In Vitro Head-to-Head Comparison Between Octreotide and Pasireotide in GH-Secreting Pituitary Adenomas

被引:57
作者
Gatto, Federico [1 ]
Feelders, Richard A. [1 ,2 ]
Franck, Sanne E. [1 ]
van Koetsveld, Peter M. [1 ]
Dogan, Fadime [1 ]
Kros, Johan M. [2 ,3 ]
Neggers, Sebastian J. C. M. M. [1 ,2 ]
van der Lely, Aart-Jan [1 ,2 ]
Lamberts, Steven W. J. [1 ]
Ferone, Diego [4 ]
Hofland, Leo J. [1 ,2 ]
机构
[1] Erasmus Univ, Div Endocrinol, Dept Internal Med, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[2] Erasmus Univ, Pituitary Ctr Rotterdam, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[3] Erasmus Univ, Dept Pathol, Med Ctr, NL-3000 CA Rotterdam, Netherlands
[4] Univ Genoa, Endocrinol Sect, Dept Internal Med & Med Specialties, Ctr Excellence Biomed Res, I-16126 Genoa, Italy
关键词
SOMATOSTATIN RECEPTOR SUBTYPES; GENE-EXPRESSION LEVELS; CORTICOTROPH ADENOMAS; MONOCLONAL-ANTIBODIES; QUANTITATIVE-ANALYSIS; HORMONE-SECRETION; POTENT INHIBITOR; ANALOG SOM230; EFFICACY; THERAPY;
D O I
10.1210/jc.2017-00135
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly. Objective: To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile. Design: The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples. Setting and Patients: Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands). Interventions: OCT and PAS treatment for 72 hours (10 nM). Main Outcome Measures: GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples. Results: The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)(2) messenger RNA (mRNA) and sst(2)/sst(5) mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01). Conclusions: Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst(2) mRNA expression and lower sst(2)/sst(5) mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly.
引用
收藏
页码:2009 / 2018
页数:10
相关论文
共 34 条
[1]   The 2004 World Health Organization classification of pituitary tumors: What is new? [J].
Al-Shraim, M ;
Asa, SL .
ACTA NEUROPATHOLOGICA, 2006, 111 (01) :1-7
[2]   SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile [J].
Bruns, C ;
Lewis, I ;
Briner, U ;
Meno-Tetang, G ;
Weckbecker, G .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2002, 146 (05) :707-716
[3]   Acromegaly Clinical Trial Methodology Impact on Reported Biochemical Efficacy Rates of Somatostatin Receptor Ligand Treatments: A Meta-Analysis [J].
Carmichael, John D. ;
Bonert, Vivien S. ;
Nuno, Miriam ;
Ly, Diana ;
Melmed, Shlomo .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (05) :1825-1833
[4]   Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in Somatotroph Adenomas Assessed by Monoclonal Antibodies Was Reduced by Octreotide and Correlated With the Acute and Long-Term Effects of Octreotide [J].
Casar-Borota, Olivera ;
Heck, Ansgar ;
Schulz, Stefan ;
Nesland, Jahn Marthin ;
Ramm-Pettersen, Jon ;
Lekva, Tove ;
Alafuzoff, Irina ;
Bollerslev, Jens .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (11) :E1730-E1739
[5]   Agonist-Biased Signaling at the sst2A Receptor: The Multi-Somatostatin Analogs KE108 and SOM230 Activate and Antagonize Distinct Signaling Pathways [J].
Cescato, Renzo ;
Loesch, Kimberly A. ;
Waser, Beatrice ;
Maecke, Helmut R. ;
Rivier, Jean E. ;
Reubi, Jean Claude ;
Schonbrunn, Agnes .
MOLECULAR ENDOCRINOLOGY, 2010, 24 (01) :240-249
[6]   Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies [J].
Chinezu, Laura ;
Vasiljevic, Alexandre ;
Jouanneau, Emmanuel ;
Francois, Patrick ;
Borda, Angela ;
Trouillas, Jacqueline ;
Raverot, Gerald .
HUMAN PATHOLOGY, 2014, 45 (01) :71-77
[7]   Pasireotide Versus Octreotide in Acromegaly: A Head-to-Head Superiority Study [J].
Colao, A. ;
Bronstein, M. D. ;
Freda, P. ;
Gu, F. ;
Shen, C. -C. ;
Gadelha, M. ;
Fleseriu, M. ;
van der Lely, A. J. ;
Farrall, A. J. ;
Resendiz, K. Hermosillo ;
Ruffin, M. ;
Chen, Y. ;
Sheppard, M. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (03) :791-799
[8]   Resistance to Somatostatin Analogs in Acromegaly [J].
Colao, Annamaria ;
Auriemma, Renata S. ;
Lombardi, Gaetano ;
Pivonello, Rosario .
ENDOCRINE REVIEWS, 2011, 32 (02) :247-271
[9]   Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas [J].
de Bruin, Christiaan ;
Pereira, Alberto M. ;
Feelders, Richard A. ;
Romijn, Johannes A. ;
Roelfsema, Ferdinand ;
Sprij-Mooij, Diane M. ;
van Aken, Maarten O. ;
van der Lelij, Aart-Jan ;
de Herder, Wouter W. ;
Lamberts, Steven W. J. ;
Hofland, Leo J. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (04) :1118-1124
[10]   Medical Therapy of Acromegaly Efficacy and Safety of Somatostatin Analogues [J].
Feelders, Richard A. ;
Hofland, Leo J. ;
van Aken, Maarten O. ;
Neggers, Sebastian J. ;
Lamberts, Steven W. J. ;
de Herder, Wouter W. ;
van der Lely, Aart-Jan .
DRUGS, 2009, 69 (16) :2207-2226