Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance

go back to reference Colao A, Auriemma RS, Pivonello R, Kasuki L, Gadelha MR (2016) Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary 19(3):235–247CrossRefPubMed Colao A, Auriemma RS, Pivonello R, Kasuki L, Gadelha MR (2016) Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary 19(3):235–247CrossRefPubMed

go back to reference Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, Fleseriu M, van der Lely AJ, Farrall AJ, Hermosillo Reséndiz K, Ruffin M, Chen Y, Sheppard M, Pasireotide C2305 Study Group (2014) Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 99(3):791–799CrossRefPubMedPubMedCentral Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, Fleseriu M, van der Lely AJ, Farrall AJ, Hermosillo Reséndiz K, Ruffin M, Chen Y, Sheppard M, Pasireotide C2305 Study Group (2014) Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 99(3):791–799CrossRefPubMedPubMedCentral

go back to reference Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PP, O’Carroll AM, Patel YC, Schonbrunn A, Taylor JE, Reisine T (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 16(3):86–88CrossRefPubMed Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PP, O’Carroll AM, Patel YC, Schonbrunn A, Taylor JE, Reisine T (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 16(3):86–88CrossRefPubMed

go back to reference Reisine T, Kong H, Raynor K, Yano H, Takeda J, Yasuda K, Bell GI (1993) Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase. Mol Pharmacol 44(5):1016–1020PubMed Reisine T, Kong H, Raynor K, Yano H, Takeda J, Yasuda K, Bell GI (1993) Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase. Mol Pharmacol 44(5):1016–1020PubMed

go back to reference Krantic S, Goddard I, Saveanu A, Giannetti N, Fombonne J, Cardoso A, Jaquet P, Enjalbert A (2004) Novel modalities of somatostatin actions. Eur J Endocrinol 151(6):643–655CrossRefPubMed Krantic S, Goddard I, Saveanu A, Giannetti N, Fombonne J, Cardoso A, Jaquet P, Enjalbert A (2004) Novel modalities of somatostatin actions. Eur J Endocrinol 151(6):643–655CrossRefPubMed

go back to reference Patel YC (1997) Molecular pharmacology of somatostatin receptor subtypes. J Endocrinol Invest 20(6):348–367CrossRefPubMed Patel YC (1997) Molecular pharmacology of somatostatin receptor subtypes. J Endocrinol Invest 20(6):348–367CrossRefPubMed

go back to reference Maurer R, Reubi JC (1985) Somatostatin receptors. JAMA 253(18):2741CrossRefPubMed Maurer R, Reubi JC (1985) Somatostatin receptors. JAMA 253(18):2741CrossRefPubMed

go back to reference Ben-Shlomo A, Melmed S (2010) Pituitary somatostatin receptor signaling. Trends Endocrinol Metab 21(3):123–133CrossRefPubMedPubMedCentral Ben-Shlomo A, Melmed S (2010) Pituitary somatostatin receptor signaling. Trends Endocrinol Metab 21(3):123–133CrossRefPubMedPubMedCentral

go back to reference Cordelier P, Estève JP, Bousquet C, Delesque N, O’Carroll AM, Schally AV, Vaysse N, Susini C, Buscail L (1997) Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Proc Natl Acad Sci USA 94(17):9343–9348CrossRefPubMedPubMedCentral Cordelier P, Estève JP, Bousquet C, Delesque N, O’Carroll AM, Schally AV, Vaysse N, Susini C, Buscail L (1997) Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Proc Natl Acad Sci USA 94(17):9343–9348CrossRefPubMedPubMedCentral

go back to reference Ferrante E, Pellegrini C, Bondioni S, Peverelli E, Locatelli M, Gelmini P, Luciani P, Peri A, Mantovani G, Bosari S, Beck-Peccoz P, Spada A, Lania A (2006) Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Endocr Relat Cancer 13(3):955–962CrossRefPubMed Ferrante E, Pellegrini C, Bondioni S, Peverelli E, Locatelli M, Gelmini P, Luciani P, Peri A, Mantovani G, Bosari S, Beck-Peccoz P, Spada A, Lania A (2006) Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Endocr Relat Cancer 13(3):955–962CrossRefPubMed

go back to reference Sharma K, Patel YC, Srikant CB (1996) Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 10(12):1688–1696PubMed Sharma K, Patel YC, Srikant CB (1996) Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 10(12):1688–1696PubMed

