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SUN-176 A Case of Aldosterone-Producing Adenoma with Preoperative Use of a Novel Mineralocorticoid Receptor Antagonist Esaxerenone

Abstract Background: Esaxerenone is a novel mineralocorticoid receptor antagonist (MRA) with nonsteroidal structure and high selectivity to MR, which became clinically available in Japan in 2019. Clinical Case: A 57-year-old woman showed a left adrenal incidentaloma (15mm) on MRI. Serological tests confirmed a diagnosis of primary aldosteronism: baseline plasma aldosterone concentration (PAC) was elevated (47.3 ng/dL, n < 15.9 ng/dL), and plasma renin activity (PRA) below sensitivity. PAC after saline infusion was 43.2 ng/dL. Overnight 1mg dexamethasone suppression test was negative. Her blood pressure had been well-controlled with amlodipine 5mg daily. Despite of large amount of potassium supplementation (96 mmol/day orally and 50 mmol/day intravenously), the level of serum potassium remained low (3.2 mmol/L). Adrenal venous sampling (AVS) was performed successfully, showing laterality index of 45.8 on left. Segmental AVS supported aldosterone hypersecretion from the tumor. After diagnosis, esaxerenone was introduced and the patient became normokalemic without potassium supplementation after a week. No adverse effect occurred in a period of two months before surgery. She underwent laparoscopic left total adrenalectomy. The tumor was positive for CYP11B2, consistent with aldosterone producing adenoma (APA). She became normotensive and normokalemic without any medications. Conclusion: This case illustrates the preoperative effectiveness of esaxerenone on blood pressure and hypokalemia in patients with APA. Key words: Esaxerenone; mineralocorticoid receptor antagonist; case report; adrenal venous sampling; primary aldosteronism; aldosterone producing adenoma

hospitals has not been reported until now. The key challenges in Indian Rural healthcare sector are Lack of Quality Infrastructure, Dearth of qualified medical functionaries and NonAccess to basic medicines and medical facilities thwarts its reach to population in rural India. Indian Health Care sector is a self-pay market. Lack of awareness & affordability being a challenge with patients they remain apprehensive in acceptance of Advanced Technology or newer Techniques. This series is an attempt to study A shift in acceptance of progressive surgeries using Advanced

SUN-054
Background: Genome-wide association studies (GWAS) have identified thousands of common genetic variants associated with human height, implicating hundreds of genes and loci. However, the mechanisms by which many of these genetic variants contribute to human adult height are still unknown. Integrating knowledge of the interaction between genetic background and protein levels in childhood can provide insights into the biology of human growth. Objective: To investigate biological associations at heightassociated loci in the GH-IGF signaling pathway. Methods: We used data from the Cincinnati Genomic Control Cohort, a community-based cohort comprised of 1,020 children. The study was approved by the institutional review board at Cincinnati Children's Hospital Medical Center. Protein levels for free and total IGF-I, intact and total IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 were measured by ELISA in 839 children (ages 3-18 years) and corrected for ageand sex-effects. We associated protein-level phenotypes using plink qassoc and stratified by sex and population, in ~870 European-and African-descent individuals. Metaanalyses were performed using the METAL fixed-effects model. GWAS of anthropometric traits were performed in the UK Biobank of ~400,000 individuals using Bolt-LMM, or curated from publicly available summary statistics. Results: We identified 17 independent genome-wide significant protein-level-associated loci (p<5x10 -8 ). The most robust associations were previously identified expression quantitative trait loci (eQTLs). The IGFBP3 locus was associated with serum total IGFBP3 and IGF-II levels. Despite falling within a height locus, conditional analyses showed that the effect on IGFBP-3 protein levels was independent of the height signal (p=2.8e-31, post conditioning). However, conditional analyses showed that the protein level signal colocalizes with a known GWAS signal for sitting height ratio (SHR). The IGFBP5 locus was associated with IGFBP-5 protein levels and was also independent of height signals identified in the region (p=3.3e-32, post conditioning). Conclusions: We have identified novel pQTLs for IGF2, IGFBP3, and IGFBP5 that act independently from genetic signals in the same regions associated with adult height but may interact with related anthropometric traits including SHR. Additionally, this suggests that SNPs affecting adult height in these loci do not work via increasing serum levels of these proteins but rather through a different and undetermined mechanism.

