bluuebunny/crossref_metadata_2025 huggingface dataset:
THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
Authors: Gray Cater Taylor Lauren , Borges Espinosa Luis
Published: October 2023

Disclosure: T.L. Cater: None. L. Borges Espinosa: None.

Introduction: Familial hyperkalemia and hypertension syndrome or pseudohypoaldosteronism type 2 (PH2) is a rare monogenic hypertension resulting from WNK1, WNK4, KLHL3, or CUL3 gene mutation. Subsequent interference at the Na-Cl co-symporter, epithelial Na, or ROMK channel results in metabolic acidosis, hyperkalemia, and hypertension responsive to thiazide treatment. This case demonstrates PH2 resulting from a KLHL3 gene variant not previously described. Mutations to KLHL3 decrease Na-Cl cotransporter expression in the distal convoluted tubule leading to increased sodium and chloride reabsorption, volume expansion, hypertension, and, therefore, less sodium available for potassium exchange in the collecting duct. Case Description: A 30-year-old female G1P0 with twin gestation was admitted at 33 weeks for preeclampsia with severe features. PMH was unremarkable. She underwent C-section and was discharged home with healthy twin daughters. BMP during admission showed hyperkalemia with peak potassium 5.2 mmol/L which improved to 4.6 mmol/L by discharge. Essential hypertension was diagnosed 3 months later (BP 130/90, 78 bpm, RR 16, BMI 30.0 kg/m2). Labetalol 50 mg BID was initiated. BMP obtained showed hyperkalemia as high as 6.4 mmol/L. Further workup showed undetectable renin with normal aldosterone, hyperchloremic metabolic acidosis with chloride 111 mmol/L and bicarbonate 20 mmol/L, and normal EKG. She was managed in the ED where her potassium improved to 5.1 mmol/L with persistent hyperchloremic metabolic acidosis. A diagnosis of pseudohyperkalemia was presumed initially. Labetalol was discontinued in favor of hydrochlorothiazide 12.5 mg daily. Lost to follow-up, she presented 10 years later to Endocrinology at age 41 for chronic hyperkalemia and hyperchloremic metabolic acidosis. Labs showed potassium 6.5 mmol/L, chloride 108 mmol/L, and bicarbonate 23 mmol/L. Exam showed BP 133/98, BMI 26.63 kg/m2. She recounted several ER visits over the past decade for hyperkalemia with highest reported potassium of 7.8. She had stopped her thiazide due to dizziness, palpitations, and fatigue. Family history was now notable for hyperkalemia in her father, two brothers, and fraternal niece but no genetic testing was available. We resumed hydrochlorothiazide 12.5 mg every other day; follow-up labs showed improved potassium 5.2 mmol/L. Genetic testing revealed heterozygosity in the KLHL3 gene for the c.1064T > G sequence, a variant that has not been reported in the literature or large population database. Conclusion: Hypertension in PH2, distinct in its presentation with hyperkalemia and metabolic acidosis, requires a detailed family history and hormonal evaluation to make the diagnosis. Genetic testing in our case patient revealed a variant at the KLHL3 gene not previously described, underscoring the utility of genetic testing in understanding this rare condition.

Presentation: Thursday, June 15, 2023
FRI088 Vanishing Bile Duct Syndrome?
Authors: Malvar Cyerwin Monique T , Bleich David , Moran Heberth
Published: October 2023

Disclosure: C.T. Malvar: None. D. Bleich: None. H. Moran: None.

Background: Dyslipidemia is a common metabolic disorder in the US, but only a few conditions can cause a total cholesterol greater than 1000 mg/dl. We present a suspected case of vanishing bile duct syndrome in a patient referred to the emergency department due to transaminitis. Case Report: A 41-year-old female with type 2 diabetes mellitus and alcohol use disorder was found to have abnormal liver function tests. She had jaundice, pruritus, and bipedal edema for 2 weeks, but had quit drinking approximately 2 years ago. She denied any recent travel, sick contacts, prior history of hyperlipidemia, family history of premature CAD or lipid abnormalities. On chart review, she received Azithromycin 2 months before presentation for a presumed upper respiratory tract infection. On evaluation, she had scleral icterus and jaundice. Initial labs revealed Na 117 (133 - 145 meq/l), Cl 84 (97 - 110 meq/l), glucose of 542 (70 - 109 mg/dl), total bilirubin 20.9 (<=1.0 mg/dl), 218 (0 - 33 U/L), AST 133 (0 - 32 U/L), GGTP 778 (5 - 36 u/l), Alkaline phosphatase 2,327 (35 - 105 u/l), Lipase 252 (13 - 60 U/L), Total cholesterol 1329 (100 - 200 mg/dl), LDL 1282 (0 - 99 mg/dl), HDL 13, and Triglycerides 172 (0 - 200 mg/dL). Alpha 1 antitrypsin, Liver Kidney Microsomal (LKM-1) Antibody, ANA, Antimitochondrial antibody, Anti-smooth muscle antibody, Ceruloplasmin, CMV, EBV, HSV, and HIV were all within normal limits. An abdominal CT revealed a right pleural effusion and cholelithiasis without gallbladder wall thickening. A right upper quadrant ultrasound demonstrated hepatic steatosis. Magnetic resonance cholangiopancreatography (MRCP) showed no focal lesions, fatty infiltrations, or ductal dilatation. Ursodeoxycholic acid and cholestyramine were started for pruritus. Pseudohyponatremia was due to the increased lipid fraction in blood. Lipoprotein phenotyping revealed type IIb hypercholesterolemia with elevated triglycerides. An apo-lipoprotein B level was 147 mg/dl at the upper limit of normal (range 50-150 mg/dL). Cholestasis-induced hypercholesteremia was considered as a diagnosis. Endoscopy esophageal ultrasound with liver biopsy revealed a smooth liver with non-cirrhotic appearance, severe cholestatic pattern of injury, including bile duct infarcts, and marked bile ductular reaction. Ezetimibe was started instead of a statin due to elevated liver enzymes. Discussion: Vanishing bile duct syndrome is an extremely rare condition unknown to many clinicians. Patients present after drug-induced liver injury. Treatment focuses on symptomatic relief and supportive care. Hyperlipidemia in these patients minimally respond to statins and are thus avoided. The prognosis of these patients can vary from slow recovery to eventual cirrhosis with end-stage liver disease requiring transplant. Increasing awareness among physicians is essential to facilitate its diagnosis and management.

