{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T18:08:52Z","timestamp":1783361332435,"version":"3.54.6"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Hamburg-Eppendorf (UKE)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hormones"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To analyze the expression of somatostatin receptor (SSTR)2a and 5 by immunohistochemistry (IHC) in surgically resected somatotrophic pituitary adenomas and to associate expression rates with tumor size and clinical, biochemical, and histological parameters and response to somatostatin analog (SA) therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Forty-three microsurgically treated patients with histopathologically proven growth hormone (GH)\u2013producing pituitary adenoma were included (WHO 2017). SSTR subtype expression was analyzed in adenoma tissues using monoclonal antibodies (Abcam, SSTR2a-UMB1, SSTR5-UMB4). Expression rates were classified as low (\u2264\u200920% staining positivity), moderate (21\u201350%), and high (&gt;\u200950%). Furthermore, biochemical parameters such as human growth hormone (hGH) and insulin-like growth factor-1 (IGF-1) levels were measured and clinical, biochemical, radiological, and histological data were evaluated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the 43 patients included in this study, 28 were female and 15 were male. The median age was 52\u00a0years (range 17\u201372\u00a0years). The median tumor size was 1.2\u00a0cm (range: 0.13\u20133.93\u00a0cm). All resected tumors showed positivity for somatotrophic hormone (STH). In all tissue samples, SSTR2a signal expression was detectable in immunohistochemistry, while only 39 samples were positive for SSTR5. Thirty-six samples had a high expression of SSTR2a, while three had a moderate and four a low SSTR2a signal. In comparison, SSTR5 signal was high in 26 out of 43 samples, while seven adenomas showed a moderate and six cases a low expression rate of SSTR5. The median IGF-1 was 714.2\u00a0\u00b5g\/l and the median GH 19.6\u00a0mU\/l (=\u20096.53\u00a0\u00b5g\/l). The present study indicates that there is no significant relationship between the expression rates of receptor subtypes and the parameters we analyzed. However, our study revealed that smaller adenomas have a lower baseline GH level (<jats:italic>p<\/jats:italic>\u2009=\u20090.015),<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>IHC with monoclonal antibodies appears to be a suitable method to determine the expression rates of SSTR2a and 5 at protein levels, as it is not possible to draw conclusions regarding receptor subtypes solely on the basis of the parameters analyzed.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s42000-021-00327-w","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T12:02:36Z","timestamp":1634817756000},"page":"79-89","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted therapy?"],"prefix":"10.1007","volume":"21","author":[{"given":"Lena","family":"Rass","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir-Hossein","family":"Rahvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Matschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Saeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Renn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Aberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Flitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-5317","authenticated-orcid":false,"given":"Roman","family":"Rotermund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"issue":"2","key":"327_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.17925\/EE.2018.14.2.57","volume":"14","author":"R Zahr","year":"2018","unstructured":"Zahr R, Fleseriu M (2018) \u2018Updates in diagnosis and treatment of acromegaly.\u2019 Eur. Endocrinol 14(2):57. https:\/\/doi.org\/10.17925\/EE.2018.14.2.57","journal-title":"Eur Endocrinol"},{"issue":"5","key":"327_CR2","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.beem.2009.05.010","volume":"23","author":"P Chanson","year":"2009","unstructured":"Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J (2009) Acromegaly. Best Pract Res Clin Endocrinol Metab 23(5):555\u2013574. https:\/\/doi.org\/10.1016\/j.beem.2009.05.010","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"1","key":"327_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1023\/A:1009965803750","volume":"2","author":"IM Holdaway","year":"1999","unstructured":"Holdaway IM, Rajasoorya C (1999) Epidemiology of acromegaly. Pituitary 2(1):29\u201341. https:\/\/doi.org\/10.1023\/A:1009965803750","journal-title":"Pituitary"},{"issue":"1","key":"327_CR4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40360-017-0124-y","volume":"18","author":"MH Gurel","year":"2017","unstructured":"Gurel MH, Han