bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT247 CODE STEMI Due To Excessive Ingestion Of TUMS
Authors: Hershkop Eliyakim
Published: October 2023

Disclosure: E. Hershkop: None.

Hypercalcemia is defined as a serum calcium greater than 10.5mg/dL. It is most commonly caused by malignancy or hyperparathyroidism; a less common cause is excess calcium ingestion, referred to as Milk Alkali Syndrome (MAS). Severe hypercalcemia can lead to renal failure, arrhythmias, and coma. A rare EKG finding is ST elevation mimicking an acute ST Elevation Myocardial Infarction (STEMI). We describe a case of severe hypercalcemia caused by excessive ingestion of TUMS antacids that presented as diffuse ST elevations on EKG which were mistaken for an acute MI. To our knowledge, this is the first case in the literature describing hypercalcemia with ST elevations caused by excessive TUMS ingestion. Case: A 74 year old male with a history of diabetes, hypertension, stroke, and acid reflux presented for recurrent falls due to leg weakness. He endorsed constipation with bowel movements every 5-6 days. Upon further questioning, he reported taking 6 to 7 TUMS antacid tablets (each containing 200mg calcium) daily for the past two months to treat ‘heartburn’. He denied having chest pain. His medications included hydrochlorothiazide, losartan, amlodipine, atorvastatin, glimepiride, and famotidine. On physical exam he had reduced strength in both lower extremities - 1/5 left, 3/5 right. EKG on arrival showed ST elevation in leads III, aVF, and V1-V5, with T wave inversions in aVR and aVL, suggestive of a STEMI. A STEMI code was called. Since he denied chest pain, troponins were lateralized at 0.1 ng/mL, and an echocardiogram showed no wall motion abnormalities, cardiology recommended conservative management. Laboratory evaluation revealed calcium of 15.5 mg/dL, albumin of 3.8 g/dL, BUN of 39 mg/dL, creatinine of 2.2 mg/dL, magnesium of 1.4 mg/dL, phosphorus of 3 mg/dL, 25-OH vitamin D of 24 ng/mL, PTH of 9 pg/mL, undetectable 1-25 OH vitamin D and PTHrP, and normal TSH and SPEP. CT head/chest/abdomen/pelvis showed no evidence of malignancy. He was treated with IV hydration and 1 dose of calcitonin. His calcium level, leg strength, and ST elevations began to improve within 12 hours and returned to normal within four days. Conclusion: Our patient had severe hypercalcemia likely secondary to excessive consumption of oral antacid tablets, as other causes were ruled out, and his EKG findings masqueraded as a STEMI-a rare presentation of hypercalcemia. Consumption of supplements may be overlooked when investigating hypercalcemia and should be specifically asked about. In addition, providers should be aware of EKG changes found in hypercalcemia to avoid unnecessary cardiac intervention.

Presentation: Saturday, June 17, 2023
SAT250 A Case Of Hypercalcemia In Pregnancy - A Diagnostic And Management Challenge
Authors: Cheng Wee Mee , Chien Kuan Yueh
Published: October 2023

Disclosure: W. Cheng: None. Y. Kuan: None.

Hypercalcemia in pregnancy is rare and poses significant diagnostic and management challenges especially in a low resource setting. Although primary hyperparathyroidism (PHPT) is the main cause, physiological changes in calcium homeostasis make it difficult to distinguish from familial hypocalciuric hypercalcemia (FHH) unless genetic testing is done. Furthermore uncertainty exists on the safety of pharmacotherapy for hypercalcemia in pregnancy which if untreated, can be detrimental to both mother and child. Described herein a 17 year-old primigravida who presented at 32 weeks of gestation for asthma exacerbation precipitated by COVID-19 infection. She was incidentally found to have PTH-dependent hypercalcemia with albumin-corrected calcium 3.42 mmol/L [2.10-2.55] associated with raised intact parathyroid hormone (iPTH) 15 pmol/L [1.6 - 6.0] and deficient serum 25OH Vitamin D at 19.95 nmol/L [50-125]. She was given IV saline of 3-3.5L/day but to no avail as her serum calcium was persistently above 3 mmol/L with an episode of premature uterine contraction. Calcitonin was given in short courses and withheld once albumin-corrected calcium dropped below 3 mmol/L but rebound within three days. As bisphosphonates is contraindicated in pregnancy, we introduced cinacalcet, up to 75mg/day after discussion with the patient and her family. Meanwhile, investigations were done to ascertain underlying cause. Fractional urine calcium excretion ranged from 0.0068 (spot urine sample) to 0.0568 (24-hour urine sample). Ultrasound neck did not reveal enlarged parathyroid glands or an adenoma. Sestamibi scan was contraindicated in pregnancy. Genetic testing for FHH was too costly but all her first-degree relatives tested to have normocalcemia. Blood pressure remained normal throughout pregnancy. She was discharged with cinacalcet at calcium level of 2.7 mmol/L. However she defaulted follow-up and medications and presented at 36 weeks of gestation for preterm labour. She gave birth to a healthy, 2.46kg baby girl. The baby had neonatal jaundice but normal calcium level. Postpartum, the patient was asymptomatic despite persistent hypercalcemia 3.12 - 3.15nmol/L. As she was non-compliant to cinacalcet it was stopped and serum calcium did not worsen. Sestamibi scan is planned after she stops breastfeeding and a reassessment of the urine calcium once vitamin D is adequately replenished. She refused exploratory parathyroidectomy. She continued to be followed up at the endocrine clinic while her baby at primary care. Contraception is advised untill definitive diagnosis and treatment of hypercalcemia. This case illustrates the challenges in managing hypercalcemia in pregnancy and difficulty in distinguishing PHPT vs FHH without genetic testing.

Presentation: Saturday, June 17, 2023
SAT256 Buschke Loewenstein Tumor Presenting With Hypercalcemia
Authors: Jones Kai , Krutilova Petra , McGill Janet B
Published: October 2023

Disclosure: K. Jones: None. P. Krutilova: None. J.B. McGill: None.