Presentation: Friday, June 16, 2023
FRI095 Pseudo Anion Gap Metabolic Acidosis Secondary To Severe Hypertriglyceridemia
Authors: Connery Grissim C , Ward Samuel , Izuora Kenneth E , Champion Amber
Published: October 2023

Disclosure: G.C. Connery: None. S. Ward: None. K.E. Izuora: None. A. Champion: None.

Background/Objective: Severe hypertriglyceridemia can falsely alter multiple lab parameters due to the high lipid fraction of the blood sample. We present a patient who initially presented with severe metabolic acidosis but proved to have normal pH and bicarbonate after correction for hypertriglyceridemia. Case Report: A 34-year-old female with past medical history of recurrent acute on chronic pancreatitis secondary to hypertriglyceridemia, type 2 diabetes, obesity, and hypertension presented to the emergency department with epigastric pain. The patient was initially diagnosed with acute pancreatitis, diabetic ketoacidosis (DKA), and hyponatremia. Initial labs showed sodium 116 mmol/L, glucose 617 mg/dL, bicarbonate < 5 mmol/L, blood ketones 0.8 mmol/L, lactic acid 2.57 mmol/L, and creatinine 0.95 mg/dL. A venous blood gas (VBG) revealed pH 7.42, pCO2 36 mmHg, pO2 62 mmHg, and bicarbonate 24 mmol/L. Her lipid panel revealed triglyceride levels > 4000 mg/dL. The discrepancy in bicarbonate levels between the blood chemistries and VBG were attributed to a pseudo-anion gap metabolic acidosis secondary to her hypertriglyceridemia. After treatment with insulin infusion, hypertriglyceridemia resolved and her bicarbonate levels on renal function panel normalized. Discussion: The high lipid fraction of blood plasma in patients with severely high triglyceride levels can confound other laboratory parameters. Pseudo hyponatremia secondary to elevated triglycerides is one example of a commonly known lab abnormality. In our patient, her initial bicarbonate levels on renal function panel led to concern for severe metabolic acidosis that was not consistent with her mild blood ketones and lactic acid levels. Further investigation with VBG revealed normal pH and bicarbonate levels. Conclusion: Severe hypertriglyceridemia may significantly alter bicarbonate measurement on blood chemistries. Further investigations with blood gasses should be pursued to confirm these abnormalities when suspected.

Presentation: Friday, June 16, 2023
FRI108 Role Of Obesity In Patients With Coronary Artery Dissection
Authors: Karki Sadichhya , Deenadayalan Vaishali , Shoura Sami , Gajjar Rohan , Shahi Anoj
Published: October 2023

Disclosure: S. Karki: None. V. Deenadayalan: None. S. Shoura: None. R. Gajjar: None. A. Shahi: None.

Background: Coronary artery dissection (CAD) is an established cause of acute coronary syndrome (ACS) in the general population. However, its risk factors and pathophysiology remain poorly understood. We aim to compare the clinical outcomes in patients admitted for CAD with and without obesity. Methods: This was a trend study of the National Inpatient database from 2010 to 2019. Adult patients (age >18) with a principal diagnosis of APE were identified using the International Classification of Diseases code, tenth revision (ICD-10), and were divided into two groups based on a secondary diagnosis of Morbid Obesity (MO). Primary outcomes evaluated were in-patient mortality, Length Of Stay (LOS) and Total Hospitalization Charges (THC). Secondary outcomes included acute severity measures like blood transfusion, Intensive Care Unit (ICU) admission, Cerebrovascular Accidents (CVA), and Acute Kidney Injury (AKI). Multivariate linear and logistic regression were used to adjust for confounders. We estimated trends, inpatient mortality, mean length of hospital stays (LOS) and mean total hospital charges (THC) over the period. Multivariable regression analysis adjusted for age and sex was used to obtain trend statistics on outcomes. Results: Out of 2,440 adult patients admitted with CAD, 440(18%) were found to be obese. The mean age in obese group vs non-obese was 52.8 and 55.9 years respectively. There was a trend towards an increased inpatient mortality among obese patients compared to non-obese with aOR 2.36 (95% CI 0.73-7.59, p=0.148) however, this did not reach statistical significance. Similarly, there was no statistically significant difference in terms of LOS and THC. Among secondary outcomes, the rate of blood transfusion (11.3% vs 4.7%, aOR 1.97, 95% CI 0.77-5.04), AKI (15.9% vs 9.7%, aOR 1.23, 95%CI 0.58-2.65) and CVA (2.2% vs 1.5%, aOR 0.43, 95% CI 0.03-7.58) seemed to be increased in obese group. Odds of ICU admission was similar between both the groups (10.2 % vs 10.5%, aOR 0.75, 95% CI 0.33-1.68). Conclusion: Obesity does not significantly increase the in-patient mortality and other secondary outcomes among patients admitted for CAD which is reassuring. Future studies looking into the pathophysiology behind this phenomenon are needed.