go back to reference Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146(5):707–716CrossRefPubMed Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146(5):707–716CrossRefPubMed

go back to reference Cuevas-Ramos D, Fleseriu M (2016) Pasireotide: a novel treatment for patients with acromegaly. Drug Des Dev Ther 11(10):227–239 Cuevas-Ramos D, Fleseriu M (2016) Pasireotide: a novel treatment for patients with acromegaly. Drug Des Dev Ther 11(10):227–239

go back to reference Lesche S, Lehmann D, Nagel F, Schmid HA, Schulz S (2009) Differential effects of Octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. J Clin Endocrinol Metab 94(2):654–661CrossRefPubMed Lesche S, Lehmann D, Nagel F, Schmid HA, Schulz S (2009) Differential effects of Octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. J Clin Endocrinol Metab 94(2):654–661CrossRefPubMed

go back to reference Reubi JC, Schaer JC, Waser B, Mengod G (1994) Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Res 54(13):3455–3459PubMed Reubi JC, Schaer JC, Waser B, Mengod G (1994) Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Res 54(13):3455–3459PubMed

go back to reference Murray RD, Kim K, Ren S-G, Chelly M, Umehara Y, Melmed S (2004) Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest 114(3):349–356CrossRefPubMedPubMedCentral Murray RD, Kim K, Ren S-G, Chelly M, Umehara Y, Melmed S (2004) Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest 114(3):349–356CrossRefPubMedPubMedCentral

go back to reference Fleseriu M (2011) Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary 14(2):184–193CrossRefPubMed Fleseriu M (2011) Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary 14(2):184–193CrossRefPubMed

go back to reference Roelfsema F, Biermasz NR, Pereira AM, Romijn JA (2008) Therapeutic options in the management of acromegaly: focus on Lanreotide Autogel. Biologics 2(3):463–479PubMedPubMedCentral Roelfsema F, Biermasz NR, Pereira AM, Romijn JA (2008) Therapeutic options in the management of acromegaly: focus on Lanreotide Autogel. Biologics 2(3):463–479PubMedPubMedCentral

go back to reference Mazziotti G, Giustina A (2010) Effects of Lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13(1):60–67CrossRefPubMed Mazziotti G, Giustina A (2010) Effects of Lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13(1):60–67CrossRefPubMed

go back to reference Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S (2012) Meta-analysis on the effects of Octreotide on tumor mass in acromegaly. PLoS ONE 7(5):e36411CrossRefPubMedPubMedCentral Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S (2012) Meta-analysis on the effects of Octreotide on tumor mass in acromegaly. PLoS ONE 7(5):e36411CrossRefPubMedPubMedCentral

go back to reference Cuevas-Ramos D, Fleseriu M (2014) Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. J Mol Endocrinol 52(3):R223–R240CrossRefPubMed Cuevas-Ramos D, Fleseriu M (2014) Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. J Mol Endocrinol 52(3):R223–R240CrossRefPubMed

go back to reference Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA, Endocrine Society (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951CrossRefPubMed Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA, Endocrine Society (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951CrossRefPubMed

go back to reference Arafat AM, Mohlig M, Weickert MO, Perschel FH, Purschwitz J, Spranger J, Strasburger CJ, Schöfl C, Pfeiffer AF (2008) Growth hormone response during OGTT: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls and the role of gender, age and BMI. J Clin Endocrinol Metab 93(4):1254–1262CrossRefPubMed Arafat AM, Mohlig M, Weickert MO, Perschel FH, Purschwitz J, Spranger J, Strasburger CJ, Schöfl C, Pfeiffer AF (2008) Growth hormone response during OGTT: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls and the role of gender, age and BMI. J Clin Endocrinol Metab 93(4):1254–1262CrossRefPubMed

go back to reference Clemmons DR (2007) IGF-I assays: current assay methodologies and their limitations. Pituitary 10(2):121–128CrossRefPubMed Clemmons DR (2007) IGF-I assays: current assay methodologies and their limitations. Pituitary 10(2):121–128CrossRefPubMed