Introduction: Humoral hypercalcemia of malignancy is known to be associated with squamous cell carcinomas (SCC), although rarely seen in the setting of skin cancer. We present an interesting case of a young patient with giant condyloma acuminatum complicated by SCC presenting with severe hypercalcemia. Case Description: A 37-year-old man presented with pain and purulent drainage due to bacterial superinfection of genital warts. He had recurrent and locally advanced condylomas, first occurring more than 10 years ago. Skin lesions in the genital and perianal area never resolved and he required multiple surgical interventions including sigmoid colostomy placement due to Fournier gangrene. His laboratory evaluation this admission was notable for an elevated calcium level (13.0 mg/dL [8.5-10.3], albumin 3.4 g/dL [3.5-5.0]), phosphorus 3.9 mg/dL [2.3-4.5], and normal kidney function. He did not have history of hypercalcemia and was not taking any calcium supplements. Hypercalcemia prompted work-up including: PTH 4 pg/mL [15-65], 25-OH vitamin D 36 ng/mL [30-80], unremarkable SPEP/UPEP, TSH 0.91 mcIUnit/mL [0.3-4.2]. Initial differential diagnosis included hypercalcemia due to granulomatous process and increased production of calcitriol vs. PTH-related protein (PTHrP) mediated hypercalcemia. 1,25-OH vitamin D was normal (33 pg/mL [18-64]) and PTHrP was elevated (6.7 pmol/L [<4.2]). The patient subsequently underwent biopsy of groin lesions which demonstrated SCC in situ. PET/CT only demonstrated hypermetabolic changes in the perineum and groins bilaterally. Inguinal lymph node biopsy was negative for malignancy. His hypercalcemia persisted despite administration of IV fluids and he was treated with IV zolendronic acid. Calcium level subsequently normalized (9.1 mg/dL). He underwent extensive excision of the tumor involving the right gracilis muscle, left testicle, portions of the perineum, and penile shaft skin. Discussion: While cases of hypercalcemia in malignancy are common, this is an unusual case of giant condyloma acuminata (GCA) heralding development of SCC by elevated calcium levels. GCA also known as Buschke-Loewenstein tumor is a rare disease with estimated incidence of 0.1% in the general population and a male-to-female ratio of 2.7:1, typically associated with human papilloma virus subtypes 6 and 11. It is a locally aggressive tumor with a potential for destructive growth and malignant transformation (estimated rate up to 56%), very high rate of recurrence after excision (66%), and overall mortality of approximately 20%. Early recognition and treatment of GCA is essential in order to prevent devastating complications. Purzycka-Bohdan D, Nowicki RJ, Herms F, et al. The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview. Int J Mol Sci. 2022;23(9):4547. Published 2022 Apr 20. doi:10.3390/ijms23094547

Presentation: Saturday, June 17, 2023
OR23-06 Long Term Outcomes Of Parathyroid Autografts In Primary Hyperparathyroidism
Authors: Chuki Elias , Graf Akua , Ninan Anisha , Tora Rana , Abijo Tomilowo , Nilubol Naris , Scott Weinstein Lee , Kishore Agarwal Sunita , Simonds William F , Jha Smita
Published: October 2023

Disclosure: E. Chuki: None. A. Graf: None. A. Ninan: None. R. Tora: None. T. Abijo: None. N.M. Center: None. N. Nilubol: None. L.S. Weinstein: None. S.K. Agarwal: None. W.F. Simonds: None. S. Jha: None.

Background: Autologous implantation of parathyroid tissue is frequently utilized in patients with heritable forms of primary hyperparathyroidism (PHPT). There is sparse data on long-term functional outcome of these grafts and post-graft recurrence of PHPT. Objective: We aimed to investigate the long-term outcome of parathyroid autografts and assess the frequency of post-graft PHPT recurrence. Methods: Retrospective study of patients with PHPT who underwent parathyroid autografts from 1991 to 2020. Results: We identified 115 patients with PHPT who underwent 135 parathyroid autografts. A significant majority (106 of 115 patients, 92%) had a heritable form of PHPT, with MEN1 being the most common (93 of 115 patients, 81%). Median follow-up duration since graft was 10 [4-20] years. 119 (88%) were to brachioradialis, 11 (8%) to sternocleidomastoid and 5 (4%) to deltoid. There were 86 immediate (64%) and 49 delayed (36%) grafts. Of the 135 grafts, 54 (40%) were fully functional at last follow-up, 13 (10%) partially functional, 44 (32%) non-functional while functional status of 24 (18%) grafts could not be ascertained. Age at graft, thymectomy prior to autograft, graft type (delayed/immediate) or duration of cryopreservation did not predict functional outcome. There were 45 (83%) post-graft recurrences of PHPT among 54 fully functional grafts at a median duration of 8 [4-15] years after grafting. Parathyroidectomy was performed in 42/45 but surgical cure was attained in 18/42 (43%) only. 12 of 18 (67%) recurrences were graft-related while the remaining 6 (33%) had a neck or mediastinal source. Median time to recurrence was 16 [11-25] years in neck or mediastinal source versus 7 [2-13] years in graft-related recurrences. Median PTH gradient was significantly higher at 23 [20-27] in graft-related recurrence versus 1.3 [1.2-2.5] in neck or mediastinal source (P = 0.03). Nineteen patients had multiple parathyroid grafts. Median pre-repeat-graft PTH of 7.5 [6.5-18.5] pg/mL with ionized calcium of 1.15 ± 0.145 (reference:1.09-1.30) mmol/L served as an indicator of the need for a repeat graft. Discussion: Post-graft recurrence occurs frequently within the first decade after grafting. Source of excess PTH in post-graft recurrence of PHPT can be challenging to localize. Time to recurrence after graft is significantly shorter and PTH gradient higher for graft-related recurrence.

