bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT186 Young Patient With Primary Hyperparathyroidism And Mutation Of CDKN1B Gene MEN 4 Variant
Authors: Faria Briceno Judith Jackelyn , Jande Suraj S , Lairmore Terry , Rajini Kanth Reddy Yatavelli
Published: October 2023

Disclosure: J.J. Faria Briceno: None. S.S. Jande: None. T. Lairmore: None. R.R. Yatavelli: None.

Background: Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT)accounting for 80-85% of the cases. PHPT most commonly manifests between 50-60 years of age and when it presents at younger age, it can be associated with inherited genetic conditions like multiple endocrine neoplasia or Hyperparathyroid Jaw tumor syndrome. Clinical Case: A 34-year-old male without significant past medical history was noted to have elevated serum calcium on routine lab work and was advised to promptly go to the emergency room for further evaluation. In the ED, the patient’s corrected calcium was 13.8 mg/dL (normal range 8.7 - 10.5 mg/dL), ionized calcium elevated at 1.77 mmol/L (normal range 0.90 - 1.20 mmol/L), PTH was 786.2 pg/mL (normal range 9 - 77 pg/mL). The patient denied any history of fractures, kidney stones or bone pain. Patient was treated medically with IV fluids and calcium lowering agents. Given the elevated PTH, ultrasonography of the neck was done which revealed an oval, hypoechoic lesion measuring 1.2 x 2.25 cm with increased vascular flow posterior to the right thyroid lobe consistent with parathyroid adenoma. Parathyroidectomy was performed with excision of right inferior parathyroid adenoma measuring 2.7 x 1.2 x 0.6 cm (1.25 grams). The preoperative PTH level was 997.7 pg/mL, which rapidly improved 20 minutes post tumor excision to 75.9 pg/mL, a 90% fall in PTH level suggestive of successful tumor excision. The patient’s post-operative period was uneventful. Considering the very young age of presentation; hyperparathyroidism genetic panel was obtained to rule out any inherited conditions like MEN1 or Hyperparathyroid Jaw tumor syndrome. Genetic testing revealed a germline missense mutation in CKDN1B (variant c.287C >, heterozygous) and classified as Variant of Uncertain significance). Mutations in the cyclic dependence kinase inhibitor 1B (CDKN1B) have been identified as the culprit for tumor growth seen in multiple endocrine neoplasia 4. MEN4 is a rare autosomal dominant endocrine tumor syndrome characterized by hyperparathyroidism and pituitary adenomas. The variant described in our patient has classically not been associated with other tumors and the available evidence is currently insufficient to determine the role of this variant in disease and hence classified as Variant of Uncertain Significance. Conclusion: Genetic testing should be considered in patients with primary hyperparathyroidism who present at very young age or have multiglandular disease. Our patient does not have any other classic features of MEN 4 and as the genetic mutation is classified as Variant of Uncertain Significance, patient would be monitored clinically, and caution exercised before using this result to inform clinical management decisions.

Presentation: Saturday, June 17, 2023
SAT189 Giant Parathyroid Adenoma
Authors: Shah Siddharth , Fujikawa Priscilla
Published: October 2023

Disclosure: S. Shah: None. P. Fujikawa: None.

Parathyroid adenomas rarely weigh more than 4 grams. Our patient had a 5.3gram adenoma causing bilateral knee pain limiting mobility, constipation, low back pain, and frontal headache. Presenting with calcium of greater than 17 mg/dL, patient was treated with 2 rounds of hemodialysis, calcitonin, Zoledronate, and aggressive IV hydration to decrease calcium levels prior to parathyroidectomy. Patient then went onto develop Hungry bone syndrome which was treated with calcium carbonate and calcitriol. This rare giant parathyroid adenoma presents a unique opportunity to learn about pathogenesis and treatment of longstanding hyperparathyroidism causing hypercalcemia associated symptoms and hungry bone syndrome after parathyroidectomy.

Presentation: Saturday, June 17, 2023
SAT228 Denosumab Associated Severe Hypocalcemia Due To Vitamin D Deficiency In A Patient With Undiagnosed Primary Hyperparathyroidism
Authors: Reddy Bendaram Snigdha , Bhatt Plukshi J , Kantorovich Vitaly
Published: October 2023

Disclosure: S. Bendaram: None. P.J. Bhatt: None. V. Kantorovich: None.