Presentation: Friday, June 16, 2023
FRI109 D-Allulose Inhibits NF-kB- And AP1-Mediated Inflammatory Pathways In HepG2 Cells
Authors: Gupta Nidhi , Batch-Joudi Jennifer , Danielle Graham Lauren , Champagne Kareen , Warda Firas , John Haas Michael , Mooridian Arshag
Published: October 2023

Disclosure: N. Gupta: None. J. Batch-Joudi: None. L.D. Graham: None. K. Champagne: None. F. Warda: None. M.J. Haas: None. A. Mooridian: None. Nothing to Disclose: NG, J B-J, LG, KC, FW, MJH, ADM. Source of Research Support: No outside funding was used for this research.

Rare sugars such as D-allulose and its derivatives are defined as monosaccharides that are rare in nature. D-allulose is an epimer of D-fructose and is used primarily as a non-nutritive sweetener. D-allulose is also a functional food due to its ability to lower fasting plasma glucose and post-prandial glucose levels in both normoglycemic and diabetics, most likely due to its insulin-mimetic properties as well as its ability to enhance glucagon-like peptide 1. D-alluose has also been shown to possess anti-inflammatory and immunosuppressant activity in allogenic orthotopic liver transportation, neutrophil activation, and monocyte chemoattractant protein-1 expression in endothelial cells. We examined the effects of D-allulose on two well characterized pathways that promote inflammation in HepG2 hepatoblastoma cells, specifically nuclear factor κB (NF-κB) and activator protein 1 (AP1). HepG2 cells were exposed to tumor necrosis factor α (TNFα) (10 ng/ml), lipopolysaccharide (LPS) (10 nM), and high dextrose (27.5 mM). Treatment with 0, 2.8, 5.5, 11, 22, and 27.5 mM D-allulose decreased TNFα-dependent NF-κB and AP1 reporter plasmid activity and 2.8- and 5.5-mM D-alluose decreased NF-κB p50 and p65 subunit expression, measured by Western blot. D-allulose treatment increased IκB expression in TNFα treated cells. D-alluose also suppressed c-jun, phospho-c-jun, and c-fos AP1 subunit expression in TNFα treated cells. Similar effects were observed in D-allulose-treated cells (2.8 and 5.5 mM) exposed to high dextrose and LPS. These results suggest that D-allulose mediates some of its anti-inflammatory effects via suppressing NF-κB and AP1 activity.

Presentation: Friday, June 16, 2023
FRI110 Prevalence Of Thromboembolic Events In 51 Patients Treated For Cushing’s Disease With Pituitary Surgery At University Hospital Of Wales Over A 15-year Period
Authors: Raj Suresh John Romesh Paul , Witczak Justyna , Rees Aled , Hayhurst Caroline , Lansdown Andrew
Published: October 2023

Disclosure: R. Suresh John: None. J. Witczak: None. A. Rees: None. C. Hayhurst: None. A. Lansdown: None.

Background: Hypercortisolism is associated with a hypercoagulable state and both arterial and venous thromboembolic events (TE). Aim: To determine the prevalence of TE in our cohort of patients with Cushing’s Disease (CD) undergoing pituitary surgery. Methods: Patients with a clinical & biochemical diagnosis of Cushing’s Disease who had undergone pituitary surgery at University Hospital of Wales between 2007-2022 were identified from a database. Clinical, biochemical and radiological data were studied from the time of diagnosis to the period of 6 months following pituitary surgery. Results: 51 patients were identified: 15 Male, 36 Female, median age 46 (11-77)y. Total group: 5/51 (9.8%) patients had a TE. Pre-surgery: 2/51 (3.9%) had a TE (Deep vein thrombosis (DVT) = 1; Aortic thrombus = 1), both at time of diagnosis. Mean 24-h Urinary Free Cortisol (UFC) was 1126nmol in TE group vs 662nmol in non-TE group (p=0.64) and mean cortisol after overnight dexamethasone suppression test (ODST) was 251nmol/L in the TE group vs 327nmol/L in the non-TE group (p=0.64). Post-surgery: All patients received standard thrombo-prophylaxis with low-molecular weight heparin peri-operatively. 3/51 (5.9%) had TE within 6-months post-surgery (DVT=1, pulmonary embolism (PE)=1, cavernous sinus thrombosis=1), all occurred within 21 days of surgery and none had other risk factors for VTE. Mean time from diagnosis to surgery was 187 days in TE group vs 127 in non-TE group (p=0.43). At diagnosis, mean 24-h UFC was 560nmol in TE group vs 699nmol in non-TE group (p=0.82), mean cortisol after ODST was 420nmol/L in TE group vs 321nmol/L in non-TE group (p=0.46). Mean post-op cortisol was 221nmol/L in TE group vs 257nmol/L in no TE group (p=0.85). No TE events occurred between 22 days-6 months post-surgery. Conclusion: In our cohort, 9.8% patients had a TE event. 3.9% occurred pre-surgery and 5.9% in the early post-operative period, which concurs with data from other studies. There was no correlation with level of hypercortisolism and TE events in our group. Timing, dose & duration of prophylactic anticoagulation in CD patients needs careful consideration.

Presentation: Friday, June 16, 2023
FRI120 Metabolic Profile Of A Young Adult Population Assisted By A Primary Health Care Unit In A Large Urban Center
Authors: Barberá Boghossian Rodney , Campello Lopes Carolina , de Barros Junqueira Livia Lopes Monteiro , Góes Neno João Oliveira , Silva de Almeida Beatriz Câmara , Ferrão Raphaella , Velho Junior Ivan da Costa , Castellões de Rezende Pedro Paulo , da Costa Fernandes Ana Cristina Tenório , Gomes Monteiro Daniela Fiuza
Published: October 2023

Disclosure: R.B. Boghossian: None. C.C. Lopes: None. L.L. Junqueira: None. J.O. Neno: None. B.C. Almeida: None. R. Ferrão: None. I.D. Velho Junior: None. P.C. Rezende: None. A.T. Fernandes: None. D.F. Monteiro: None.