go back to reference Colao A, Auriemma RS, Lombardi G, Pivonello R (2011) Resistance to somatostatin analogs in acromegaly. Endocr Rev 32(2):247–271CrossRefPubMed Colao A, Auriemma RS, Lombardi G, Pivonello R (2011) Resistance to somatostatin analogs in acromegaly. Endocr Rev 32(2):247–271CrossRefPubMed

go back to reference Besser GM, Burman P, Daly AF (2005) Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol 153(2):187–193CrossRefPubMed Besser GM, Burman P, Daly AF (2005) Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol 153(2):187–193CrossRefPubMed

go back to reference Casarini AP, Pinto EM, Jallad RS, Giorgi RR, Giannella Neto D, Bronstein MD (2006) Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest 29(9):826–830CrossRefPubMed Casarini AP, Pinto EM, Jallad RS, Giorgi RR, Giannella Neto D, Bronstein MD (2006) Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest 29(9):826–830CrossRefPubMed

go back to reference Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, Caranci F, Cirillo S, Lombardi G (2006) Predictors of tumor shrinkage after primary therapy with somatostatin analogues in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 91(6):2112–2118CrossRefPubMed Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, Caranci F, Cirillo S, Lombardi G (2006) Predictors of tumor shrinkage after primary therapy with somatostatin analogues in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 91(6):2112–2118CrossRefPubMed

go back to reference Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Grasso LF, Lombardi G (2008) Growth hormone-secreting tumor shrinkage after 3 months of Octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab 93(9):3436–3442CrossRefPubMed Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Grasso LF, Lombardi G (2008) Growth hormone-secreting tumor shrinkage after 3 months of Octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab 93(9):3436–3442CrossRefPubMed

go back to reference Melmed S (2006) Medical progress: acromegaly. N Engl J Med 355(24):2558–2573CrossRefPubMed Melmed S (2006) Medical progress: acromegaly. N Engl J Med 355(24):2558–2573CrossRefPubMed

go back to reference Sherlock M, Fernandez-Rodriguez E, Alonso AA, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM (2009) Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab 94(4):1255–1263CrossRefPubMed Sherlock M, Fernandez-Rodriguez E, Alonso AA, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM (2009) Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab 94(4):1255–1263CrossRefPubMed

go back to reference Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M (2013) Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary 16(4):490–498CrossRefPubMed Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M (2013) Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary 16(4):490–498CrossRefPubMed

go back to reference Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, Bollerslev J (2012) Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin Endocrinol (Oxf) 77(1):72–78CrossRef Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, Bollerslev J (2012) Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin Endocrinol (Oxf) 77(1):72–78CrossRef

go back to reference Plöckinger U, Bäder M, Hopfenmüller W, Saeger W, Quabbe HJ (1997) Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to octreotide therapy and do not correlate with tumor histology. Eur J Endocrinol 136(4):369–376CrossRefPubMed Plöckinger U, Bäder M, Hopfenmüller W, Saeger W, Quabbe HJ (1997) Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to octreotide therapy and do not correlate with tumor histology. Eur J Endocrinol 136(4):369–376CrossRefPubMed

go back to reference Reubi JC, Landolt AM (1989) The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status. J Clin Endocrinol Metab 68(4):844–850CrossRefPubMed Reubi JC, Landolt AM (1989) The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status. J Clin Endocrinol Metab 68(4):844–850CrossRefPubMed

go back to reference Plöckinger U, Albrecht S, Mawrin C, Saeger W, Buchfelder M, Petersenn S, Schulz S (2008) Selective loss of somatostatin receptor 2 in octreotide-resistant growth hormone-secreting adenomas. J Clin Endocrinol Metab 93(4):1203–1210CrossRefPubMed Plöckinger U, Albrecht S, Mawrin C, Saeger W, Buchfelder M, Petersenn S, Schulz S (2008) Selective loss of somatostatin receptor 2 in octreotide-resistant growth hormone-secreting adenomas. J Clin Endocrinol Metab 93(4):1203–1210CrossRefPubMed

go back to reference Bertherat J, Chanson P, Dewailly D, Dupuy M, Jaquet P, Peillon F, Epelbaum J (1993) Somatostatin receptors, adenylate cyclase activity, and growth hormone (GH) response to octreotide in GH-secreting adenomas. J Clin Endocrinol Metab 77(6):1577–1583PubMed Bertherat J, Chanson P, Dewailly D, Dupuy M, Jaquet P, Peillon F, Epelbaum J (1993) Somatostatin receptors, adenylate cyclase activity, and growth hormone (GH) response to octreotide in GH-secreting adenomas. J Clin Endocrinol Metab 77(6):1577–1583PubMed