Background: The Human monoclonal antibody, Denosumab is a widely used antiresorptive therapy for Osteoporosis, which in the presence of risk factors can lead to hypocalcemia. We present an interesting case of severe and prolonged hypocalcemia due to Denosumab therapy, due to Vitamin D deficiency from malabsorption, despite the presence of undiagnosed Primary Hyperparathyroidism (PHPT). Case Presentation: 74-year old white female with a history of Crohn’s disease s/p ileostomy, Osteoporosis on Denosumab, Seizure disorder on Divalproex, and Parkinson’s disease presented to the ED for worsening altered mental status and decreased oral intake for at least 2 weeks prior to admission. On presentation, she was alert, oriented to person only, complaining of body aches. She was on no vitamin D supplements. Vital signs were unremarkable except for low BMI of 17.05 kg/m2. Physical exam revealed a chronic upper extremity tremor and a new facial mouth tremor associated with bruxism. Chvostek and Trousseau signs were negative, however this was after 1 dose of IV calcium gluconate in the ED. On presentation, initial labs revealed total calcium of 5.3 mg/dL [8.7-10.5], Albumin 4.7 g/dL [3.4-4.8], Magnesium 1.2 mg/dL [1.6-2.7], creatinine 1.5 mg/dL [04-1.1] (baseline 1.0). Further testing showed ionized calcium of 0.56 mmol/L [1.17-1.33], 25 Hydroxy Vitamin D 9 ng/mL [30-100], PTH 777 pg/mL [15-65] and phosphorus 3.6 mg/dL [2.7-4.5]. She was treated with IV calcium gluconate, 50,000 IU weekly vitamin D3 and calcium citrate 950mg oral BID, followed by which her total calcium went up to 12 mg/dl, with ionized calcium elevated at 1.36 mmol/L, while herPTH levels stayed inappropriately normal at 55 pg/ml. On the day of discharge, 25-OH-Vitamin D was 15 ng/dl, PTH 222 pg/ml and ionized calcium 1.07 mmol/L, when she was alert, oriented, with resolution of bone pains. Conclusion: Hypercalcemia in PHPT is from activation of osteoclasts and when these cells are inhibited by antiresorptive therapy, intestinal absorption will remain the primary source of plasma calcium levels. This explains the severe and prolonged hypocalcemia caused by Denosumab owing to its mechanism of action and long elimination half life, in our patient with Vitamin D deficiency on the background of malabsorption, despite a combination of primary and secondary elevation of PTH. Careful baseline assessment of calcium and Vitamin D levels, along with adequate supplementation and regular monitoring should be undertaken in all patients treated with Denosumab to avoid this.

Presentation: Saturday, June 17, 2023
SAT238 Ionophore-based Chemical Sensors For At-home Blood Calcium Monitoring
Authors: Ghanbari Ghalehjoughi Nasrin , Adil Nafesa , Wang Xuewei
Published: October 2023

Disclosure: N. Ghanbari Ghalehjoughi: None. N. Adil: None. X. Wang: None.

At-home blood calcium monitoring may revolutionize the management of hypoparathyroidism similarly as glucose meters have done for diabetes management. Measurements of ionized calcium in whole blood via ion-selective electrodes and total calcium in plasma via chromogenic probes have been routinely performed in hospitals for decades. However, calcium monitoring in resource-limited settings such as at home remains challenging. One reason is that large volumes of blood (> 95 μL) are needed for tests using current technologies, which are hard to collect from fingerpicks by patients. Another reason is that complicated and costly designs are used to handle fluids and perform on-site calibration. My group is developing two types of ionophore-based chemical sensors for highly selective detection of blood calcium via low-cost devices and less than 10 μL of capillary blood from the fingertip. In one direction, we develop highly sensitive colorimetric sensors that detect total calcium concentration in blood. Our novel biphasic sensing design does not suffer from optical interference from the colored and turbid blood and therefore tests blood without pretreatment processes. A smartphone with a color analysis app is used to acquire and analyze the colorimetric response to blood samples. In another direction, we develop electrochemical sensors that detect ionized calcium in blood without any fluid handling or on-site calibration. An innovative self-calibration method is designed to reduce the sensor-to-sensor variations and assure the accuracy of the calcium electrodes. The goal is that these methods will empower patients to self-monitor blood calcium and self-manage parathyroid disorders.