Introduction: Dyslipidemia, Glucose Intolerance (GI), Diabetes Mellitus (DM), and Metabolic Syndrome (MS) are metabolic conditions often asymptomatic and related to high cardiovascular (CV) morbidity and mortality. Nonetheless, these conditions are not commonly screened in younger adults. The LapARC cohort Study is a population-based study to assess CV risk profile in a young adult population. Objective: To evaluate the prevalence of dyslipidemia, DM, GI, and MS in a young adult population enrolled in the Family Health Strategy (FHS) in an urban center. Methods: Cross-sectional population study that enrolled individuals aged 20-50 years registered in an FHS unit. Sociodemographic, anthropometric characteristics, and CV risk factors were recorded. Office blood pressure (BP) was obtained by the average of 2 measurements obtained on two different occasions. All participants underwent laboratory evaluation (lipid and glycemic profile) and home blood pressure monitoring (HBPM). The bivariate analysis compared paciente with and without metabolic alterations. SPSS 19.0 was used in the statistical analysis. Results: We evaluated, up until this moment, 632 individuals [39.6% male gender; average age: 33.6 ± 9 years old]. The most common modifiable CV risk factors were physical inactivity (44.0%), and obesity (26.0%). The prevalence of dyslipidemia was 40%. These individuals were older, more obese and with a bigger association of hypertension and GI. Regarding the glycemic profile, 57 (9%) individuals with GI e 18 (3%) with DM. Diabetic pacientes were older, obese, with a bigger prevalence of hypertension and dyslipidemia while those with GI had just bigger prevalence of dyslipidemia compared to normoglicemic individuals. A total of 74(12%) individuals were diagnosed with MS. These were older, more obese, sedentary, with a bigger prevalence of hypertension, higher office BP and HBPM and higher levels of albuminuria. Conclusion: This young and apparently healthy population has an adverse cardiometabolic profile, indicating the importance of precocious CV risk stratification. Thus, efficient primary preventive strategies can be implemented to reduce the probability of CV disease development in the future.

Presentation: Friday, June 16, 2023
FRI124 Insights From The Incidence Of Primary Aldosteronism In Patients With Hypokalemia (IPAHK+) - Study
Authors: Gruber Sven , Stasi Evangelia , Boan Pion Antonio , Steiner Regula , Sudano Isabella , Beuschlein Felix
Published: October 2023

Disclosure: S. Gruber: None. E. Stasi: None. A. Boan Pion: None. R. Steiner: None. I. Sudano: None. F. Beuschlein: None.

Background: Hypokalemia plays an important role in the diagnosis and management of primary aldosteronism (PA). The hypokalemic variant of the disease accounts for about one third of all cases. However, little is known about the incidence of PA in a hypokalemic population. Design: The IPAHK+ study is an epidemiological, monocentric, cross-sectional trial to provide evidence on the incidence of PA in a hypokalemic outpatient population. Methods: Recruitment of outpatients with hypokalemia ≤3 mmol/l is carried out on a continuous referral-basis through an automated data delivery system at the University Hospital Zurich (USZ). Todate, 69 patients underwent the study protocol, which includes guideline-compliant workup for PA. Results: The mean age of the participants was 52.5±1.5 years with a sex ratio of 35:34 women to men, a mean potassium value of 2.77±0.03 mmol/l [1.8; 3.0] and a prevalence of arterial hypertension of71%. PA was diagnosed in 45.9% of all participants, all of whom had a history of hypertension. The incidence of PA increased continuously with decreasing potassium level with proportions of 26.7%,45.8% and 59.1% in the subgroups of 3.0 mmol/l (n=15), 2.8-2.9 (n=24) and ≤2.7 mmol/l (n=22),respectively. In the subgroup of hypertensives the incidence of PA was as high as 65.1%. Prior testing,60.9% of all patients presented at least with one plausible other cause for their hypokalemia with potential drug triggers accounting for the largest portion (33.3%). Among participants on diuretics the incidence of PA was 57.9%. Conclusions: The incidence of PA in the investigated outpatient population was more than 4 out of 10and inversely correlated with baseline potassium levels. Moderate or severe hypokalemia, regardless of its cause, should therefore prompt evaluation for PA in hypertensive individuals. Normotensive PA was not observed in our cohort. The significance of the study is limited by the still low number of enrolled patients with a potential selection bias.

Presentation: Friday, June 16, 2023
FRI137 Histologic And Genetic Characteristics Of Primary Aldosteronism In Late Adulthood
Authors: Blinder Amy , Nanba Kazutaka , Sapiro Dina , Baker Jessica , Liu Chia-Jen , Bancos Irina , Lyden Melanie , Young William , Wachtel Heather , Cohen Debbie , Luther James , Ann Williams Tracy , Reincke Martin , Else Tobias , Giordano Thomas J , Udager Aaron , Rainey William E
Published: October 2023

Disclosure: A. Blinder: None. K. Nanba: None. D. Sapiro: None. J. Baker: None. C. Liu: None. I. Bancos: None. M. Lyden: None. W. Young: None. H. Wachtel: None. D. Cohen: None. J. Luther: None. T.A. Williams: None. M. Reincke: None. T. Else: None. T.J. Giordano: None. A. Udager: None. W.E. Rainey: None.