A Case of Aldosterone-Producing Adenoma with Preoperative Use of a Novel Mineralocorticoid Receptor Antagonist Esaxerenone
Hiroaki Yamanami, MD. TOHOKU UNIVERSITY, Sendai, Japan.

SUN-176
A case of aldosterone-producing adenoma with preoperative use of a novel mineralocorticoid receptor antagonist esaxerenone Background: Esaxerenone is a novel mineralocorticoid receptor antagonist (MRA) with nonsteroidal structure and doi: 10.1210/jendso/bvaa046 | Journal of the Endocrine Society | A927 A927 JESOCI, Volume 4, Abstract Supplement, 2020 high selectivity to MR, which became clinically available in Japan in 2019. Clinical Case: A 57-year-old woman showed a left adrenal incidentaloma (15mm) on MRI. Serological tests confirmed a diagnosis of primary aldosteronism: baseline plasma aldosterone concentration (PAC) was elevated (47.3 ng/dL, n < 15.9 ng/dL), and plasma renin activity (PRA) below sensitivity. PAC after saline infusion was 43.2 ng/dL. Overnight 1mg dexamethasone suppression test was negative. Her blood pressure had been well-controlled with amlodipine 5mg daily. Despite of large amount of potassium supplementation (96 mmol/day orally and 50 mmol/day intravenously), the level of serum potassium remained low (3.2 mmol/L). Adrenal venous sampling (AVS) was performed successfully, showing laterality index of 45.8 on left. Segmental AVS supported aldosterone hypersecretion from the tumor. After diagnosis, esaxerenone was introduced and the patient became normokalemic without potassium supplementation after a week. No adverse effect occurred in a period of two months before surgery. She underwent laparoscopic left total adrenalectomy. The tumor was positive for CYP11B2, consistent with aldosterone producing adenoma (APA). She became normotensive and normokalemic without any medications. Conclusion: This case illustrates the preoperative effectiveness of esaxerenone on blood pressure and hypokalemia in patients with APA. Key words: Esaxerenone; mineralocorticoid receptor antagonist; case report; adrenal venous sampling; primary aldosteronism; aldosterone producing adenoma

SUN-136
Introduction: management of malignant insulinoma is challenging due to the need to control both hypoglycemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study: to analyze clinical-pathological characteristics, treatment modalities and prognosis of patients with malignant insulinoma.

Materials and methods:
Multicenter retrospective study on 31 patients (M 61.3%) diagnosed between 1988 and 2017. Results: The mean age at diagnosis was 48 ± 15 years. In 5 cases (16.1%) the hypoglycemic syndrome occurred after 46 ± 35 months from the diagnosis of NET, in 26 (83.9%) cases it led to the diagnosis of NET, of which 11 cases (42.3%) with mean diagnostic delay of 32.7 ± 39.8 months. The majority of the NET were G2 (70.8 %) and in the pancreatic body-tail (78.6%). The mean NET diameter was 41 ± 31 mm. Metastases were widespread in 40.7%, only hepatic in 37%, only lymph nodal in 18.5%..Surgical treatment was performed in 21/31 (67.7%) with hypoglycemic control in 42.9%. Except for 2 patients with curative surgery, the others underwent further different lines of therapies including somatostatin analogues (SA), Peptide Receptor Radionuclide Therapy (PRRT), everolimus, chemotherapy, TAE/TACE/RFA, radiotherapy. PRRT was performed in 14/31 (45.1%) with complete (42.9 %) or partial (50%) syndrome control. The median follow-up was 60 months. The 5-year survival rate was 62%. The median overall survival (OS) was 40 months. No significant difference in OS was observed according to the site of primary tumour and its dimension. A trend towards increased survival was found according to grading (5-year OS 100% for G1, 77% for G2, 33% for G3). Patients with Ki-67 ≤ 10% had a significant higher survival rate compared to patient with Ki-67 >10% (5-year OS rate 87% vs 43%, p: 0.03). As regards the type of treatment, patients who underwent surgery had a higher survival rate than those who did not (5-year OS 76% vs 31.7%, p= 0.006). Moreover, patients receiving PRRT as II line treatment had a better prognosis than those who underwent it in further lines, although the 5-year OS was not significantly different (80% vs 25% respectively, p=0.057). Conclusions: Our study includes the largest series of patients with malignant insulinomas up to now reported. The hypoglycemic syndrome may occur after years in initially non-functioning NETs, or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 <10% are prognostic factors associated with better survival. PPRT seems to be promising in the control of hypoglycemic syndrome.