Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 ( = 0.024, r = 0.49) and E-Cadherin ( = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 ( = 0.107, r = -0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.
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http://dx.doi.org/10.3390/ijms25168663 | DOI Listing |
Pituitary
December 2024
Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Purpose: Acromegaly patients occasionally achieve either of the remission criterion of IGF-1 or GH level postoperatively; however, treatment for patients with discordant IGF-1 and GH levels remains unclear. This study aimed to clarify the clinical courses and features of postoperative patients with normal IGF-1 and high GH levels and support their management.
Methods: Overall, 110 acromegaly patients underwent initial surgery and a 75-g oral glucose tolerance test (OGTT) 3 months postoperatively.
Pituitary
December 2024
Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Milan, Italy.
Introduction: First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of acromegaly treatment. Additional benefits were shown using high dose (HD) or high frequency (HF), relatively short-term regimens. Although several predictors of response to standard dose (SD)-fg-SRLs were reported, outcome biomarkers for HF administration are not yet available.
View Article and Find Full Text PDFPituitary
December 2024
Computational Neuroscience Outcomes Center, Harvard Medical School, Boston, Massachusetts, USA.
Purpose: The objective of this study was to characterize the clinical characteristics and factors predictive of biochemical remission in patients with symptomatic acromegaly undergoing transsphenoidal surgery (TSS) at an academic tertiary care center, as defined by the 2022 Acromegaly Consensus Conference guidelines.
Methods: In this single institution, longitudinal, retrospective study, a large cohort of 158 patients with a preoperative diagnosis of acromegaly undergoing surgery at a large, academic, tertiary care center were examined. We excluded 38 patients as IGF-1 testing was performed less than 12 weeks postoperatively.
Eur J Endocrinol
December 2024
Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, Genova, Italy.
Immunohistochemistry of somatostatin receptor subtype 2 (SSTR2) can predict response to first-generation somatostatin receptor ligands (fg-SRLs) in acromegaly. Recently, we validated an open-source digital image analysis (DIA) to quantify SSTR2 expression. We aimed to validate the DIA also on SSTR5 in a new cohort of GH-secreting pituitary tumors, with immunohistochemistry performed in a different laboratory, and to correlate fg-SRL response with SSTs expression.
View Article and Find Full Text PDFEndocrine
December 2024
Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Purpose: The growth hormone (GH) level on postoperative day one (POD1), i.e., POD1GH, holds significant value in assessing surgical efficacy and predicting long-term remission in patients with acromegaly.
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