Y, Stevens AL, Furtado A, Cox D (2017) Treatment adherence and persistence with long-acting somatostatin analog therapy for the treatment of acromegaly: a retrospective analysis. BMC Pharmacol Toxicol 18(1):22. https:\/\/doi.org\/10.1186\/s40360-017-0124-y","journal-title":"BMC Pharmacol Toxicol"},{"issue":"11","key":"327_CR5","doi-asserted-by":"publisher","first-page":"3933","DOI":"10.1210\/jc.2014-2700","volume":"99","author":"L Katznelson","year":"2014","unstructured":"Katznelson L et al (2014) Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933\u20133951. https:\/\/doi.org\/10.1210\/jc.2014-2700","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"327_CR6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1080\/01616412.2017.1296653","volume":"39","author":"V Briceno","year":"2017","unstructured":"Briceno V et al (2017) Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis. Neurol Res 39(5):387\u2013398. https:\/\/doi.org\/10.1080\/01616412.2017.1296653","journal-title":"Neurol Res"},{"issue":"1","key":"327_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1055\/s-0033-1354578","volume":"75","author":"H Sun","year":"2014","unstructured":"Sun H, Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M (2014) Factors associated with biochemical remission after microscopic transsphenoidal surgery for acromegaly. J Neurol Surg Part B Skull Base 75(1):47\u201352. https:\/\/doi.org\/10.1055\/s-0033-1354578","journal-title":"J Neurol Surg Part B Skull Base"},{"issue":"11","key":"327_CR8","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S2213-8587(14)70169-X","volume":"2","author":"MR Gadelha","year":"2014","unstructured":"Gadelha MR et al (2014) Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol 2(11):875\u2013884. https:\/\/doi.org\/10.1016\/S2213-8587(14)70169-X","journal-title":"Lancet Diabetes Endocrinol"},{"key":"327_CR9","doi-asserted-by":"publisher","unstructured":"Shimon et al (2017) Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control\u2019. HORMONES 16(1). https:\/\/doi.org\/10.14310\/horm.2002.1722","DOI":"10.14310\/horm.2002.1722"},{"issue":"1","key":"327_CR10","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000448429","volume":"105","author":"SE Franck","year":"2017","unstructured":"Franck SE et al (2017) Somatostatin receptor expression in GH-secreting pituitary adenomas treated with long-acting somatostatin analogues in combination with Pegvisomant. Neuroendocrinol 105(1):44\u201353. https:\/\/doi.org\/10.1159\/000448429","journal-title":"Neuroendocrinol"},{"issue":"7","key":"327_CR11","doi-asserted-by":"publisher","first-page":"3013","DOI":"10.1210\/jcem.87.7.8665","volume":"87","author":"PU Freda","year":"2002","unstructured":"Freda PU (2002) Somatostatin analogs in acromegaly. J Clin Endocrinol Metab 87(7):3013\u20133018. https:\/\/doi.org\/10.1210\/jcem.87.7.8665","journal-title":"J Clin Endocrinol Metab"},{"key":"327_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/9606985","volume":"2017","author":"W Liu","year":"2017","unstructured":"Liu W et al (2017) Expression of somatostatin receptor 2 in somatotropinoma correlated with the short-term efficacy of somatostatin analogues. Int J Endocrinol 2017:1\u20137. https:\/\/doi.org\/10.1155\/2017\/9606985","journal-title":"Int J Endocrinol"},{"issue":"11","key":"327_CR13","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1172\/JCI39375","volume":"119","author":"S Melmed","year":"2009","unstructured":"Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Invest 119(11):3189\u20133202. https:\/\/doi.org\/10.1172\/JCI39375","journal-title":"J Clin Invest"},{"issue":"3","key":"327_CR14","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1210\/jc.2013-2480","volume":"99","author":"A Colao","year":"2014","unstructured":"Colao A et al (2014) Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 99(3):791\u2013799. https:\/\/doi.org\/10.1210\/jc.2013-2480","journal-title":"J Clin Endocrinol Metab"},{"issue":"1\u20132","key":"327_CR15","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1159\/000381460","volume":"102","author":"SL Samson","year":"2015","unstructured":"Samson SL (2015) Pasireotide in acromegaly: an overview of current mechanistic and clinical data. Neuroendocrinol 102(1\u20132):8\u201317. https:\/\/doi.org\/10.1159\/000381460","journal-title":"Neuroendocrinol"},{"issue":"5","key":"327_CR16","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1530\/eje.0.1460707","volume":"146","author":"C Bruns","year":"2002","unstructured":"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\u2013716. https:\/\/doi.org\/10.1530\/eje.0.1460707","journal-title":"Eur J Endocrinol"},{"key":"327_CR17","doi-asserted-by":"publisher","unstructured":"Fleseriu M, Cuevas-Ramos D (2016) Pasireotide: a novel treatment for patients with