Presentation: Saturday, June 17, 2023
SAT253 A Rare Case Of Osteolytic Hypercalcemia Of Malignancy In Acute Myeloid Leukemia
Authors: Elahi Safiya , Baim Sanford
Published: October 2023

Disclosure: S. Elahi: None. S. Baim: None.

Introduction: Acute myeloid leukemia (AML) and other leukemias do not commonly induce hypercalcemia of malignancy (HCM). Limited previous reports of AML-related HCM have largely attributed cases to inflammatory-cytokine-mediated osteoclast activation, with rare reports of calcitriol-mediated HCM and ectopic parathyroid hormone (PTH) production. We describe an unusual case of AML-induced HCM caused by direct leukemic bone invasion, which responded to bisphosphonate therapy. Case Presentation: A 59-year-old female presented with spontaneous bruising and severe leukocytosis concerning for AML. The diagnosis was confirmed by flow cytometry and bone marrow biopsy. Imaging did not reveal any gross destructive bone lesions, but showed soft tissue nodules in the lumbar region which biopsy revealed to be myeloid sarcoma. Prior to initiation of chemotherapy, the patient developed severe hypercalcemia that was treated with aggressive intravenous hydration and zoledronic acid. Intrathecal chemotherapy and high-dose glucocorticoid therapy were initiated thereafter with normalization of serum calcium levels. PTH levels were suppressed. Calcitriol and PTHrP were below normal and undetectable, respectively. Bone turnover markers (C-telopeptide and bone-specific alkaline phosphatase) were significantly elevated prior to administration of zoledronic acid and normalized post-therapy. Calcium levels did not rebound after several interruptions in chemotherapy. Bone marrow biopsy showed focal areas of erosion in trabecular bone consistent with diffuse microscopic osteolytic disease. The patient developed bisphosphonate-induced hypocalcemia following treatment with zoledronic acid, which normalized with treatment with oral calcium carbonate. Discussion: Hypercalcemia of malignancy is a very unusual consequence of AML. No currently-published reports of this phenomenon have described biopsy-proven diffuse microscopic bone erosion associated with AML. We attribute our patient’s severe HCM to large-scale focal bone erosion by AML, independent of and/or associated with concurrent bone resorption mediated by inflammatory cytokines. A single dose of zoledronic acid, a potent suppressor of bone remodeling, achieved long term control of calcium for our patient despite interruption of chemotherapy. Bisphosphonate therapy should be considered an early treatment of HCM in patients with AML due to several potential mechanisms that result in direct calcium release from the skeleton.

Presentation: Saturday, June 17, 2023
SAT260 Asymptomatic Vitamin A Toxicity Causing Hypercalcemia
Authors: Seshan Nandini , Goswami Gayotri
Published: October 2023

Disclosure: N. Seshan: None. G. Goswami: None.