Background: There is accumulating evidence that changes in adrenal histology and regulation of renin-angiotensin-aldosterone system occur with age. Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Recent clinical studies suggest unique characteristics of PA in elderly patients, including high prevalence of comorbidities and low clinical cure rate after adrenalectomy. However, histologic and genetic features of PA in late adulthood have not been well elucidated. Objective: To determine histologic and genetic characteristics of PA in late adulthood. Methods: Seventy-six patients who underwent unilateral adrenalectomy at the age of 60 or older were included in this study. Formalin-fixed, paraffin-embedded (FFPE) sections of resected adrenal tissue were used for the analysis. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed to identify the source of inappropriate aldosterone production. Histologic classification was made according to the HISTALDO (histopathology of primary aldosteronism) consensus. CYP11B2 IHC-guided DNA capture followed by sequencing analysis using direct Sanger sequencing or ion torrent based next-generation sequencing (NGS) was performed. Results: Median age of the studied patients was 70 (interquartile range: 64-73). Based on the CYP11B2 IHC, histologic diagnosis was made as follows; aldosterone-producing adenoma (APA, n=23), aldosterone-producing nodule (APN, n=41), and non-functioning adrenocortical adenoma (NFA, n=6). The remaining six cases had multiple CYP11B2-expressing neoplastic lesions, including APA with APN (n=2) and multiple APNs (n=4). Co-existence of NFA with APA or APN(s) was also observed in 13. Sequencing analysis revealed that somatic KCNJ5 mutation was the most frequent genetic alteration in APA (7/23, 30%), whereas somatic CACNA1D mutation was the most common genetic cause of APN (20/39 with successful sequencing, 51%). Of the 18 sequenced NFA DNA samples, two had somatic mutations in CTNNB1 (n=1) and GNAS (n=1). Conclusion: APN is the major histologic feature of PA in late adulthood. Co-existence of NFA also appears to be a frequent observation in this age population. Somatic CACNA1D and KCNJ5 mutations are common in APN and APA, respectively.

Presentation: Friday, June 16, 2023
FRI138 Diagnostic Accuracy Of Plasma Renin Activity Measured By Radioimmunoassay And LC-MS/MS For The Screening Of Primary Aldosteronism
Authors: Hong A Ram , Hee Yoon Jee , Yong Park Ji , Choi Wonsuk , Kyung Kim Hee , Kang Ho-Cheol
Published: October 2023

Disclosure: A. Hong: None. J. Yoon: None. J. Park: None. W. Choi: None. H. Kim: None. H. Kang: None.

Background: Plasma aldosteronism (PA) is screened based on the levels of aldosterone-to-renin ratio (ARR) and/or plasma aldosterone concentration. However, false positive cases are often observed due to low levels of plasma renin activity (PRA). Here, we aimed to compare diagnostic accuracy of PRA measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the screening of PA. Materials and Methods: We retrospectively included 67 patients in whom PRA was measured using both RIA and LC-MS/MS due to adrenal incidentaloma or suspected secondary hypertension in a tertiary referral center. Patients with ARR≥20 underwent saline infusion test (SIT) and/or captopril challenge test (CCT) for the confirmation of PA. Results: The mean PRA was 3.1±7.5 ng/mL/hr by RIA and 3.0±6.3 ng/mL/hr by LC-MS/MS (P=0.284). The mean ARR was 53.7±137.4 by RIA and 41.2±129.9 by LC-MS/MS. The correlation coefficient between RIA and LC-MS/MS was 0.992 in patients with ARR<20 (n=38) (P<0.001) and 0.595 in patients with ARR ≥20 (n=29) (P=0.001). In patients who underwent confirmative test (CCT or SIT), false-positivity rate was 77.8% (7/9) based on RIA and 66.7% (6/9) based on LC-MS/MS. Conclusion: PRA measured using LC-MS/MS showed a significant positive correlation with PRA using RIA, particularly at ARR<20. ARR calculated by both methods for PRA revealed similar false-positives. Further studies are needed to validate diagnostic accuracy between the two methods of PRA for PA screening.

Presentation: Friday, June 16, 2023
FRI139 Identification Of Robust Aldosterone-Producing Adenomas-related Genes Using Adrenal Genome-wide Transcriptome Analysis
Authors: Lee Seunghyun , Lee Taesic , Yoo Gilsung , Soo Lim Jung
Published: October 2023

Disclosure: S. Lee: None. T. Lee: None. G. Yoo: None. J. Lim: None.

Primary aldosteronism (PA), the most common cause of secondary hypertension, is caused by aldosterone overproduction in one or two adrenal glands. It carries a higher risk of cardiovascular disease and mortality compared to essential hypertension. In an effort to identify the underlying molecular mechanisms regarding aldosterone secretion and cell proliferation in aldosterone-producing adenomas (APA), genome-wide transcriptome analyses have been conducted; however, there are still some limitations that need to be addressed since a relatively small number of samples were analyzed at a single center in most studies. In this study, we performed integrative and systematic analysis using adrenal transcriptome datasets to verify candidate genes robustly associated with APA and obtain more generalized signatures involved in the pathophysiology of PA. Three mRNA datasets for adrenal tissues (GSE8514, GSE60042, and GSE64957) were obtained from the Gene Expression Omnibus Database. For the first two datasets, normal adrenal samples from patients with renal cell carcinoma and adrenal tissue samples adjacent to APA were included as controls, respectively. In GSE64957, zona glomerulosa (ZG) and zona fasciculata (ZF) samples were analyzed separately in the current study (GSE64957ZG and GSE64957ZF). Differentially expressed gene (DEG) investigation and comparative analysis were conducted using the limma method. The selection criteria for APA-related genes were as follows: those that are significantly dysregulated in more than three of the four datasets and show a consistent trend of up- or down-regulation in four datasets. 5,375 genes were present in all transcriptome datasets; for the GSE64957ZG, 57 DEGs were identified in the APA group, among which 14, 7, and 37 genes were also dysregulated in the APA group of GSE64957ZF, GSE8514, and GSE60042, respectively. All comparisons among four lists of DEGs exhibited significant enrichment results. The highest degree of overlap was shown in the DEG pair of GSE64957ZG-GSE60042. As a result, approximately 20 genes (12 upregulated and 12 downregulated DEGs), including CYP11B2, PCP4, and ATP2A3, were selected as the final APA-related genes. This study demonstrated several candidate genes that are strongly relevant to APA by examining whole genome disease-related signatures. Besides CYP11B2, it seems that alteration in PCP4 and ATP2A3 genes would be much more involved in the pathogenesis of PA, which warrants further investigation along with validation for the role of the remaining genes.

