TY - JOUR
T1 - Resistance to Somatostatin Analogs in Italian Acromegaly Patients: The MISS Study
AU - Berton, Alessandro Maria
AU - Prencipe, Nunzia
AU - Bertero, Luca
AU - Baldi, Marco
AU - Bima, Chiara
AU - Corsico, Marina
AU - Bianchi, Antonio
AU - Mantovani, Giovanna
AU - Ferraù, Francesco
AU - Sartorato, Paola
AU - Gagliardi, Irene
AU - Ghigo, Ezio
AU - Grottoli, Silvia
PY - 2022
Y1 - 2022
N2 - Approximately 60% of acromegaly patients are not adequately controlled by first-generation somatostatin receptor ligands. This multicenter retrospective study aimed to identify the most relevant biomarkers specific for the Italian acromegaly population. Resistant patients were enrolled consecutively based on time of neurosurgery, while responders were collected in a 1:2 ratio. Clinical characteristics and T2-intensity on MRI scans at diagnosis were retrospectively re-evaluated. Histological analyses of CAM5.2 granulation patterns and SSTR2 expression were centrally performed. Sixty-three resistant patients and thirty-three responders were enrolled. A low-grade SSTR2 expression was the most relevant predictor of resistance identified (OR 4.58, p = 0.013), even considering CAM5.2 immunohistochemistry (OR 2.65, p = 0.047). T2-iso/hyperintense pattern on MRI was also associated with a 3.3-fold greater probability of poor response to medical treatment (p = 0.027), as well as a young age at diagnosis (OR 0.96, p = 0.035). In those patients treated only after neurosurgery due to persistent GH-hypersecretion (51, 53.1%) the absence of any appreciable adenomatous remnant on postoperative MRI was associated with a negligible risk of resistance (OR 0.04, p = 0.003). In the Italian acromegaly population, a low-grade SSTR2 expression seems to be the most relevant predictor of resistance to first-generation somatostatin receptor ligands, followed by a SG/intermediate cytokeratin pattern and a T2-iso/hyperintense MRI signal.
AB - Approximately 60% of acromegaly patients are not adequately controlled by first-generation somatostatin receptor ligands. This multicenter retrospective study aimed to identify the most relevant biomarkers specific for the Italian acromegaly population. Resistant patients were enrolled consecutively based on time of neurosurgery, while responders were collected in a 1:2 ratio. Clinical characteristics and T2-intensity on MRI scans at diagnosis were retrospectively re-evaluated. Histological analyses of CAM5.2 granulation patterns and SSTR2 expression were centrally performed. Sixty-three resistant patients and thirty-three responders were enrolled. A low-grade SSTR2 expression was the most relevant predictor of resistance identified (OR 4.58, p = 0.013), even considering CAM5.2 immunohistochemistry (OR 2.65, p = 0.047). T2-iso/hyperintense pattern on MRI was also associated with a 3.3-fold greater probability of poor response to medical treatment (p = 0.027), as well as a young age at diagnosis (OR 0.96, p = 0.035). In those patients treated only after neurosurgery due to persistent GH-hypersecretion (51, 53.1%) the absence of any appreciable adenomatous remnant on postoperative MRI was associated with a negligible risk of resistance (OR 0.04, p = 0.003). In the Italian acromegaly population, a low-grade SSTR2 expression seems to be the most relevant predictor of resistance to first-generation somatostatin receptor ligands, followed by a SG/intermediate cytokeratin pattern and a T2-iso/hyperintense MRI signal.
KW - CAM5.2 granulation pattern
KW - SSTR2
KW - precision medicine
KW - growth hormone-secreting adenoma
KW - magnetic resonance imaging
KW - first-generation somatostatin receptor ligands
KW - CAM5.2 granulation pattern
KW - SSTR2
KW - precision medicine
KW - growth hormone-secreting adenoma
KW - magnetic resonance imaging
KW - first-generation somatostatin receptor ligands
UR - http://hdl.handle.net/10807/305439
U2 - 10.3390/jcm12010025
DO - 10.3390/jcm12010025
M3 - Article
SN - 2077-0383
VL - 12
SP - N/A-N/A
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
ER -