Background: Vitamin A toxicity is an overlooked cause of hypercalcemia. Most cases of hypercalcemia are secondary to primary hyperparathyroidism or malignancy. High levels of Vitamin A are thought to have a direct effect on the bone by stimulating osteoclast resorption or inhibiting osteoblastic formation, therefore increasing the fracture risk. Clinical Case: 56 year old female with history of alcoholic cirrhosis complicated by hepatic encephalopathy, acute kidney injury and now status post liver transplant five months prior that was admitted for asymptomatic hypercalcemia. Initially, hypercalcemia was thought to be secondary to cyclosporine, so medication was discontinued. Hypercalcemia resolved after hydration however she was again readmitted for hypercalcemia found on routine labs. She did not show any other signs of excess vitamin A. Lab work showed calcium 12.5 mg/dL (8.6 - 10.2mg/dL), albumin 4g/dL (3.4 - 4.8g/dL), normal 24 hour urine calcium excretion, eGFR 33mL/min, parathyroid hormone 16.9 pg/mL (8.7-77pg/mL), normal 1,25-OH and 25-OH vitamin D, PTHrP 25pmol/L, AM Cortisol 9mcg/dL, TSH 1.7 mIU/L (0.35 - 4.7mIU/L), serum protein electrophoresis unremarkable. Her vitamin A level was elevated to 113 ug/dL (30-75mcg/dL) and was diagnosed with hypercalcemia due to elevated vitamin A levels. Treatment involved hydration and discontinuation of her multivitamin containing vitamin A. Current limited literature suggests discontinuing vitamin A supplements will normalize vitamin A levels over time. Her vitamin A levels improved over several months. Incidentally, due to complaints of back aches from prior injury, imaging showed acute compression fracture deformities of two thoracic vertebrae. Bone density scan showed normal bone density. Bone turnover markers were elevated indicative of increased bone resorption. Clinical Lesson/Conclusion: Hypervitaminosis A is a rare etiology of hypercalcemia. Vitamin A toxicity may be due to excess ingestion of preformed vitamin A through supplements and animal sources. Though not well understood, the proposed mechanism of vitamin A actions on the bone involves stimulation of bone resorption through increase in osteoclastic activity and inhibition of bone formation through osteoblastic suppression, leading to high serum calcium and increasing the risk of fractures. We present a unique case in a patient who developed hypercalcemia secondary to hypervitaminosis A.

Presentation: Saturday, June 17, 2023
SAT261 Hypervitaminosis A With Hypercalcemia Without Overtly Excessive Vitamin A Intake
Authors: Chiou Cho-Yen , Greck Beth
Published: October 2023

Disclosure: C. Chiou: None. B. Greck: None.

Background: Hypervitaminosis A (hypervitA) is an uncommon cause of hypercalcemia and is due to excessive intake of preformed vitamin A (vitA), i.e., retinoids, especially in emulsified form, a common preparation in supplement. In contrast, provitamin (carotenoids) does not cause hypervitA due to limit in absorption and conversion to vitA. The tolerable upper intake level (UL) and recommended dietary allowance (RDA) of vitA for adult are 3000 and 700 (female) - 900 (male) mcg retinoid activity equivalent (RAE) respectively. While daily intake of vitA > UL carries risk of chronic toxicity, there are reports of hypervitA with chronic intake of vitA below UL. VitA is mainly stored in hepatic stellate cells (HSC). Liver injury can induce HSC to transform, releasing vitA, and losing capacity of vitA storage. Renal insufficiency is known with higher vitA levels in blood. Potentially, the threshold of vitA toxicity from supplement is much less in conditions with hepatic and/or renal disease. Here we report a case without history of excessive vitA intake developed hypervitA in relatively short period of time after hospitalization while in the acute and long-term care unit. Clinical Case: A 57-year male was hospitalized for alcohol related pancreatitis. It was complicated by sepsis, multi-organ failure requiring respirator, parenteral nutrition and/or tube feeding. Mild hypercalcemia was noted 4 weeks after admission, initially intermittently, then persistently and progressively higher, peak of 12.6 mg/dL at 4 months after admission. Prior calcium levels were low or normal up to 6 years before admission. Evaluation of hypercalcemia found low i-PTH, low 1,25-D, hypercalciuria, negative serum protein electrophoresis, and normal PTH-related protein. VitA was surprisingly elevated at 137 [38-98] mcg/dL. Nutritional intake was reviewed. No history of excessive vitA intake. Patient was on total parenteral nutrition (TPN) and/or tube feeding most of time, the range and average of daily preformed vitA supplement from admission to onset of hypercalcemia were 0-1309 and 1006 mcg RAE respectively; while from onset to peak of hypercalcemia, 0-3327 and 1891 mcg RAE respectively. The maximal daily preformed vitA via TPN is 1000 mcg RAE. All preformed vitA in tube feeding is from original formula without extra addition. After discovery of hypervitA, feeding formula was changed to one containing much less preformed vitA, and hypercalcemia slowly improved. Conclusion: HypervitA can develop relatively easily with tube feeding and/or parenteral nutrition with average daily preformed vitA above RDA but way below UL in a susceptible patient. In patients with liver disease and/or renal insufficiency, careful selection of feeding formula and/or nutritional supplement regarding content of preformed vitA, and alert to potential development of hypervitA are advisable.