go back to reference Gatto F, Biermasz NR, Feelders RA, Kros JM, Dogan F, van der Lely AJ, Neggers SJ, Lamberts SW, Pereira AM, Ferone D, Hofland LJ (2016) Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. Eur J Endocrinol 174(5):651–662CrossRefPubMed Gatto F, Biermasz NR, Feelders RA, Kros JM, Dogan F, van der Lely AJ, Neggers SJ, Lamberts SW, Pereira AM, Ferone D, Hofland LJ (2016) Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. Eur J Endocrinol 174(5):651–662CrossRefPubMed

go back to reference Peverelli E, Treppiedi D, Giardino E, Vitali E, Lania AG, Mantovani G (2015) Dopamine and somatostatin analogues resistance of pituitary tumors: focus on cytoskeleton involvement. Front Endocrinol (Lausanne) 6:187 Peverelli E, Treppiedi D, Giardino E, Vitali E, Lania AG, Mantovani G (2015) Dopamine and somatostatin analogues resistance of pituitary tumors: focus on cytoskeleton involvement. Front Endocrinol (Lausanne) 6:187

go back to reference Rocheville M, Lange DC, Kumar U, Sasi R, Patel RC, Patel YC (2000) Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem 275(11):7862–7869CrossRefPubMed Rocheville M, Lange DC, Kumar U, Sasi R, Patel RC, Patel YC (2000) Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem 275(11):7862–7869CrossRefPubMed

go back to reference Taboada GF, Luque RM, Neto LV, Machado Ede O, Sbaffi BC, Domingues RC, Marcondes JB, Chimelli LM, Fontes R, Niemeyer P, de Carvalho DP, Kineman RD, Gadelha MR (2008) Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol 158(3):295–303CrossRefPubMed Taboada GF, Luque RM, Neto LV, Machado Ede O, Sbaffi BC, Domingues RC, Marcondes JB, Chimelli LM, Fontes R, Niemeyer P, de Carvalho DP, Kineman RD, Gadelha MR (2008) Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol 158(3):295–303CrossRefPubMed

go back to reference Jaquet P, Gunz G, Saveanu A, Dufour H, Taylor J, Dong J, Kim S, Moreau JP, Enjalbert A, Culler MD (2005) Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy. Eur J Endocrinol 153(1):135–141CrossRefPubMed Jaquet P, Gunz G, Saveanu A, Dufour H, Taylor J, Dong J, Kim S, Moreau JP, Enjalbert A, Culler MD (2005) Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy. Eur J Endocrinol 153(1):135–141CrossRefPubMed

go back to reference Zatelli MC, Piccin D, Tagliati F, Ambrosio MR, Margutti A, Padovani R, Scanarini M, Culler MD, degli Uberti EC (2003) Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH, and PRL secretion. J Clin Endocrinol Metab 88(6):2797–2802CrossRefPubMed Zatelli MC, Piccin D, Tagliati F, Ambrosio MR, Margutti A, Padovani R, Scanarini M, Culler MD, degli Uberti EC (2003) Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH, and PRL secretion. J Clin Endocrinol Metab 88(6):2797–2802CrossRefPubMed

go back to reference Ballarè E, Persani L, Lania AG, Filopanti M, Giammona E, Corbetta S, Mantovani S, Arosio M, Beck-Peccoz P, Faglia G, Spada A (2001) Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. J Clin Endocrinol Metab 86(8):3809–3814CrossRefPubMed Ballarè E, Persani L, Lania AG, Filopanti M, Giammona E, Corbetta S, Mantovani S, Arosio M, Beck-Peccoz P, Faglia G, Spada A (2001) Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. J Clin Endocrinol Metab 86(8):3809–3814CrossRefPubMed

go back to reference Ciganoka D, Balcere I, Kapa I, Peculis R, Valtere A, Nikitina-Zake L, Lase I, Schiöth HB, Pirags V, Klovins J (2011) Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly. Eur J Endocrinol 165(4):517–525CrossRefPubMedPubMedCentral Ciganoka D, Balcere I, Kapa I, Peculis R, Valtere A, Nikitina-Zake L, Lase I, Schiöth HB, Pirags V, Klovins J (2011) Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly. Eur J Endocrinol 165(4):517–525CrossRefPubMedPubMedCentral

