun C, Melmed S (2004) The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion. J Clin Endocrinol Metab 89:3027–3032. doi:10.​1210/​jc.​2003-031319 PubMedCrossRef
24.
go back to reference Lamberts SW, Zweens M, Klijn JG, van Vroonhoven CC, Stefanko SZ, Del Pozo E (1986) The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201–995 in patients with prolactinomas and acromegaly. Clin Endocrinol (Oxf) 25:201–212. doi:10.1111/j.1365-2265.1986.tb01683.x CrossRef Lamberts SW, Zweens M, Klijn JG, van Vroonhoven CC, Stefanko SZ, Del Pozo E (1986) The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201–995 in patients with prolactinomas and acromegaly. Clin Endocrinol (Oxf) 25:201–212. doi:10.​1111/​j.​1365-2265.​1986.​tb01683.​x CrossRef
25.
go back to reference Bronstein MD, Knoepfelmacher M, Liberman B, Marino R Jr, Germek OA, Shally AV (1987) Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia. Horm Metab Res 19:271–274. doi:10.1055/s-2007-1011796 PubMedCrossRef Bronstein MD, Knoepfelmacher M, Liberman B, Marino R Jr, Germek OA, Shally AV (1987) Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia. Horm Metab Res 19:271–274. doi:10.​1055/​s-2007-1011796 PubMedCrossRef
26.
go back to reference Grottoli S, Gasco V, Broglio F, Baldelli R, Ragazzoni F, Gallenca F, Mainolfi A, Prodam F, Muccioli G, Ghigo E (2006) Cortistatin-17 and Somatostatin-14 display the same effects on growth hormone, prolactin and insulin secretion in patients with acromegaly or prolactinoma. J Clin Endocrinol Metab 91:1595–1599. doi:10.1210/jc.2005-1837 PubMedCrossRef Grottoli S, Gasco V, Broglio F, Baldelli R, Ragazzoni F, Gallenca F, Mainolfi A, Prodam F, Muccioli G, Ghigo E (2006) Cortistatin-17 and Somatostatin-14 display the same effects on growth hormone, prolactin and insulin secretion in patients with acromegaly or prolactinoma. J Clin Endocrinol Metab 91:1595–1599. doi:10.​1210/​jc.​2005-1837 PubMedCrossRef
28.
go back to reference Gruszka A, Ren SG, Dong J, Culler MD, Melmed S (2007) Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules. Endocrinology 148:6107–6114. doi:10.1210/en.2007-0378 PubMedCrossRef Gruszka A, Ren SG, Dong J, Culler MD, Melmed S (2007) Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules. Endocrinology 148:6107–6114. doi:10.​1210/​en.​2007-0378 PubMedCrossRef
29.
go back to reference Fusco A, Gunz G, Jaquet P, Dufour H, Germanetti AL, Culler MD, Barlier A, Saveanu A (2008) Somatostatinergic ligands in dopamine-sensitive and resistant prolactinomas. Eur J Endocrinol 158:595–603. doi:10.1530/EJE-07-0806 PubMedCrossRef Fusco A, Gunz G, Jaquet P, Dufour H, Germanetti AL, Culler MD, Barlier A, Saveanu A (2008) Somatostatinergic ligands in dopamine-sensitive and resistant prolactinomas. Eur J Endocrinol 158:595–603. doi:10.​1530/​EJE-07-0806 PubMedCrossRef
30.
32.
go back to reference Kars M, Delgado V, Holman ER, Feelders RA, Smit JW, Romijn JA, Bax JJ, Pereira AM (2008) Aortic valve calcification and mild tricuspid regurgitation, but no clinical heart disease after 8 years of dopamine agonist therapy for prolactinoma. J Clin Endocrinol Metab 93(9):3348–3356. doi:10.1210/jc.2007-2658 PubMedCrossRef Kars M, Delgado V, Holman ER, Feelders RA, Smit JW, Romijn JA, Bax JJ, Pereira AM (2008) Aortic valve calcification and mild tricuspid regurgitation, but no clinical heart disease after 8 years of dopamine agonist therapy for prolactinoma. J Clin Endocrinol Metab 93(9):3348–3356. doi:10.​1210/​jc.​2007-2658 PubMedCrossRef
33.
go back to reference Wakil A, Rigby A, Clark A, Atkin S (2008) Low dose cabergoline for hyperprolactinemia is not associated with clinically significant valvular heart disease. Eur J Endocrinol 159(4):R11–R14 Epub 2008 Jul 14PubMedCrossRef Wakil A, Rigby A, Clark A, Atkin S (2008) Low dose cabergoline for hyperprolactinemia is not associated with clinically significant valvular heart disease. Eur J Endocrinol 159(4):R11–R14 Epub 2008 Jul 14PubMedCrossRef
34.
go back to reference Colao A, Galderisi M, Di Sarno A, Pardo M, Gaccione M, D’Andrea M, Guerra E, Pivonello R, Lerro G, Lombardi G (2008) Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline. J Clin Endocrinol Metab 93(10):3777–3784. doi:10.1210/jc.2007-1403 PubMedCrossRef Colao A, Galderisi M, Di Sarno A, Pardo M, Gaccione M, D’Andrea M, Guerra E, Pivonello R, Lerro G, Lombardi G (2008) Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline. J Clin Endocrinol Metab 93(10):3777–3784. doi:10.​1210/​jc.​2007-1403 PubMedCrossRef
Metadata
Title
Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma
Authors
Alessandra Fusco
Francesca Lugli
Eugenia Sacco
Laura Tilaro
Antonio Bianchi
Flavia Angelini
Anna Tofani
Angela Barini
Libero Lauriola
Giulio Maira
Alfredo Pontecorvi
Laura de Marinis
Publication date
01-12-2011
Publisher
Springer US
Published in
Pituitary / Issue 4/2011
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-008-0162-y

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