Presentation: Saturday, June 17, 2023
THU597 Po2-guided Adrenal Vein Sampling In Primary Aldosteronism
Authors: Omata Kei , Tezuka Yuta , Ono Yoshikiyo , Satoh Fumitoshi
Published: October 2023

Disclosure: K. Omata: None. Y. Tezuka: None. Y. Ono: None. F. Satoh: None.

Background: Accurate laterality diagnosis of adrenal aldosterone over-secretion is crucial in determining specific treatment for primary aldosteronism. Although adrenal vein sampling (AVS) is considered as the gold standard method for lateralization, successful canulation to right adrenal vein (RAV) has been reported to be difficult since RAV usually empties directly into inferior vena cava (IVC). In addition, the entrance of RAV is close to that of hepatic vein (HV) or opens to a common trunk with HV in up to 20% of the patients with PA. Cortisol step-up and other proposed indices are not always available during the procedure. Method: AVS was performed in confirmed PA patients between January 2021 and March 2022 at Tohoku University Hospital. During AVS, a small portion (0.3mL) of the sampled veins (RAV, IVC and HV) were analyzed with a blood gas analyzer for partial pressure of oxygen (pO2) measurement. Result: A total of 113 AVS was performed. After excluding inappropriate samples, further analyzed were 113 samples of IVC, 100 of RAV, 109 of HV before cosyntropin stimulation, and 113 samples of IVC, 110 of RAV, 108 of HV after cosyntropin stimulation. We observed an average of 22 mmHg increase of pO2 in RAV than IPV, and 27 mmHg increase than HV before stimulation. The difference between RAV and IPV was 15 mmHg in average and that of RAV and HV was 21 mmHg after stimulation. Similar pO2 step-up was also observed between left adrenal vein and left inferior phrenic vein. Discussion: Here we first describe prominent pO2 step-up in both adrenal veins compared to neighboring non-adrenal veins and peripheral blood. pO2 measurement is easier, faster, less expensive, and requires a very small amount of sample, can be performed by routine equipments in angiography suite, compared to other selectivity indices of successful canulation in AVS. This could also contribute to reducing unnecessary blood sampling, radiation exposure and repeat AVS. pO2 step-up in adrenal vein suggests low oxygen consumption in adrenal glands, which potentially contributes to survival advantage in systemic hypoxic conditions. We propose the novel pO2-guided AVS especially in patients with difficult RAV anatomy and in unexperienced centers.

Presentation: Thursday, June 15, 2023
FRI087 Tuberous Xanthomas And Thrombocytopenia In A Patient With A New Diagnosis Of Sitosterolemia
Authors: Grigoryan Seda , Else Tobias
Published: October 2023

Disclosure: S. Grigoryan: None. T. Else: None.

Introduction/ Background: Sitosterolemia is a rare autosomal recessive disorder characterized by increased plasma sterol levels, that can lead to xanthomas, premature atherosclerosis, and hematologic abnormalities. It is most commonly caused by pathogenic variants in either ABCG5 or ABCG8 encoding sterol transporters that excrete sterols, leading to increased intestinal absorption and decreased biliary excretion of plan sterols. While patients with sitosterolemia have elevated LDL cholesterol levels, the pathophysiology of this process is still unclear. Clinical Case: A 46-year-old man presented with tuberous xanthomas and hyperlipidemia (HLD). In the past surgical removal had been attempted, but the lesions recurred. Prior labs: total cholesterol level was 235 mg/dL, triglycerides 85 mg/dL, HDL 61 mg/dL, LDL 157 mg/dL and mild thrombocytopenia (88 -127 K/uL) with giant platelets and anemia. Prior to the initial visit he started 40 mg atorvastatin with a subsequent increase to 80 mg daily.