go back to reference Filopanti M, Ballarè E, Lania AG, Bondioni S, Verga U, Locatelli M, Zavanone LM, Losa M, Gelmini S, Peri A, Orlando C, Beck-Peccoz P (2004) Spada A (2004) Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary tumors. J Endocrinol Invest 27(10):937–942CrossRefPubMed Filopanti M, Ballarè E, Lania AG, Bondioni S, Verga U, Locatelli M, Zavanone LM, Losa M, Gelmini S, Peri A, Orlando C, Beck-Peccoz P (2004) Spada A (2004) Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary tumors. J Endocrinol Invest 27(10):937–942CrossRefPubMed

go back to reference Marina D, Burman P, Klose M, Casar-Borota O, Luque RM, Castaño JP, Feldt-Rasmussen U (2015) Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues—observations in two patients with acromegaly and severe headache. Growth Horm IGF Res 25(5):262–267CrossRefPubMed Marina D, Burman P, Klose M, Casar-Borota O, Luque RM, Castaño JP, Feldt-Rasmussen U (2015) Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues—observations in two patients with acromegaly and severe headache. Growth Horm IGF Res 25(5):262–267CrossRefPubMed

go back to reference Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M (1990) Faglia G (1990) Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71(6):1421–1426CrossRefPubMed Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M (1990) Faglia G (1990) Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71(6):1421–1426CrossRefPubMed

go back to reference Larkin S, Reddy R, Karavitaki N, Cudlip S, Wass J, Ansorge O (2013) Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur J Endocrinol 168(4):491–499CrossRefPubMed Larkin S, Reddy R, Karavitaki N, Cudlip S, Wass J, Ansorge O (2013) Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur J Endocrinol 168(4):491–499CrossRefPubMed

go back to reference Ballarè E, Mantovani S, Bassetti M, Lania AG, Spada A (1997) Immunodetection of G proteins in human pituitary adenomas: evidence for a low expression of proteins of the Gi subfamily. Eur J Endocrinol 137(5):482–489CrossRefPubMed Ballarè E, Mantovani S, Bassetti M, Lania AG, Spada A (1997) Immunodetection of G proteins in human pituitary adenomas: evidence for a low expression of proteins of the Gi subfamily. Eur J Endocrinol 137(5):482–489CrossRefPubMed

go back to reference Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML, Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, Cazabat L, De Menis E, Montañana CF, Raverot G, Weil RJ, Sane T, Maiter D, Neggers S, Yaneva M, Tabarin A, Verrua E, Eloranta E, Murat A, Vierimaa O, Salmela PI, Emy P, Toledo RA, Sabaté MI, Villa C, Popelier M, Salvatori R, Jennings J, Longás AF, Labarta Aizpún JI, Georgitsi M, Paschke R, Ronchi C, Valimaki M, Saloranta C, De Herder W, Cozzi R, Guitelman M, Magri F, Lagonigro MS, Halaby G, Corman V, Hagelstein MT, Vanbellinghen JF, Barra GB, Gimenez-Roqueplo AP, Cameron FJ, Borson-Chazot F, Holdaway I, Toledo SP, Stalla GK, Spada A, Zacharieva S, Bertherat J, Brue T, Bours V, Chanson P, Aaltonen LA, Beckers A (2010) Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab 95(11):E373–E383CrossRefPubMed Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML, Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, Cazabat L, De Menis E, Montañana CF, Raverot G, Weil RJ, Sane T, Maiter D, Neggers S, Yaneva M, Tabarin A, Verrua E, Eloranta E, Murat A, Vierimaa O, Salmela PI, Emy P, Toledo RA, Sabaté MI, Villa C, Popelier M, Salvatori R, Jennings J, Longás AF, Labarta Aizpún JI, Georgitsi M, Paschke R, Ronchi C, Valimaki M, Saloranta C, De Herder W, Cozzi R, Guitelman M, Magri F, Lagonigro MS, Halaby G, Corman V, Hagelstein MT, Vanbellinghen JF, Barra GB, Gimenez-Roqueplo AP, Cameron FJ, Borson-Chazot F, Holdaway I, Toledo SP, Stalla GK, Spada A, Zacharieva S, Bertherat J, Brue T, Bours V, Chanson P, Aaltonen LA, Beckers A (2010) Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab 95(11):E373–E383CrossRefPubMed

