Abstract Disclosure: M. Godlewska: None. A. Boguslawska: None. A. Grochowska: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None. Introduction: Clinical, pathophysiological and prognostic significance of different patterns of growth hormone response in oral glucose tolerance test (OGTT) has been recently a focus of extensive debate. Material and Methods We analyzed 116 consecutive patients with newly diagnosed acromegaly between 2012 and 2022. Finally, 89 patients with an MRI-confirmed pituitary tumor, available results of at least 3 GH values in the OGTT before implementation of any treatment were included. Paradoxical rise of GH in OGTT (PR) was defined as an increase of at least 25% of GH at any time point of OGTT compared to baseline GH concentration. Patients were divided into two groups: with PR (PRpos), without PR (PR neg). Among clinical data, baseline GH, IGF-1 and PRL concentrations (expressed as IGF-1/ULN and PRL/ULN ratios), function of pituitary axes were assessed. Tumor largest diameter, tumor volume, cavernous sinus invasion, compression of the optic chiasm, tumor infarction as well as Signal Intensity Ratio (SIR) of the solid part of the tumor and the grey matter of the temporal lobe were assessed. Response to presurgical somatostatin analogues (SSA)(defined as normalization of IGF-1 and ULN ratio) was assessed in 69 patients. Postsurgical remission was defined as GH suppression <1 ug/ml in OGTT and IGF-1/ULN <1. This study was approved by the local Bioethics Committee (1072.6120.72.2020) and is part of statutory research of the Jagiellonian University Medical College (N41/DBS/000407). Results: PR was observed in 34.8% cases. Female/Male ratio was 32/26 for PRneg and 18/13 for PRpos. Median age upon diagnosis was 40,5 years (33.5-58.0) for PRneg and 51.0 (41.0-61.0) for PRpos (p=0.127). Median diagnostic delay was 4 years (IQR 5) for PRneg and 6.5 years (IQR 7) for PRpos (p=0.05). The frequency of hyperprolactinemia, secondary hypogonadism, secondary hypothyroidism did not differ among groups. Nor any differences in nadir GH concentration in the OGTT, glucose levels in 0, 60, 120 min, PRL and IGF-1 concentrations were found. Median fasting GH concentration was significantly higher in PRneg than in PRpos (10.23 ug/ml, IQR 14.19 vs 7.46 ug/ml, IQR 7.96, respectively; p=0.011). Tumor largest diameter and tumor volume, presence of cavernous sinus invasion, compression of the optic chiasm or radiological signs of tumor infarction and SIR did not differ between groups. The frequency of biochemical control after SSA was 31.6% in PRneg vs 42.9% in PRpos; (p=0.386). After surgery, biochemical cure was confirmed in 59.6% of PRneg and 70.8% of PRpos (p=0.352). Conclusions: In our study, patients in PRneg did not differ from PRpos, especially in terms of tumor intensity and response to preoperative medical treatment, as reported previously. PRpos patients had significantly lower baseline GH concentrations than PRneg. However, further evaluation is required to understand the significance of PR. Presentation: Thursday, June 15, 2023