Physical exam was notable for periocular xanthelasmas and tuberous xanthomas. Achilles tendons appeared thickened without nodules. There was no family history of premature cardiac disease. Initial labs: Total cholesterol was 206 mg/dL(ref 120-200 mg/dL), TG mg/dL 66 mg/dl (ref 40-200mg/dL), LDL 119 mg/dL (ref 70-130 mg/dL), HDL 62 mg/dL (ref >40), platelets 111 K/uL (ref 150-400 K/uL) with 27.7% immature fraction, Hb 13.6 g/dL (13.5-17 g/dL). Plasma sterols were significantly elevated, campesterol 182.2 mg/L (ref <8mg/L), cholestanol 20.6 mg/L (ref <6 mg/L ), sitosterol 247.2 mg/L (ref <15mg/L ), stigmasterol 11.5 mg/L (ref <0.5 mg/L), indicative of a diagnosis of sitosterolemia. Coronary artery calcification (CAC) revealed a score of 15 which represents 50-75th percentile for age and gender, indicating CAD disease in the patient. Following the diagnosis of sitosterolemia, the patient started ezetimibe 10 mg daily, atorvastatin was decreased to 40 mg daily given the success at decreasing the LDL. Follow up LDL decreased to 58 mg/dL (48% decrease) and non-HLD to 71 mg/dL (53% decrease). Patient was counseled on dietary modification with a focus on avoidance of plant-based oils as well as referred to medical genetics and a dietician for more in-depth counseling. Genetic confirmation is pending. Conclusion: The global prevalence is estimated to be 1/1,000,000∼5,000,000. However, prevalence is likely underestimated due to the significant clinical and biochemical overlap with other hyperlipidemias and great variations in phenotype. Due to the differences in treatment and dietary counseling, it is important to consider this diagnosis, particularly in patients with typical concurrent hematological abnormalities.

Presentation: Friday, June 16, 2023
FRI098 Triglyceride Glucose Index Is Associated With Elevated Blood Pressure, Independent Of Body Mass Index: Analysis From NHANES Study
Authors: Ayesh Hazem , Dean Niswender Kevin
Published: October 2023

Disclosure: H. Ayesh: None. K.D. Niswender: None.

Introduction: Triglyceride glucose index (TyG) is a novel marker of insulin resistance. Elevated blood pressure is associated with significant morbidity and mortality. Early identification of individuals at-risk for cardiovascular disease is essential for effective prevention. There are multiple reports in the literature that triglyceride glucose index (TyG), is associated with elevated blood pressure. In this study, we determined the association of TyG with elevated blood pressure, independent of body mass index (BMI), age, and diabetes status. Methods: A sample of 6799 individuals from the NHANES study population (2011-2020) consisting of all individuals who are above 18 years of age and have serum glucose and serum triglyceride levels available to calculate TyG. Elevated blood pressure status was assigned based on the question“Ever told you had high blood pressure” from NHANES survey.”. TyG was calculated using the formula “ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2]”. TyG values were divided into 4 quartiles as follow: 1st(<4.36), 2nd (< 4.56), 3rd(< 4.77), 4th(> 4.77). Logistic regression analysis was performed to assess the association between TyG and elevated blood pressure. The analysis was adjusted for age, BMI, and diabetes status. Results: The analysis revealed a significant association between elevated blood pressure and TyG independent of age, BMI and diabetes status. The odds of elevated blood pressure were higher in the 4th quartile TyG compared to the 1st quartile with an odds ratio of 1.39 (95% CI 1.21-1.59), P value < 0.001. Discussion/Conclusion: These results indicate that TyG can serve as a screening tool to identify individuals at risk for elevated blood pressure. Serum triglyceride and glucose measurement are affordable and routine in clinical practice. Implementation of auto-calculation of TyG based on serum triglyceride and glucose values in electronic health records may provide helpful screening and monitoring tools to identify individuals at risk for elevated blood pressure, especially with normal BMI. Future high-quality prospective studies will be helpful to further understand the association.

Presentation: Friday, June 16, 2023
FRI107 Ketogenic Diet Prevents Development Of Atherosclerotic Plaques In Apolipoprotein E Knockout Mice
Authors: Marzolla Vincenzo , Armani Andrea , Mammi Caterina , Gorini Stefania , Camajani Elisabetta , Caprio Massimiliano
Published: October 2023

Disclosure: V. Marzolla: None. A. Armani: None. C. Mammi: None. S. Gorini: None. E. Camajani: None. M. Caprio: None.