Presentation: Saturday, June 17, 2023
OR02-04 Peripheral Blood Steroid Profiling Discriminates Aldosterone-producing Adenoma Genotypes From Bilateral Primary Aldosteronism
Authors: Turcu Adina F , Lee Chaelin , Salman Zara , Liu Haiping , Rabbah Amira , Marie Konzen Sonja , Rainey William E , Giordano Thomas J , Zhao Lili , Udager Aaron
Published: October 2023

Disclosure: A.F. Turcu: None. C. Lee: None. Z. Salman: None. H. Liu: None. A. Rabbah: None. S.M. Konzen: None. W.E. Rainey: None. T.J. Giordano: None. L. Zhao: None. A. Udager: None.

Background: Primary aldosteronism (PA) is dichotomized into 2 major subtypes: unilaterally dominant PA, often caused by aldosterone-producing adenomas (APAs), and bilateral PA (BPA). Adrenal vein sampling (AVS)-guided unilateral adrenalectomy is often curative in patients with APA and offers marked cardiovascular and renal benefits. The diagnosis and subtyping of PA is a complex, multistep process, hindered by expertise and resource limitations. Objective: To develop steroid fingerprints that can distinguish genotype specific APAs from BPA in peripheral blood. Design And Methods: We enrolled 120 patients with PA who underwent AVS in a single tertiary referral center. Liquid-chromatography tandem mass spectrometry was used to simultaneously quantify 17 steroids in adrenal veins (AV) and periphery, both at baseline, and 10-20 min after cosyntropin stimulation. Aldosterone synthase (CYP11B2) immunohistochemistry-guided next generation sequencing was employed to identify aldosterone-driver mutations. Kruskal-Wallis tests were performed for comparison of continuous variables across multiple groups. Receiver operating characteristic (ROC) curves were plotted to discriminate APAs from BPA. Results: The 120 study participants included 75 patients with APA who underwent unilateral adrenalectomy and had documented aldosterone-driver mutations, and 45 patients with BPA. Of patients with APAs, 36 carried somatic mutations in CACNA1D, 24 in ATPase, and 15 in KCNJ5 genes, respectively. Patients with KCNJ5 mutations were younger and most were women. In the dominant AVs, the KCNJ5 group had marked elevations of 18-hydroxycortisol, 18-oxocortisol, aldosterone, and 11-deoxycorticosterone (DOC); conversely, the BB group had the lowest concentrations of mineralocorticoid and androgen precursors, despite comparable cortisol levels across all groups. Similar patterns were observed in peripheral blood. Linear discriminant analysis incorporating all steroids measured in baseline peripheral serum showed areas under the curve (AUC) of 0.98, 0.97, and 0.92 for distinguishing APAs with KCNJ5, ATPase, or CACNA1D mutations, respectively, from BPA. Conclusions: Single-assay steroid profiles measured in peripheral serum can distinguish genotype-specific APAs from BPA. Once validated, such tests might circumvent the need for AVS in large subset of PA patients.

Presentation: Thursday, June 15, 2023
THU585 Non-alcoholic Fatty Liver Disease (NAFLD), A Silent But Emerging Problem In Type 1 Diabetes
Authors: Taiwo Adeyinka , Merill Ronald , Wendt Linder , Pape Daniel , Thakker Himani , Pothireddy Nikitha , Carlson Bianca , Sanchez Antonio , Ten Eyck Patrick , Jalal Diana , Dokun Ayotunde , Taylor Eric , Sivitz William
Published: October 2023

Disclosure: A. Taiwo: None. R. Merill: None. L. Wendt: None. D. Pape: None. H. Thakker: None. N. Pothireddy: None. B. Carlson: None. A. Sanchez: None. P. Ten Eyck: None. D. Jalal: None. A. Dokun: None. E. Taylor: None. W. Sivitz: None.

Background: Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Risk factors include type 2 diabetes, insulin resistance and obesity. Although NAFLD has been widely studied in persons with type 2 diabetes, far less in known about the pathogenesis and severity of NAFLD in type 1 diabetes. Objective: The goal of this study was to understand the metabolic perturbations that contribute to the pathogenesis of NAFLD in type 1 diabetes. Study Design: We conducted a cross-sectional study of 30 participants with type1 diabetes recruited from our institutional diabetes clinic. To assess liver fat content and stiffness, a FibroScan was done. Based on the results, participants were stratified into a case group (evidence of NAFLD) or control group (no evidence of NAFLD). All participants had fasting plasma drawn to determine metabolites. Gas-Chromatography Mass Spectrometry was used for metabolomic analyses and Liquid Chromatography Mass Spectrometry for lipidomic and acylcarnitines analyses. Results: Sixteen of 30 participants were classified as cases and 14 as controls. Cases had higher BMI (P=0.001) and were taking higher daily insulin doses than controls (P=0.008). Metabolomic analyses revealed that cases had elevated levels of glutamate (P=0.001), alanine (P=<0.001), pyruvate (P=<0.001), phenylalanine (P = 0.005), lactate (P=0.019) and anthranilic acid (P=0.029). Lipidomics revealed that, cases had elevated ceramides (P= 0.02), diacylglycerol (P=0.0003) and triacylglycerol (P=0.0003). The acylcarnitine, isovalerylcarnitine (CAR.5.0) a metabolite of isoleucine catabolism, was elevated in the cases (P = 0.010). Pathway enrichment analysis revealed, phenylalanine and tyrosine metabolism, tryptophan metabolism, glucose-alanine cycle, glutamate metabolism and glutathione metabolism were significantly enriched in the cases. Conclusion: We observed evidence of elevated metabolite levels involved in gluconeogenesis, glucose-alanine metabolism, energy metabolism, insulin resistance, and dysfunctional fat synthesis in the cases compared to controls. Our cases had some features similar to Type 2 diabetes with NAFLD, with evidence of elevated levels of aromatic amino acids, ceramides, diacylglycerol and triacylglycerol. However unlike Type 2 diabetes, there was no elevation of branched-chain amino acids levels.