Presentation: Friday, June 16, 2023
FRI154 Saline Suppression Testing And Acute Hypocalcemia: Impacts On Diagnostic Testing For Primary Aldosteronism
Authors: Warachit Parksook Wasita , Michelle Brown Jenifer , Milks Julia , Moore Anna , Niebuhr Yvonne , Honzel Brooke , Vaidya Anand
Published: October 2023

Disclosure: W.W. Parksook: None. J.M. Brown: Consulting Fee; Self; Bayer, Inc. J. Milks: None. A. Moore: None. Y. Niebuhr: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; HRA Pharmaceuticals, Mineralys.

Background: Calcium ion signaling is a critical factor required for the physiologic production of aldosterone. Emerging evidence has revealed that the majority of cases of primary aldosteronism involve pathogenic somatic mutations that ultimately increase calcium signaling and autonomous aldosterone production. Therefore, testing for primary aldosteronism that modulates calcium homeostasis may influence the diagnostic interpretation of the results. Method: Overweight to obese participants with metabolic risk factors and pre-hypertension or stage 1 hypertension (n=56) underwent a standard seated saline suppression test (SSST). Measurement of blood pressure, plasma aldosterone, serum calcium, as well as other factors, was performed at times 0, 120, and 240 minutes during SSST. Linear regression models were used to analyze the association between changes in calcium and each parameter. Results: Following 2 liters of saline infusion during SSST, all 56 participants (100%) had a significant decrease in serum calcium levels from baseline, with 26 (47%) developing new-onset frank hypocalcemia (calcium <8.6 mg/dL). The mean baseline serum calcium was 9.2 ± 0.3 mg/dL, which declined to 8.9 ± 0.4 mg/dL at 120 mins (P<0.001), and to 8.6 ± 0.4 mg/dl (P<0.001) at 240 mins when the SSST concluded. Consistent with the known vasopressor effect of calcium, greater drops in serum calcium levels were associated with lower blood pressure at 240 minutes (β;= 13.5, P<0.01 for DBP; β;= 10.7, P= 0.06 for SBP). Among those with post-SSST aldosterone levels <10 ng/dl (a categorical threshold used to exclude primary aldosteronism), greater reductions in serum calcium levels were associated with larger drops in aldosterone levels (β;= 9.9, P<0.05). Conclusion: The standard SSST induced a substantial decline in serum calcium levels in 100% of participants, with nearly half of all participants developing frank hypocalcemia at the end of saline infusion. Since calcium is known to play a critical role in physiologic and pathophysiologic production of aldosterone, these findings raise the question whether hypocalcemia induced by the acute loading of 2 liters of saline may confound the interpretation of aldosterone changes. Further research should focus on better understanding the diagnostic implications of these results and potential limitations of the SSST to exclude primary aldosteronism.

Presentation: Friday, June 16, 2023
THU006 Exploring Primary Care Resident Perspectives On Diabetes Education In Training
Authors: Francis Nnenia , Cardillo Serena , Nandiwada Deepa R
Published: October 2023

Disclosure: N. Francis: None. S. Cardillo: None. D.R. Nandiwada: None.

Background: The training residents gain in Family Medicine (FM) and Internal Medicine (IM) residency programs provide a critical foundation for their knowledge in diabetes (DM) management. It is one of the most common diagnoses physicians-in-training will encounter in their residency training programs and in clinical settings. However, a 2012 study compared diabetes care in resident clinics versus private physicians and found significant decrease in patient satisfaction (56.5% vs. 71.3%) in resident clinics. A 2020 study surveying primary care (PC) residency program directors showed that most FM and IM residency training programs focus on the core diabetes care and management topics with much less focus on emerging topics, such as 2nd generation insulin analogs and digital health technologies. The purpose of our survey was to better assess current resident perceptions and attitudes towards their DM education and their perceived comfort level in comprehensive DM counseling, evaluation, and management. Methods: A 12 item survey was designed using the Qualtrics program. The survey link was sent via email to IM- PC and FM residents at a major academic medical center. Data was collected from September 13th, 2022 to present. The survey included a combination of multiple choice, Likert scale and ranking questions. Results: 14 residents responded to the survey to date with the majority (71%) belonging to the IM-PC group and the remainder (29%) family medicine. Residents felt most comfortable managing diabetes related complications and counseling on foot and eye care and hypoglycemia. Respondents reported being most uncomfortable in prescribing non-insulin medication (50%) and initiating an insulin regimen (43%) and less comfortable counseling patients on continuous glucose monitoring systems (83%) and insulin administration (66%). While majority of residents (72%) found their DM curriculum clinically relevant, 85% of residents reported there was not enough time allotted. Respondents felt a more longitudinal lecture series, with increased access to treatment frameworks and on-site feedback on their DM counseling and care would best supplement their DM curriculum. Conclusion: This survey data explores specific areas that residents have identified as being least comfortable and also expresses what they identified as the most preferable ways to modify and design an educational intervention. This information allows for tailored curricular intervention highlighting diabetes technologies, insulin and non-insulin prescribing practice in a longitudinal lecture style format that provides access to DM treatment frameworks and incorporates direct on-site feedback to the residents. This provides evidence for the development of a novel clinically integrated DM curriculum.