Higher aldosterone (aldo) levels are associated with increased risk of cardiovascular ischemic events and mortality. It has been demonstrated that aldo accelerates the development of atherosclerosis in apolipoprotein E knockout mice (ApoE KO). Ketogenic diet (KD) positively impacts several cardiovascular risk factors, yet its effect on atherosclerosis is elusive. We hypothesize that KD protects from development of atherosclerotic plaques in ApoE KO mice, a murine model of atherosclerosis. Eight-week-old male ApoE KO mice were fed a KD (90,5% Kcal from fat, 0.4% Kcal from carbohydrate, 9.1% Kcal from protein) or a moderate high fat die (HFD) (42% Kcal from fat, 42.7% Kcal from carbohydrate, 15.2% Kcal from protein) and treated with aldosterone (aldo, 6 μg/mouse per day) or vehicle through osmotic mini-pumps. Cholesterol content was comparable in KD and HFD. After 4 weeks of treatment, in all experimental groups, intraperitoneal glucose tolerance test was performed, and peripheral blood samples were collected. We analysed cryosections of embedded aortic root to quantify the atherosclerotic plaque size, lipid and collagen content. We assessed vascular inflammation in speciments of thoracic aorta by analysing pro-inflammatory (ICAM-1, VCAM-1, IL-6, TNF-α, MCP-1) and anti-inflammatory (Arg-1, RETNLA, CCL5) genes. In ApoE KO mice treated with aldo, KD determined a significant improvement in glucose tolerance, compared to mice fed a HFD, without any significant effect on body weight. Beta-hydroxybutyrate levels were always significantly higher in KD-mice than in AD-mice, confirming nutritional ketosis in KD-mice. Analysis of aortic root showed that aldo treatment determined a significant increase in atherosclerotic plaque size and lipid content in HFD-mice. Such effects were significantly reduced in KD-mice, suggesting a favorable impact of ketosis in preventing atherosclerosis development. Plaque fibrosis did not differ among treatment groups. Finally, we observed a significant reduction in vascular inflammatory markers in KD-mice, when compared to HFD-mice. In particular, KD determined a significant reduction in gene expression of pro-inflammatory markers (ICAM-1, VCAM-1, IL-6, TNF-α, MCP-1) with the concomitant up-regulation of anti-inflammatory markers (Arg-1, RETNLA, CCL5), compared to HFD. The study suggests KD as a potential non-pharmacological approach to prevent the development of atherosclerotic disease in subjects with high cardiovascular risk.

Presentation: Friday, June 16, 2023
FRI113 Increased Body Fat Is Associated With Heart Failure Of Ischemic Cause
Authors: Bandeira Francisco , Oliveira Lucian B , Siqueira Mariana A F M , Gadelha Rafael B M , Correia Alice R P , Garcia Jessica M A , Victor Bandeira Francisco , Paula Bandeira Maria
Published: October 2023

Disclosure: F. Bandeira: None. L.B. Oliveira: None. M.A. Siqueira: None. R.B. Gadelha: None. A.R. Correia: None. J.M. Garcia: None. F.V. Bandeira: None. M.P. Bandeira: None.