Presentation: Thursday, June 15, 2023
THU595 New Screening Cutoff Values For Detection Of Aldosterone Producing Adenoma Examined By LC-MS/MS And Newly Developed Non-competitive Cleia
Authors: Satoh Fumitoshi , Ono Yoshikiyo , Omata Kei , Tezuka Yuta , Yamazaki Yuto , Sasano Hironobu , Kojima Satoshi
Published: October 2023

Disclosure: F. Satoh: None. Y. Ono: None. K. Omata: None. Y. Tezuka: None. Y. Yamazaki: None. H. Sasano: None. S. Kojima: None.

Objective: Thinking of the poor accuracy of conventional CLEIA measurements of aldosterone, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method but it is costly, labor intensive and time consuming. A novel non-competitive chemiluminescent enzyme immunoassay (sandwich assay) (NC-CLEIA) for measuring aldosterone was recently developed. We validated the accuracy and diagnostic ability of the NC-CLEIA and compared the results obtained with those by LC-MS/MS and also determined the new screen cutoffs by both measurements, respectively, detecting aldosterone-producing adenoma (APA) in hypertensive patients. Design and Method: We measured plasma renin activity by enzyme assay and plasma aldosterone concentrations (PAC) using LC-MS/MS and NC-CLEIA in 133 APA, 100 bilateral hyperaldosteronism and 111 essential hypertension patients to examine the accuracy of the values of PAC measured by this new NC--CLEIA as compared with those by LC-MS/MS, and determine the new screen cutoff values by both measurements to detect APA, respectively. Results: Passing-Bablok analysis revealed that NC-CLEIA (regression slope, intercept and correlation coefficient were 0.962, -0.043, and 0.994, respectively), was significantly correlated and equivalent to LC-MS/MS than RIA. Bland-Altman plot analysis of NC-CLEIA by LC-MS/MS also demonstrated much smaller systemic errors (a bias of -0.348 ng/dL with limits of agreement of -4.390 and 3.694 and 95% confidence interval). The receiver-operating characteristics analysis demonstrated that cut-off values of aldosterone/renin activity ratio obtained by LC-MS/MS and NC-CLEIA were 31.2 and 31.5 (ng/dL per ng/mL/hr) with a sensitivity of 91.0% and 90.2%, and a specificity of 75.4% and 76.8%, respectively, in terms of discriminating APA from non-APA. Therefore, we can recommend an ARR > 30.0 ng/dL per ng/mL/hr as a screening cut-off by both LC-MS/MS and NC-CLEIA, which would discriminate APA with a sensitivity of 91.7% in both assays, and with a specificity of 73.0% and 73.9 %, respectively. Conclusions: This novel NC-CLEIA assay for PAC could serve as a clinically reliable alternative to LC-MS/MS to detect APA among hypertensive patients with more accuracy than the conventional methods.

Presentation: Thursday, June 15, 2023
FRI128 Hiding In Plain Sight: Late Diagnosis Of Primary Hyperaldosteronism In Patient With Atypical Presentation
Authors: Zielinski Rachel A , Syeda Asma , Esayag-Tendler Beatriz
Published: October 2023

Disclosure: R.A. Zielinski: None. A. Syeda: None. B. Esayag-Tendler: None.

Background: Primary hyperaldosteronism (PHA) can go undiagnosed in patients with primary hypertension without hypokalemia and increased plasma aldosterone concentration (PAC). Case: The patient is a 72-year-old male with a history of hypertension (HTN) diagnosed at age 55 who presented to the endocrinology clinic for further evaluation. He was asymptomatic. His antihypertensive regimen included atenolol 25 mg daily and amlodipine-benazepril 10-40 mg daily. Blood pressure (BP) was well-controlled with a goal BP under 130/80 mm Hg. Physical exam was without AV nicking in a limited retina exam, no abdominal tenderness, and no peripheral edema. Family history is notable for HTN in his father and HTN complicated by stroke in a sister and a brother, all diagnosed at an older age. Labs done 5 years prior showed potassium (K) of 4.3 mmol/L [3.6 - 5.1 mmol/L], PAC of 3.2 ng/dl [upright 4.0 - 31.0 ng/dl], and plasma renin activity (PRA) of 0.1 ng/ml/hr [upright 0.5-4.0 ng/ml/hr]. More recent labs showed K of 3.8 mmol/L, PAC of 21.5 ng/dl and PRA of 0.3 ng/ml/hr. Repeat labs 6 months later showed K of 3.4 mmol/L, PAC of 15 ng/dL and PRA of 0.2 ng/mL/hr. A 3-day dexamethasone suppression test was performed to exclude familial hyperaldosteronism or glucocorticoid remediable aldosteronism. Following the test, K was 3.6 mmol/L, PAC was 11.3 ng/dl, and cortisol was undetectable. CT abdomen showed bilateral nodular thickening of the adrenal glands without a distinct adenoma. Adrenal venous sampling was done before and after ACTH stimulation. Prior to ACTH stimulation, the mean ratio of the dominant adrenal aldosterone concentration corrected with cortisol from left to right was 1.32. Following ACTH stimulation, the ratio was 2.79. A ratio greater than 4 is consistent with a good outcome after adrenalectomy. Hence, it was decided to pursue medical management. The cause of our patient’s primary hyperaldosteronism is likely due to bilateral idiopathic hyperplasia. He was started on eplerenone 25 mg twice daily and salt restriction with a goal of increasing the PRA above 1 ng/ml/hr. Discussion and Conclusion: It was initially thought that PHA represents 1% of all patients with primary HTN. However, more recent studies indicate that the prevalence is significantly higher. Additionally, the PAC in patients with PHA can fluctuate and patients can present with normokalemia, making the diagnosis more difficult to establish. It is an important diagnosis to establish and treat appropriately because there is a higher risk of cardiovascular morbidity and mortality in patients with PHA compared to patients with primary HTN.