acromegaly. Drug Des Devel Ther. 227. https:\/\/doi.org\/10.2147\/DDDT.S77999.","DOI":"10.2147\/DDDT.S77999"},{"issue":"3","key":"327_CR18","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1136\/jcp.2005.026914","volume":"59","author":"E Thodou","year":"2006","unstructured":"Thodou E (2006) Mapping of somatostatin receptor types in GH or\/and PRL producing pituitary adenomas. J Clin Pathol 59(3):274\u2013279. https:\/\/doi.org\/10.1136\/jcp.2005.026914","journal-title":"J Clin Pathol"},{"issue":"4","key":"327_CR19","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s11102-009-0175-1","volume":"12","author":"APM Casarini","year":"2009","unstructured":"Casarini APM et al (2009) Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. Pituitary 12(4):297\u2013303. https:\/\/doi.org\/10.1007\/s11102-009-0175-1","journal-title":"Pituitary"},{"issue":"13","key":"327_CR20","first-page":"3455","volume":"54","author":"JC Reubi","year":"1994","unstructured":"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\u20133459","journal-title":"Cancer Res"},{"issue":"11","key":"327_CR21","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1038\/modpathol.3800954","volume":"20","author":"M Volante","year":"2007","unstructured":"Volante M et al (2007) Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 20(11):1172\u20131182. https:\/\/doi.org\/10.1038\/modpathol.3800954","journal-title":"Mod Pathol"},{"issue":"2","key":"327_CR22","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/PAS.0b013e31823d07f3","volume":"36","author":"M K\u00f6rner","year":"2012","unstructured":"K\u00f6rner M, Waser B, Schonbrunn A, Perren A, Reubi JC (2012) \u2018Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting\u2019: Am. J Surg Pathol 36(2):242\u2013252. https:\/\/doi.org\/10.1097\/PAS.0b013e31823d07f3","journal-title":"J Surg Pathol"},{"issue":"3","key":"327_CR23","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1159\/000329876","volume":"94","author":"A Lupp","year":"2011","unstructured":"Lupp A, Hunder A, Petrich A, Nagel F, Doll C, Schulz S (2011) Reassessment of sst5 somatostatin receptor expression in normal and neoplastic human tissues using the novel rabbit monoclonal antibody UMB-4. Neuroendocrinology 94(3):255\u2013264. https:\/\/doi.org\/10.1159\/000329876","journal-title":"Neuroendocrinology"},{"issue":"11","key":"327_CR24","doi-asserted-by":"publisher","first-page":"4519","DOI":"10.1210\/jc.2008-1063","volume":"93","author":"T Fischer","year":"2008","unstructured":"Fischer T, Doll C, Jacobs S, Kolodziej A, Stumm R, Schulz S (2008) Reassessment of sst 2 somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-1. J Clin Endocrinol Metab 93(11):4519\u20134524. https:\/\/doi.org\/10.1210\/jc.2008-1063","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"327_CR25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.humpath.2013.08.007","volume":"45","author":"L Chinezu","year":"2014","unstructured":"Chinezu L et al (2014) Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies. Hum Pathol 45(1):71\u201377. https:\/\/doi.org\/10.1016\/j.humpath.2013.08.007","journal-title":"Hum Pathol"},{"issue":"3","key":"327_CR26","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1046\/j.1365-2362.2001.00786.x","volume":"31","author":"S Corbetta","year":"2001","unstructured":"Corbetta S et al (2001) Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression. Eur J Clin Invest 31(3):208\u2013214. https:\/\/doi.org\/10.1046\/j.1365-2362.2001.00786.x","journal-title":"Eur J Clin Invest"},{"issue":"2","key":"327_CR27","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1210\/jcem.85.2.6338","volume":"85","author":"P Jaquet","year":"2000","unstructured":"Jaquet P et al (2000) Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes 1. J Clin Endocrinol Metab 85(2):781\u2013792. https:\/\/doi.org\/10.1210\/jcem.85.2.6338","journal-title":"J Clin Endocrinol Metab"},{"key":"327_CR28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.mce.2015.09.016","volume":"417","author":"K Kiseljak-Vassiliades","year":"2015","unstructured":"Kiseljak-Vassiliades K et al (2015) Differential somatostatin receptor (SSTR) 1\u20135 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors. Mol Cell Endocrinol 417:73\u201383. https:\/\/doi.org\/10.1016\/j.mce.2015.09.016","journal-title":"Mol Cell Endocrinol"},{"issue":"3","key":"327_CR29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1507\/endocrj.ej11-0177","volume":"59","author":"M Kato","year":"2012","unstructured":"Kato M et al (2012) Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. Endocr J 59(3):221\u2013228. https:\/\/doi.org\/10.1507\/endocrj.ej11-0177","journal-title":"Endocr J"},{"issue":"2","key":"327_CR30","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1677\/jme.1.01876","volume":"35","author":"MC