Presentation: Thursday, June 15, 2023
THU248 Screening For Heart Failure In Patients With Diabetes Mellitus - A SwissDiab Study
Authors: Brandle Michael , Knaus Laura , Quarella Marino , Maeder Micha , Buser Marc , Renstrom Frida
Published: October 2023

Disclosure: M. Brandle: None. L. Knaus: None. M. Quarella: None. M. Maeder: None. M. Buser: None. F. Renstrom: None.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to significantly reduce the risk of hospitalization for heart failure (HF) and death from cardiovascular causes in patients with diabetes and HF. Since the diagnosis of HF is challenging, the condition often remains undetected, and the prevalence in diabetes patients is unclear. The aim of this study was to evaluate the prevalence of HF in patients with diabetes enrolled in the Swiss Diabetes Registry (SwissDiab) and the proportion prescribed SGLT2i, to help to determine the need to reinforce clinical treatment guidelines and establish regular screening of HF.SwissDiab is a multicenter longitudinal observational study of outpatients with diabetes in tertiary care. The current study was conducted at the Cantonal Hospital of St.Gallen, Switzerland. All patients with a SwissDiab study visit between 28.09.2020 and 31.03.2022 were screened for HF according to a standardized protocol based on the diagnostic algorithm established by the European Society of Cardiology. Patients with ≥1 risk factor and/or symptoms of HF and a NT-proBNP ≥125 ng/L were referred to the Division of Cardiology for echocardiography and a clinical evaluation of HF, further stratified by HFpEF, HFmrEF, and HFrEF. The study was approved by the regional Ethics Committee East Switzerland (EKOS, PB_2016-01449) and all SwissDiab participants provided written informed consent. Out of 555 patients with diabetes, 530 had data available for analysis: 168 with type 1 diabetes (T1DM); 315 with type 2 diabetes (T2DM), and 47 with other forms of diabetes n=47. The median (IQR) age was 60.9 (49.0-69.0) years, n=162 (30.6%) were females, diabetes duration 14.0 (8.0-21.0) years, HbA1c 7.1 (6.6-7.8)%, low-density lipoprotein cholesterol 2.6 (2.1-3.2) mmol/L, and n=114 (21.5%) were current smokers. In total, HF was present in n=59 (11.1%) (T1DM, n=4 [2.4%]; T2DM, n=50 [15.9%]; other, n=5 [10.6%]) of which 35 (59.3%) were newly diagnosed. 34 of 59 patients presented with HFpEF (57.6%), 7 with HFmrEF (11.9%), and 18 with HFrEF (30.5%). Of the 59 patients with HF, n=19 (32.2%) were prescribed SGLT2i (HFpEF, n=7 [36.8%]; HFmrEF, n=2 [10.5%]; HFrEF, n=10 [52.6%]). Of the 24 patients with a previously known diagnosis of HF, 50% were treated with SGLT2i (2 out of 3 patients with HFmrEF and 10 out of 15 patients with HFrEF). All of the patients with HF that were treated with SGLT2i had T2D.The results indicate that roughly one in ten patients enrolled in SwissDiab have HF, and one in six patients with T2D. Patients with HFrEF (around 30% of cases) primarily have T2D, of which >50% were prescribed SGLT2i, as compared to 32% overall.

Presentation: Thursday, June 15, 2023
THU257 Retrospective Analysis Of Hemoglobin A1c Utility At A SafetyNet County Hospital
Authors: Joseph Jonathan , Hashim Ibrahim A
Published: October 2023

Disclosure: J. Joseph: None. I.A. Hashim: None.

Background: Diabetes remains a prevalent chronic health condition. Measurement of glycated hemoglobin (A1c) is central to both diagnosis and to monitoring response to therapy and hence the extent of diabetes control. Use of A1c continues to increase in compliance with recommendations by the American Diabetes Association. The utility of A1c measurement at a large SafetyNet county hospital was assessed. In this analysis, our goal is to help guide utilization of A1c testing. Method: All A1c values performed over a period of 14 months between January 2021 to March 2022 were retrieved from the electronic health records system (Beaker, EPIC®). Statical analysis of all A1c data were performed using Excel Microsoft® and NCSS statistical software. A1c data were analyzed for prevalence of abnormalities (>6.5%). Results: A total of 28,760 A1c measurements were performed during the study period. Overall values ranged from 0.06% to >17.6% (Median 6.1%). Patients with A1c <5.7% (n=9535) representing 33% of tested patients. Patients with A1c values between 5.7% and 6.5% (n=7619) representing 26% of patients. Patients with A1c values between 6.5% and 11.0% (n = 10,001) representing 35% of patients. Patient in control with A1c values between 6.5% and 7.5% (n=1350) represented 35.8% of the diabetic population. Those poorly controlled A1c >9% (n=734) represented 19.4% of patients. The remaining patients (n=1605) representing 6% of patients had A1c values >11%. Conclusion: A1c testing is widely practiced with 35 % of patients being diabetic. A1c measurement identified 26% of patients in the pre-diabetic stage and that 33% were non-diabetic. The high HbA1c among some patients indicate a need for more proactive approach to their management. The high percentage of the measured population had A1c below 5.7% and thus raises the question of whether routine screening of A1c is cost-effective. Additional analysis for diabetic patients for degree of control and for assessment of urinary albumin levels is required.

Presentation: Thursday, June 15, 2023
THU266 Lowered HbA1c In Individuals With Long-term Type 1 Diabetes Undergoing BCG Bladder Cancer Therapy
Authors: Dias Hans , Kühtreiber Willem , Faustman Denise L
Published: October 2023

Disclosure: H. Dias: None. W. Kühtreiber: None. D.L. Faustman: None.