Presentation: Friday, June 16, 2023
FRI132 Aldosterone Secretory Capacity Immediately After Surgery Predicts Biochemical Outcome 1 Year After Surgery In Primary Aldosteronism
Authors: Ishida Yuto , Nakai Kazuki , Tsurutani Yuya , Watanabe Kazuki , Saito Jun , Nishikawa Tetsuo
Published: October 2023

Disclosure: Y. Ishida: None. K. Nakai: None. Y. Tsurutani: None. K. Watanabe: None. J. Saito: None. T. Nishikawa: None.

Background and Objective: In primary aldosteronism (PA), the biochemical outcome of the Primary Aldosteronism Surgical Outcome (PASO) study is used to assess aldosterone hypersecretion six months to one year after surgery. However, there are few reports on whether outcomes can be predicted in the early postoperative period. This retrospective study evaluated aldosterone secretory capacity immediately after surgery using the adrenocorticotropin (ACTH) stimulation test (AST) and oral salt loading test (OST). We hypothesized that these tests would predict biochemical outcomes one year after surgery. Methods: This study assessed 282 patients with PA who underwent adrenalectomy in our hospital between 2008 and 2020 and determined biochemical PASO outcomes 1 year after surgery. Patients with serum cortisol levels ≥ 5 μg/dL after a 1 mg overnight dexamethasone suppression test (n = 9) were excluded. Patients were divided into biochemical complete success (COM) and incomplete (partial + absent) success (INC) groups. AST and OST were performed within 15 days of surgery. The relationships between various AST and OST values and outcomes were analyzed. Results: Two hundred and twenty patients and 53 patients were classified into the COM and INC groups, respectively. The INC group had significantly higher plasma aldosterone concentration (PAC) and higher PAC/cortisol ratio (A/C) at baseline, 30 min, and 60 min after ACTH loading than the COM group. The INC group showed a significantly lower level of plasma renin activity. In the OST, the INC group had a significantly higher 24-hour urine aldosterone level. Of these values, A/C at 30 minutes after ACTH loading (area under the curve (AUC) = 0.77) and 24-hour urine aldosterone (AUC = 0.78) were relatively superior predictors of the outcome, with higher AUCs than plasma renin activity (AUC = 0.63), baseline PAC (AUC = 0.71), baseline ARR (AUC = 0.72), and baseline A/C (AUC = 0.70). A/C at 30 minutes after ACTH loading had 83% sensitivity and 62% specificity when 6.03 was set as the cutoff; 24-hour urine aldosterone had 84% sensitivity and 61% specificity when 2.6 was set as the cutoff. Conclusion: AST and OST immediately after surgery are useful for predicting biochemical outcomes 1 year after surgery in patients with PA.

Presentation: Friday, June 16, 2023
FRI133 Diagnosis Of Liquorice Induced Hypertension By Mass Spectrometry - A Simpler And Less Expensive Method
Authors: Daníel Árnason Árni , Sigurdsson Baldur Bragi , Cook Elizabeth , Þorsteinsdóttir Margrét , Wallerstedt Sven , Agusta Sigurjonsdottir Helga
Published: October 2023

Disclosure: Á.D. Árnason: None. B.B. Sigurdsson: None. E. Cook: None. M. Þorsteinsdóttir: None. S. Wallerstedt: None. H.A. Sigurjonsdottir: None.

Background: The diagnosis of liquorice induced hypertension (LIH) has been confirmed by measuring the urinary ratio of free cortisol/cortisone by gas chromatography. The aim of this study was to evaluate if analysis of this ratio in serum (QS) is as sensitive and selective compared to analysis of the urinary ratio (QU) using mass spectrometry (LC-MS/MS) and if the analysis of serum GA (glycyrrhetinic acid) correlates to the ratio of QS in order to diagnose LIH. Methods: We included 125 individuals, 117 normotensive (NT) and 8 hypertensive (HT). Mean age was 31.6 years for the whole group (W), 31.1 years for NT, 39 years for HT, 31.1 years for men (n=72) and 32.2 years for women (n=53). The study was prospective and double blind, participants consuming 150 mg of capsuled GA daily for 2 weeks (n= 62) or placebo (n=63). Highly selective and sensitive validated inhouse LC-MS/MS method, able to measure both serum and urine samples, was used to quantify free cortisol and cortisone. An additional validated in-house method was used to quantify serum 18β-GA. Mean values with standard deviation of QS, QU and serum GA was obtained for W and the subgroups. The mean difference (mdiff) in QS, QU and serum GA before and after GA intake (or placebo) was evaluated with Wilcoxon test and correlation by Spearman correlation test. Results: For W the mdiff for QS was 0.936 (±3.19, p<0.001) and for QU it was 0.214 (±0.493, p<0.001), QS and QU correlated (p<0.001, rho=0,605). For NT the mdiff for QS was 0.877 (±3.22, p<0.001) and for QU it was 0.203 (±0.498, p<0.001), Qs and QU correlated (p<0.001 and rho=0.610). For HT the mdiff for QS and QU was not significant. For men the mdiff for QS was 1.30 (±2.85, p<0.001) and for QU it was 0.241 (±0.474, p<0.001), QS and QU correlated (p<0.001, rho=0.635). For women the mdiff of QS was 0.446 (±3.58, p=0.00816) and for QU it was 0.176 (±0.520, p=0.0360), Qs and QU correlated (p<0.001, rho=0.477).The mdiff for GA for W was 6.78x105 (±1.04x106, p<0.001), for the NT the mdiff in GA was 6.50x105 (±1.00x106, p<0.001), for HT it was not significant. For men it was 7.18x105 (±9.15x105, p<0.001) and for women it was 6.24x105(±1.19x106, p=0.0140). There was a positive linear relationship between the mdiff of QS and GA and QU and GA, for all groups (p<0,05). Conclusions: We conclude that the new inhouse LC-MS/MS method is a sensitive and reliable method to evaluate Qs, Qu and serum GA. Further, this new inhouse method is a reliable method to diagnose LIH.