Zatelli","year":"2005","unstructured":"Zatelli MC et al (2005) Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro. J Mol Endocrinol 35(2):333\u2013341. https:\/\/doi.org\/10.1677\/jme.1.01876","journal-title":"J Mol Endocrinol"},{"issue":"2","key":"327_CR31","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s10549-005-2414-0","volume":"92","author":"U Kumar","year":"2005","unstructured":"Kumar U et al (2005) Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1\u20135 and correlation with receptor protein expression and tumor pathology. Breast Cancer Res Treat 92(2):175\u2013186. https:\/\/doi.org\/10.1007\/s10549-005-2414-0","journal-title":"Breast Cancer Res Treat"},{"issue":"5","key":"327_CR32","doi-asserted-by":"publisher","first-page":"963","DOI":"10.3892\/mmr.2011.519","volume":"4","author":"H Pisarek","year":"2011","unstructured":"Pisarek H, Krupi\u0144ski R, Kubiak R, Borkowska E, Pawlikowski M, Winczyk K (2011) Differential expression of somatostatin receptor subtype-related genes and proteins in non-functioning and functioning adrenal cortex adenomas. Mol Med Rep 4(5):963\u2013969. https:\/\/doi.org\/10.3892\/mmr.2011.519","journal-title":"Mol Med Rep"},{"issue":"4","key":"327_CR33","first-page":"240","volume":"60","author":"H Pisarek","year":"2009","unstructured":"Pisarek H, Pawlikowski M, Kunert-Radek J, Radek M (2009) Expression of somatostatin receptor subtypes in human pituitary adenomas \u2013 immunohistochemical studies. Endokrynol Pol 60(4):240\u2013251","journal-title":"Endokrynol Pol"},{"key":"327_CR34","doi-asserted-by":"publisher","unstructured":"de Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C, (2009) Global signatures of protein and mRNA expression levels. Mol Biosyst 10.1039.b908315d. https:\/\/doi.org\/10.1039\/b908315d.","DOI":"10.1039\/b908315d"},{"issue":"11","key":"327_CR35","doi-asserted-by":"publisher","first-page":"E1730","DOI":"10.1210\/jc.2013-2145","volume":"98","author":"O Casar-Borota","year":"2013","unstructured":"Casar-Borota O et al (2013) 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 Clin Endocrinol Metab 98(11):E1730\u2013E1739. https:\/\/doi.org\/10.1210\/jc.2013-2145","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"327_CR36","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1159\/000330616","volume":"95","author":"HA Schmid","year":"2012","unstructured":"Schmid HA et al (2012) Monoclonal antibodies against the human somatostatin receptor subtypes 1\u20135: development and immunohistochemical application in neuroendocrine tumors. Neuroendocrinology 95(3):232\u2013247. https:\/\/doi.org\/10.1159\/000330616","journal-title":"Neuroendocrinology"},{"issue":"2","key":"327_CR37","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1210\/jcem.84.2.5497","volume":"84","author":"LJ Hofland","year":"1999","unstructured":"Hofland LJ et al (1999) Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors. J Clin Endocrinol Metab 84(2):775\u2013780. https:\/\/doi.org\/10.1210\/jcem.84.2.5497","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"327_CR38","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/j.1365-2265.2007.03065.x","volume":"68","author":"SL Fougner","year":"2008","unstructured":"Fougner SL, Borota OC, Berg JP, Hald JK, Ramm-Pettersen J, Bollerslev J (2008) The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma. Clin Endocrinol (Oxf) 68(3):458\u2013465. https:\/\/doi.org\/10.1111\/j.1365-2265.2007.03065.x","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"327_CR39","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1530\/EJE-13-0134","volume":"169","author":"B Mayr","year":"2013","unstructured":"Mayr B, Buslei R, Theodoropoulou M, Stalla GK, Buchfelder M, Sch\u00f6fl C (2013) Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas. Eur J Endocrinol 169(4):391\u2013400. https:\/\/doi.org\/10.1530\/EJE-13-0134","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"327_CR40","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1210\/jc.2007-1986","volume":"93","author":"U Pl\u00f6ckinger","year":"2008","unstructured":"Pl\u00f6ckinger U et al (2008) Selective loss of somatostatin receptor 2 in octreotide-resistant growth hormone-secreting adenomas. J Clin Endocrinol Metab 93(4):1203\u20131210. https:\/\/doi.org\/10.1210\/jc.2007-1986","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"327_CR41","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/s11102-012-0445-1","volume":"16","author":"J Brzana","year":"2013","unstructured":"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\u2013498. https:\/\/doi.org\/10.1007\/s11102-012-0445-1","journal-title":"Pituitary"},{"issue":"4","key":"327_CR42","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1210\/jcem.86.4.7398","volume":"86","author":"GA