Originally developed for the prevention of tuberculosis, the bacillus Calmette-Guérin (BCG) vaccine has shown benefit in diverse human diseases, including infection resistance, allergies, multiple sclerosis and autoimmune diabetes. BCG has also been approved in the United States and Europe since 1972 for early-stage bladder cancer, where it is administered commonly as 6 doses via intravesical therapy for 6 weeks (“high-dose intravesical BCG”). We analyzed three large databases-the Management Science Associates database (with Quest Diagnostics data) (N=263 million adults), the Research Patient Data Registry (RPDR) from the Massachusetts General Brigham (MGB) system (N=6.5 million), and data from Optum Labs (OL)(N=45 million) -for a correlation between high-dose intravesical BCG and HbA1c levels in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). We identified subjects with documented T1D (N=19) or T2D (N=106) undergoing BCG therapy for bladder cancer, and then retrospectively assessed BCG’s subsequent year-by-year impact on blood sugar trends. T1D records were identified by searching for T1D diagnosis and insulin usage; records showing any history of oral hypoglycemic agents (e.g., metformin) were excluded. T2D records were searched for using T2D diagnosis and exclusion of any T1D diagnosis. No patients had a history of BCG treatment/vaccination other than for bladder cancer. Patients with T1D in the datasets showed downward trends in HbA1c values after high-dose intravesical BCG, but not patients with T2D. The data suggests that high-dose intravesical BCG therapy may contribute towards a drop in HbA1c values in T1D, but not T2D. This is consistent with earlier interventional trials of the BCG vaccine in longstanding T1D.

Presentation: Thursday, June 15, 2023
THU282 Improved Fournier’s Gangrene Outcomes With Prior SGLT2i Or Metformin Usage
Authors: Venugopal Sharini , Patel Suraj , Wu Zhengbo , Galbiati Francesca , Oh Jessica , Manroa Pooja , Morariu Elena , Stefanovic-Racic Maja
Published: October 2023

Disclosure: S. Venugopal: None. S. Patel: None. Z. Wu: None. F. Galbiati: None. J. Oh: None. P. Manroa: None. E. Morariu: None. M. Stefanovic-Racic: None.

Introduction: Fournier’s gangrene (FG) is a rare, necrotizing fasciitis of the external genitalia with high mortality up to 30% that is more prevalent in males, diabetes, HIV, and immunocompromised states. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been linked with FG. Interestingly, multiple studies have found no significantly increased risk of FG with SGLT2i use. However, these studies have very large confidence intervals due to the rarity of the observed event. Methods: A retrospective study between 3/1/2013-6/12/2020 was performed at four different tertiary hospitals within the University of Pittsburgh Medical Center (UPMC) system to compare the severity and outcome of FG between type 2 diabetes patients who were treated with SGLT2is, metformin, and insulin prior to admission. Results: 202 patients were admitted for FG (8 on SGLT2is, 80 on Metformin, and 88 on insulin). Baseline characteristics such as age, sex, and HbA1c were generally similar. Duration of diabetes was longer in subjects on insulin vs not on insulin (p<0.001). Creatinine(Cr) on admission was lower in SGLT2i vs not on SGLT2i (p=0.056) and metformin vs not on metformin (p=0.037), but was higher in the insulin vs non-insulin group (p=0.004). The SGLT2i group had a shorter hospital stay (p=0.045), a lower rate of ICU admission (p=0.0093), and a trend toward a shorter ICU stay than the non-SGLT2i group (p=0.053). In the metformin group, the cases of amputation were lower compared to the non-metformin group (p=0.026). In the insulin group, there was a trend toward a longer hospital stay (p=0.057) and ICU stay (p=0.052) vs the non-insulin group. Conclusion: The use of SGLT2i does not appear to worsen the clinical course or outcome of FG and may actually improve it based on our data showing decreased ICU admissions and length of stay. Metformin usage may dampen the severity of FG by significantly decreasing cases of amputation. Noteworthy is that Cr was lower in the SGLT2i and metformin groups. Further analysis of baseline characteristics such as renal function, HbA1c, and duration of diabetes will determine whether they may affect the severity of FG.

Presentation: Thursday, June 15, 2023
THU286 Role Of Carb Counting For Glycemic Control In People With Type 1 Diabetes During The Month Of Ramadan
Authors: Naseem Raheela
Published: October 2023

Disclosure: R. Naseem: None.

AbstractTitle: Role of carb counting for glycemic control in people with type 1 diabetes during the month of RamadanPresenting Author: Raheela NaseemCo-authors: Rabia Imtiaz, Musarrat Riaz, Muhammad Yakoob AhmedaniBackground: Carbohydrate counting is a part of meal planning for individuals with type 1 diabetes (T1D), although not widely used in Asian countries like Pakistan.Aim: To evaluate the effect of carbohydrate counting in individuals with type 1 diabetes mellitus who intended to fast during the month of Ramadan.Methodology: This prospective case-control study was conducted in the Diet& Education Department of Baqai Institute of Diabetology and Endocrinology from April to May 2021. Thirty already registered individuals with T1D, aged ≥ 15 years (who intended to fast), were equally divided into case and control groups. The control group was educated on Ramadan-specific management and a T1D general diet plan, followed by the advised insulin regimen protocol. The case group attended carbohydrate counting sessions for better glycemic control and was provided with the book “Matching Carbs with Insulin” for insulin dosage guidance for different daily meals. A 24/7 telephonic support was provided, along with individual WhatsApp groups; managed by a clinical dietitian and a trained diabetes educator, under the supervision of their physicians. Results: A total of 25 individuals (5 being drop out) with a mean age of 22.56±6.5 years participated. A significant mean glucose level before iftar was found in the case and control groups as 149.78±41.4 mg/dl and 206.05 ± 65.43 mg/dl, respectively. Whereas, the mean glucose levels for non-fasting hours were also significant at 158.45±25.31 mg/dl (case) and 194.87±54.23 mg/dl (control). Overall, 257 episodes of hyperglycemia in the control group while, only 177 in the case group were observed. No hospitalization was needed in both groups. Conclusion: By implementing the carbohydrate counting method, safe fasting was feasible with significant improvement in overall glycemic control without significant major complications.

Table 1. Baseline characteristics of subjects

Table 2. Comparison of SMBGs at different timings

Fig. 1- Mean self-monitoring of blood glucose (SMBG) profile of people with type 1 diabetes

Fig. 2- Frequency of hyperglycemia

Presentation: Thursday, June 15, 2023