Presentation: Friday, June 16, 2023
FRI148 Adrenal Vein Sampling: Intra-protocol Hormonal Variability
Authors: Lee Chaelin , Salman Zara , Shields James , Turcu Adina F
Published: October 2023

Disclosure: C. Lee: None. Z. Salman: None. J. Shields: None. A.F. Turcu: None.

Background: Primary aldosteronism (PA) might arise from one or both adrenal glands. Treatment of PA relies on determining the relative contribution of aldosterone from the two adrenal glands. Adrenal vein sampling (AVS) is essential to identifying patients with lateralized PA (LPA), who benefit from surgery. AVS procedure and interpretation protocols differ between centers. Variability in AVS lateralization has been primarily attributed to cosyntropin use and lateralization index (LI) thresholds. However, data on intra-protocol variability are lacking. Methods: We retrospectively reviewed the clinical records of patients with PA who underwent AVS at University of Michigan between January 2015 and December 2022. In our center, AVS is performed both before and after cosyntropin stimulation, and 6 sets of paired adrenal vein and peripheral serum are obtained: 3 at baseline, and 3 between 5-30 min after cosyntropin stimulation. We included patients who had successful adrenal vein catheterization and valid data from 6 time points. A LI≥4 was considered indicative of LPA. We assessed the rates of inconsistent AVS results within baseline and cosyntropin stimulated samples as proportion of sets in which 1/3 LIs provided different subtyping results than the other 2/3. Results: Of 361 patients included, 107 (29.6%) patients had at least one inconsistent LI. Of these, 74 (20%) patients had an inconsistent LI within the basal sets, 45 (12%) within the cosyntropin stimulated sets, and 12 (3.3%) patients had a discrepant result in both baseline and cosyntropin stimulated sets. The highest outlier rates were observed in the first basal sample (30.3%), followed by the third basal sample (21.9%), the first post-cosyntropin sample (16.0%), and the last post-cosyntropin sample (13.5%). Patients with one intra-protocol outlier were younger (mean age 52.2 ± 11.5 vs. 56.2 ± 10.8 years), but there were no sex, race distribution, or BMI differences between the two groups. Conclusions: The intra-procedural AVS data variability is almost twice as high in basal vs. post-cosyntropin stimulation sampling, particularly in the initial set, likely mediated by acute ACTH fluctuations during the procedure. Our results emphasize the importance of obtaining multiple AVS data sets, in order to best inform the decision for or against surgery.

Presentation: Friday, June 16, 2023
FRI149 Internal Medicine Residents Knowledge On Testing For Treatment Resistant Hypertension With The Focus On Primary Aldosteronism - Interim Analysis
Authors: Markovic Nikolina , Brankovic Milos , Palani Arthi , Matassa Daniel
Published: October 2023

Disclosure: N. Markovic: None. M. Brankovic: None. A. Palani: None. D. Matassa: None.

Studies have shown that primary aldosteronism (PA) is an underlying cause in up to 23% of patients diagnosed with treatment-resistant hypertension (TRH).1 However, recent data have suggested that less than 2% of TRH patients would undergo testing for PA despite strong guideline recommendations.2 Given that PA is an easily diagnosed and treatable cause of TRH, our goal was to identify modifiable factors that can increase diagnosis of secondary causes of TRH. Therefore, we aimed to investigate the residents’ knowledge on diagnosis and evaluation of TRH with the focus on PA. This anonymous survey included Internal Medicine residents during their Ambulatory Clinic Rotation. The response rate was 66% with equal distribution across PGY 1-3. Total of 75% of residents defined TRH correctly, but only 66% of all residents would pursue additional testing to identify the secondary causes of TRH in patients who meet criteria for TRH. On average, only 45% of all residents reported having at least one patient with TRH in the past six months. Upon stratification, this percentage increased among PGY-3 residents (61%). Most residents (96%) knew that the renin-to-aldosterone ratio is an appropriate screening method for PA. Appropriately when listed possible options for evaluation of secondary causes of TRH 93% of residents would order plasma renin activity, and 87% would order plasma aldosterone concentration. Among other tests that residents would perform are: TSH (87%), renal ultrasound with arterial Doppler (75%), CBC (34%), and almost one third of residents (27%) would order transthoracic echocardiogram. Furthermore, 43% of residents would discontinue both ACE/ARB and spironolactone, whereas 25% would discontinue only spironolactone for 6 weeks before testing. Sixty percent of residents were interested in learning more about TRH.The most striking finding of this study is that despite most of the residents appropriately identified tests for secondary causes of TRH, only two thirds of residents would investigate secondary causes of TRH in their practice. This may be the contributing factor for underdiagnosis of PA. Additional guidance on therapy that does not interfere with screening tests for PA is needed. In phase 2 of this study, we plan to provide more education in this area to improve the blood pressure control and decrease the risk of cardiovascular morbidity and mortality in TRH patients. References:1. Huang WC, Lin YH, Wu VC et al. Who should be screened for primary aldosteronism? A comprehensive review of current evidence. J Clin Hypertens (Greenwich). 2022;24(9):1194-1203.2. Cohen JB, Cohen DL, Herman DS et al. Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans: A Retrospective Cohort Study. Ann Intern Med. 2021;174(3):289-297.

Presentation: Friday, June 16, 2023
SAT076 Olanzapine Induced Pancreatitis
Authors: Mandhan Akash , Friedman Naomi , Stefan Simona
Published: October 2023

Disclosure: A. Mandhan: None. N. Friedman: None. S. Stefan: None.