go back to reference Dénes J, Kasuki L, Trivellin G, Colli LM, Takiya CM, Stiles CE, Barry S, de Castro M, Gadelha MR, Korbonits M (2015) Regulation of aryl hydrocarbon receptor interacting protein (AIP) protein expression by MiR-34a in sporadic somatotropinomas. PLoS ONE 10(2):e0117107CrossRefPubMedPubMedCentral Dénes J, Kasuki L, Trivellin G, Colli LM, Takiya CM, Stiles CE, Barry S, de Castro M, Gadelha MR, Korbonits M (2015) Regulation of aryl hydrocarbon receptor interacting protein (AIP) protein expression by MiR-34a in sporadic somatotropinomas. PLoS ONE 10(2):e0117107CrossRefPubMedPubMedCentral

go back to reference Gadelha MR, Kasuki L, Korbonits M (2013) Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol Metab 24(5):238–246CrossRefPubMed Gadelha MR, Kasuki L, Korbonits M (2013) Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol Metab 24(5):238–246CrossRefPubMed

go back to reference Tuominen I, Heliövaara E, Raitila A, Rautiainen MR, Mehine M, Katainen R, Donner I, Aittomäki V, Lehtonen HJ, Ahlsten M, Kivipelto L, Schalin-Jäntti C, Arola J, Hautaniemi S, Karhu A (2014) AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling. Oncogene 34(9):1174–1184CrossRefPubMed Tuominen I, Heliövaara E, Raitila A, Rautiainen MR, Mehine M, Katainen R, Donner I, Aittomäki V, Lehtonen HJ, Ahlsten M, Kivipelto L, Schalin-Jäntti C, Arola J, Hautaniemi S, Karhu A (2014) AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling. Oncogene 34(9):1174–1184CrossRefPubMed

go back to reference Iacovazzo D, Carlsen E, Lugli F, Chiloiro S, Piacentini S, Bianchi A, Giampietro A, Mormando M, Clear AJ, Doglietto F, Anile C, Maira G, Lauriola L, Rindi G, Roncaroli F, Pontecorvi A, Korbonits M, De Marinis L (2016) Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol 174(2):241–250CrossRefPubMed Iacovazzo D, Carlsen E, Lugli F, Chiloiro S, Piacentini S, Bianchi A, Giampietro A, Mormando M, Clear AJ, Doglietto F, Anile C, Maira G, Lauriola L, Rindi G, Roncaroli F, Pontecorvi A, Korbonits M, De Marinis L (2016) Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol 174(2):241–250CrossRefPubMed

go back to reference Theodoropoulou M, Stalla GK, Spengler D (2010) ZAC1 target genes and pituitary tumorigenesis. Mol Cell Endocrinol 326(1–2):60–65CrossRefPubMed Theodoropoulou M, Stalla GK, Spengler D (2010) ZAC1 target genes and pituitary tumorigenesis. Mol Cell Endocrinol 326(1–2):60–65CrossRefPubMed

go back to reference Fougner SL, Lekva T, Borota OC, Hald JK, Bollerslev J, Berg JP (2010) The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. J Clin Endocrinol Metab 95(5):2334–2342CrossRefPubMed Fougner SL, Lekva T, Borota OC, Hald JK, Bollerslev J, Berg JP (2010) The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. J Clin Endocrinol Metab 95(5):2334–2342CrossRefPubMed

go back to reference Fougner SL, Bollerslev J, Latif F, Hald JK, Lund T, Ramm-Pettersen J, Berg JP (2008) Low levels of raf kinase inhibitory protein in growth hormone-secreting pituitary adenomas correlate with poor response to octreotide treatment. J Clin Endocrinol Metab 93(4):1211–1216CrossRefPubMed Fougner SL, Bollerslev J, Latif F, Hald JK, Lund T, Ramm-Pettersen J, Berg JP (2008) Low levels of raf kinase inhibitory protein in growth hormone-secreting pituitary adenomas correlate with poor response to octreotide treatment. J Clin Endocrinol Metab 93(4):1211–1216CrossRefPubMed