Kaltsas","year":"2001","unstructured":"Kaltsas GA et al (2001) Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity. J Clin Endocrinol Metab 86(4):1645\u20131652. https:\/\/doi.org\/10.1210\/jcem.86.4.7398","journal-title":"J Clin Endocrinol Metab"},{"key":"327_CR43","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ghir.2018.03.002","volume":"41","author":"R Rotermund","year":"2018","unstructured":"Rotermund R, Burkhardt T, Rohani Z, Jung R, Aberle J, Flitsch J (2018) Value of early postoperative random growth hormone levels and nadir growth hormone levels after oral glucose tolerance testing in acromegaly. Growth Horm IGF Res 41:64\u201370. https:\/\/doi.org\/10.1016\/j.ghir.2018.03.002","journal-title":"Growth Horm IGF Res"},{"key":"327_CR44","doi-asserted-by":"publisher","unstructured":"Kim EH, Oh MC, Lee EJ, Kim SH (2012)Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly. Neurosurgery 70(5):1106\u20131113. https:\/\/doi.org\/10.1227\/NEU.0b013e31823f5c16.","DOI":"10.1227\/NEU.0b013e31823f5c16"},{"issue":"3","key":"327_CR45","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1046\/j.1365-2265.2003.01900.x","volume":"60","author":"JA Takahashi","year":"2004","unstructured":"Takahashi JA, Shimatsu A, Nakao K, Hashimoto N (2004) Early postoperative indicators of late outcome in acromegalic patients. Clin Endocrinol (Oxf) 60(3):366\u2013374. https:\/\/doi.org\/10.1046\/j.1365-2265.2003.01900.x","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"1","key":"327_CR46","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s12020-014-0383-y","volume":"49","author":"K Kiseljak-Vassiliades","year":"2015","unstructured":"Kiseljak-Vassiliades K et al (2015) Growth hormone tumor histological subtypes predict response to surgical and medical therapy. Endocrine 49(1):231\u2013241. https:\/\/doi.org\/10.1007\/s12020-014-0383-y","journal-title":"Endocrine"},{"issue":"2","key":"327_CR47","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1007\/s12022-008-9029-z","volume":"19","author":"A Obari","year":"2008","unstructured":"Obari A et al (2008) Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol 19(2):82\u201391. https:\/\/doi.org\/10.1007\/s12022-008-9029-z","journal-title":"Endocr Pathol"},{"issue":"4","key":"327_CR48","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1530\/EJE-10-0586","volume":"163","author":"Y Bakhtiar","year":"2010","unstructured":"Bakhtiar Y et al (2010) Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae. Eur J Endocrinol 163(4):531\u2013539. https:\/\/doi.org\/10.1530\/EJE-10-0586","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"327_CR49","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/j.1365-2265.2011.04163.x","volume":"76","author":"SL Fougner","year":"2012","unstructured":"Fougner SL, Casar-Borota O, Heck A, Berg JP, Bollerslev J (2012) Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol (Oxf) 76(1):96\u2013102. https:\/\/doi.org\/10.1111\/j.1365-2265.2011.04163.x","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"6","key":"327_CR50","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1530\/eje.0.1330686","volume":"133","author":"S Ezzat","year":"1995","unstructured":"Ezzat S, Kontogeorgos G, Redelmeier DA, Horvath E, Harris AG, Kovacs K (1995) In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. Eur J Endocrinol 133(6):686\u2013690. https:\/\/doi.org\/10.1530\/eje.0.1330686","journal-title":"Eur J Endocrinol"},{"key":"327_CR51","unstructured":"Mazal et al Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients - PubMed. https:\/\/pubmed.ncbi.nlm.nih.gov\/11495005\/ (Accessed 16 Sep 2020)."},{"key":"327_CR52","doi-asserted-by":"publisher","unstructured":"Bando H, et al (1992) Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma. Endocrinol Jpn 39(4):355\u2013363. https:\/\/doi.org\/10.1507\/endocrj1954.39.355","DOI":"10.1507\/endocrj1954.39.355"}],"container-title":["Hormones"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42000-021-00327-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s42000-021-00327-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42000-021-00327-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:34:40Z","timestamp":1645785280000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s42000-021-00327-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,21]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["327"],"URL":"https:\/\/doi.org\/10.1007\/s42000-021-00327-w","relation":{},"ISSN":["1109-3099","2520-8721"],"issn-type":[{"value":"1109-3099","type":"print"},{"value":"2520-8721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,21]]},"assertion":[{"value":"21 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics committee of the medical board Hamburg and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}