Background: Olanzapine, an atypical antipsychotic, is commonly used to treat a variety of mental health conditions, including schizophrenia, bipolar disorder, and depression. Acute pancreatitis from olanzapine is rare. Drug-induced pancreatitis represents 0.1-2% of all cases of acute pancreatitis. Here we describe a case of olanzapine induced severe pancreatitis and new onset of diabetes. Clinical Case: A 43-year-old male with history of bipolar disorder was admitted with vomiting and altered mental status. Symptoms began a week prior to presentation and included polydipsia and polyuria. He had no known history of hyperlipidemia, diabetes or alcohol use. He was treated with olanzapine for six months prior to presentation, and the dose was increased to 35mg/day one month prior to hospital admission. On exam, he appeared older than his stated age, confused, restless and dehydrated. He was afebrile but tachycardic and hypotensive. Laboratory evaluation was notable for glucose of 1619 mg/dL (70-140 mg/dL) metabolic acidosis with ketonuria, lipase level of 684 U/L (n<60), and triglyceride (TG) level of 1574 mg/dL (<150 mg/dL). CT of the abdomen showed severe acute interstitial pancreatitis with retroperitoneal fluid and possible necrosis, normal-appearing gallbladder, no cholelithiasis. He was made NPO, and started on IV fluids and IV Insulin therapy. His HbA1C was 12.6% with negative GAD and IA2 antibodies, consistent with type 2 diabetes. Within twenty-four hours of presentation his DKA resolved, and TG levels down trended below 1,000 mg/dL. He was transitioned to subcutaneous insulin and combination therapy of fenofibrate. The patient was discharged on basal insulin, metformin, fenofibrate, a low dose statin and omega-3 fatty acids. His TG at discharge was 210 mg/dL and olanzapine was not restarted. Conclusions: Olanzapine induced pancreatitis has been described as a rare cause of pancreatitis in the literature. To date, there is only one additional case report about acute necrotizing pancreatitis from olanzapine. Given the ubiquitous use of olanzapine in treating psychiatric disorders, it is important that physicians are aware of this rare but potentially life-threatening adverse reaction. The exact mechanism by which olanzapine causes pancreatitis is unclear, and case reports suggest hypertriglyceridemia as the most common proposed etiology of olanzapine-induced acute pancreatitis. Patients should have a screening lipid panel before beginning therapy to optimize treatment outcomes.

Presentation: Saturday, June 17, 2023
OR24-03 Triglyceride Clearance In Hypertriglyceridemic Pancreatitis: Time-course And Implications For Management
Authors: Majumdar Sachin K
Published: October 2023

Disclosure: S.K. Majumdar: None.

Introduction: Uncertainty exists for how to optimally manage severely elevated triglyceride (Tg) levels in patients with hypertriglyceridemic (HTg) pancreatitis. Standard recommendations include NPO (nil per os) status and intravenous (iv) insulin for most patients, yet information is lacking in regards to the natural time-course of Tg lowering, the degree of benefit insulin provides and for whom it may be indicated, and for the Tg level at which transition to feeding would be appropriate. Underlying Questions: (1) What is the natural time-course of triglyceride (Tg) lowering when nutritional intake is held and (2) does it differ according to etiology of hypertriglyceridemia? (3) What is the role of intravenous insulin in acute Tg lowering, and (4) at what threshold of Tg can nutritional intake safely resume? Methods: A retrospective study of patients hospitalized from October 2013 through December of 2018 with a diagnosis of pancreatitis associated with hypertriglyceridemia Tg ≥ 5.65 mM (500 mg/dL), in absence of other causes, was performed by medical record review. The time-course of Tg lowering was assessed for differences in relation to initial Tg values, use of iv insulin, ethanol vs. non ethanol associated causes, and time to Tg values of < 5.65 mM (500 mg/dL) vs < 11.29 (1000 mg/dL). Results: Sixty-six cases were identified and 45 had multiple measurements for time-course evaluation. Those with initial Tg values < 45.16 mM (4000 mg/dL) achieved Tg levels < 11.29 mM in < 3 days, while 18.8% with higher values took 5-9 days. Insulin therapy was associated with a longer duration, and ethanol with a shorter duration, of hypertriglyceridemia. Tg clearance in ethanol associated hypertriglyceridemia appeared independent of insulin treatment. Time to Tg < 5.65 mM vs < 11.29 mM was significantly longer when initial Tg levels were > 22.58 mM (2000 mg/dL). Conclusion: An arbitrary threshold of 45.16 mM (4000 mg/dL) for initial Tg’s in HTg pancreatitis appears to separate those likely to achieve Tg’s < 11.29 mM in < 3 vs. > 3 days, independent of cause or treatment in absence of known genetic defects in Tg clearance. Insulin therapy remains appropriate for hyperglycemic patients but appears unnecessary for isolated ethanol associated hypertriglyceridemia. A threshold Tg of <11.29 mM appears more practical than <5.65 mM for resuming nutritional intake. A randomized trial is necessary to confirm these findings.

Presentation: Saturday, June 17, 2023
THU105 PHH Parameters Are New Minimal-Invasive Markers Of Glycemic Homeostasis Of Type 1 Diabetes
Authors: Harvengt Antoine
Published: October 2023

Disclosure: A. Harvengt: None.

Aims: Recently, our team introduced the concept of post-hypoglycemic hyperglycemia(PHH) in the context that recovery of hypoglycemia impacts cardiovascular risk.GLUREDIA study aimed to evaluate whether PHH parameters correlated with glycemichomeostasis during the first year after type 1 diabetes onset and helped to distinguishpediatric patients undergoing partial remission or not. Methods: In the GLUREDIA study, longitudinal values of clinical parameters,continuous glucose monitoring metrics and residual beta-cell secretion from childrenwith new-onset type 1 diabetes were analyzed for one year. PHH is defined as anyhypoglycemia followed within two hours by hyperglycemia. PHH parameters werecalculated using an in-house built algorithm. Cross-sectional correlations betweenPHH parameters (i.e., PHH frequency, PHH duration, PHHAUC) and glycemichomeostasis markers were performed using adjusted mixed-effects models. Results: PHH parameters were strong markers to differentiate remitters from non-remitters (all p < 0.001), the most sensitive being PHH/Hyperglycemia duration ratio(cut-off < 0.02, sensibility: 86%, specificity: 68%). Among those, PHHAUC correlatedwith clinical parameters and continuous glucose monitoring metrics and inverselycorrelated with residual beta-cell secretion (all R2 > 0.22, p < 0.001). Furthermore,combination of PHH parameters identified three groups of patients that might benefitfrom distinct therapeutic management. Finally, patient classification into fourglucotypes, as previously described, independently validated PHH parameters asreliable markers of glycemic homeostasis and improved the segregation of patientswith intermediate values of IDAA1C and CPEPEST. Conclusion: PHH parameters are new minimal-invasive and easily assessed markersof partial remission and glycemic homeostasis during the first year of type 1 diabetesthat allow patient-specific therapeutic management.

Presentation:
THU259 Alpelisib-induced Diabetic Ketoacidosis: Call For A Multidisciplinary Approach
Authors: Kalara Niketa , Rios Paola , Vendrame Francesco
Published: October 2023

Disclosure: N. Kalara: None. P. Rios: None. F. Vendrame: None.

Introduction: Alpelisib is a p110a subunit phosphatidylinositol-3kinase inhibitor (PI3K) approved for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA mutated, advanced or metastatic breast cancer. PI3K signaling is essential for the metabolic action of insulin and the inhibition of p110a subunit is associated with hyperinsulinemia and hyperglycemia. In the combination (Alpelisib-Fulvestrant) arm of phase III SOLAR-1 study the all-grade incidence of hyperglycemia was 63%, but diabetic ketoacidosis (DKA) was also observed and reported in 0.7% of patients. To the best of our knowledge, less than 10 cases of Alpelisib-induced DKA have been reported in the literature. Here we describe an additional case. Case Description: A 62-year-old female with a history of metastatic breast cancer, hypertension, and prediabetes, presented with 3 days of nausea, vomiting, abdominal pain, weakness, polyuria, and polydipsia. Fifteen days prior to the presentation the HbA1c was 6.1% for which she was started on metformin 500 mg daily. Alpelisib 150 mg PO BID and Fluvestrant (Estrogen receptor antagonist) were also started the same day. The patient was told to stop the PIK3 inhibitor if the blood glucose increased above 200 mg/dL. The review of system was positive for fatigue, decreased appetite, malaise, 5 lbs weight loss during the previous week, and headache. She had no family history of any endocrinologic disease. The physical exam was unremarkable with no signs of insulin resistance. Laboratory tests revealed pH 7.31 (7.35-7.45), HCO3 10 mmol/L (22-26), PCO2 21 mmHg (35-45), glucose 884 mg/dL (74-106), sodium 120 mmol/L (136-145), K 5.2 mmol/L (3.5-5.1), Cl 93 mmol/L (98-107), CO2 7 mmol/L (21-32), anion gap 22 mmol/L (5-15), GFR 30 mL/min/1.73m2 (>60), Cr 1.80 mg/dL (0.5-1.02), BUN 43 mg/dL (7-18), beta-hydroxybutyrate 3 mmol/L (0.4-0.5), HbA1c 9.2% (4.2-5.6). Additional testing revealed C-peptide 2.3 ng/ml (1.1-4.4) with glucose 397 mg/dL. Results suggested a combined DKA and hyperosmolar hyperglycemic state (HHS). Alpelisib was discontinued and the patient was managed with insulin drip, fluids, electrolyte replacement, and eventually transitioned to a basal-bolus regimen (0.5U/kg). The patient was discharged on metformin and Insulin glargine with the recommendation to follow up with endocrinology and oncology. Conclusion: Our case highlights the importance of blood glucose and HbA1c screening before starting Alpelisib with emphasis on a multidisciplinary approach to monitor blood glucose levels to prevent DKA.

Reference: 1. Farah SJ, Masri N, Ghanem H, Azar M. Diabetic ketoacidosis associated with alpelisib treatment of metastatic breast cancer. AACE Clin Case Rep. 2020;6(6):e349-e351. doi: 10.4158/ACCR-2020-0452

Presentation: Thursday, June 15, 2023
THU264 Enteric Activity Enhanced Ileal GLP-1 Secretion
Authors: Chen Yixin , Jiao Gege , Lei Yaru , Li Yufan , Sha Lei
Published: October 2023

Disclosure: Y. Chen: None. G. Jiao: None. Y. Lei: None. Y. Li: None. L. Sha: None.

GLP-1 is a multifunctional endocrine hormone secreted by intestinal L cells in gastrointestinal tract contributing to the maintenance of glucose homeostasis. The distal part of small intestine such as ileum has a great density of L cells. In this study, we provided a direct evidence that enteric activity modulated GLP-1 secretion in rat ileum. Methods: A segment of rat ileum was dissected. The proximal section of the ileum segment was used to pace the enteric activity with an intestinal electrical stimulation(IES) designed from our previous intestinal myoelectric activity analyzing mimicking the ileum activity in feeding and the adjacent distal section was perfused vascularly to collect and measure GLP-1 secretion. Ileal motility in the distal section of the ileum segment was also recorded to monitor the enteric activity. The lumen of the ileum segment was filled with saline. Results: The frequency and the amplitude of spontaneous contraction in the distal ileum section was 14.14±2.82 cycles/min and 1.58±0.46 g (n=5). The area under curve (AUC) was 180.40±61.68 g·s. The GLP-1 secretion level in the distal ileum section was 15.47±0.46 pg/mL. With IES, The frequency was increased to 18.27±2.23 cycles/min (P<0.05, n = 5) and the AUC was increased to 303.64±79.75 (p<0.05). The amplitude had no significant change (P>0.05). The GLP-1 secretion was significantly increased to 24.71±2.47 pg/mL(p<0.05) with enhanced enteric activity. we provided a direct evidence to show the enhancement of GLP-1 secretion with enteric activity. Our result indicated that with feeding-simulated enteric activity, GLP-1 secretion could be elevated by around 60 percent in rat ileum. (supported by the National Natural Science Foundation of China, Grant No.81670492)

Presentation: Thursday, June 15, 2023