Introduction: Adiposopathy is a relevant cardiovascular risk factor, being related to the onset of endothelial dysfunction and atherosclerotic disease, and has also been identified as a factor that may contribute to the onset or progression of heart failure (HF). Objective: To evaluate percent body fat (%BF) in patients hospitalized for HF and its relationship with cardiometabolic parameters and with HF etiology. Methods: Cross-sectional study was conducted in a Cardiology center, with patients aged 40 to 64 years hospitalized with HF. %BF was assessed by whole-body dual-energy x-ray absorptiometry (DXA), using the cutpoint of 25% for men or 35% for women. Coronary ischemia was confirmed by imaging tests or coronary angiograms. Results: A total of 109 patients were evaluated, of which 50.5% were female. The medians of age, length of hospital stay and left ventricular ejection fraction (LVEF) were 58 years (interquartile range [IQR] 53-61), 20 days (11-32) and 48% (34-60), respectively. 48.6% had preserved LVEF (≥50%), 11.0% mildly reduced LVEF (41-49%), and 40.4% reduced LVEF (≤40%). According to the New York Heart Association Functional Classification (NYHA-FC), 33% had NYHA-FC I-II and 67% NYHA-FC III-IV. Most patients had dysglycemia (32.1% prediabetes and 57.7% diabetes; hemoglobin A1c [HbA1c] median: 6.4% [5.8-8.4]). HF of ischemic cause was present in 57.8% of the patients. High %BF was present in 67.9%, while body mass index (BMI) in the obesity range was observed in 41.3%. High %BF was associated with ischemic HF (77.8% high %BF in ischemic HF vs. 54.3% in non-ischemic HF, p=0.010). Ischemic etiology was also associated with higher BMI (29.4 ± 5.0 vs. 26.8 ± 5.6 kg/m², p=0.012). %BF was not associated with gender (67.3% of women vs. 68.5% of men, p=0.889) or NYHA-FC (75.0% of those with NYHA-FC I-II vs. 64.4% of those with NYHA-FC III-IV, p=0.264). It was associated with higher LVEF (50.5% [36.8-62.0] vs. 37.0% [27.0-59.0], p=0.023), shorter hospital stays (18.0 [9.3-28.0] vs. 24.0 days [13.0-35.0], p=0.028), and higher serum triglycerides (139.0 [98.8-199.3] vs. 91.0 mg/dL [70.0-140.0], p=0.001). There were no associations between high %BF and HDL-cholesterol (35.0 [26.8-45.3] vs. 37.0 mg/dL [29.3-47.9], p=0.601), total cholesterol (166.0 [139.0-189.3] vs. 164.0 mg/dL [129.0-193.5], p=0.594) or HbA1c levels (6.25% [5.8-8.4] vs. 6.5% [5.6-8.7], p=0.990). Conclusion: Our data demonstrated larger increases in body fat from patients admitted with HF of ischemic cause, which was associated with shorter hospital stay and higher serum triglycerides concentrations.

Presentation: Friday, June 16, 2023
FRI153 Genetic Variant In Armadillo Repeat Containing 5 Gene (ARMC5) Associates With Salt Sensitivity Of Blood Pressure And Aldosterone In A Caucasian Cohort
Authors: Parksook Wasita W , Heydarpour Mahyar , Pojoga Luminita , Gaye Amadou , Gibbons Gary H , Williams Gordon H , Williams Jonathan S
Published: October 2023

Disclosure: W.W. Parksook: None. M. Heydarpour: None. L. Pojoga: None. A. Gaye: None. G.H. Gibbons: None. G.H. Williams: Advisory Board Member; Self; Cereno. Consulting Fee; Self; Alnylam, Crinetics, Damian, KBP bioscience, Paxel, Relapsa, Unicycive. Grant Recipient; Self; NIH 2 grants. J.S. Williams: Advisory Board Member; Self; Mellicell, Inc.

Background: Genetic alterations of ARMC5 have been reported in various adrenal disorders, particularly in primary bilateral macronodular adrenal hyperplasia. Increasing evidence shows that polymorphic variants in ARMC5 are also associated with blood pressure (BP), hypertension, and the renin-angiotensin-aldosterone-system (RAAS) in individuals of African descent; however, little is known about these relationships in Caucasians. Herein, we conducted a deep phenotyping study to assess the association of ARMC5 variants with BP, salt sensitivity of BP (SSBP), and components of the RAAS in Caucasians. Methods: Normotensive and hypertensive, non-diabetic, non-chronic kidney disease, Caucasian participants underwent two dietary interventions at 5-7 days apart (200 mmol/day and 10 mmol/day sodium) to assess SSBP and other hormonal parameters. All participants were genotyped using a Multi-Ethnic-Genotyping-Array. Association analysis and the quality control of the genomic data were assessed by PLINK. Participants with complete data for SSBP and hormonal parameters, who were in salt balance, were included in the analysis (n= 306). Multiple linear regression models were used to assess the association between the genetic variant and outcome parameters. Results: There were 5 single nucleotide polymorphisms in the ARMC5 region. rs4889660 was significantly associated with SSBP in additive and dominant models when adjusted by Bonferroni correction. In a candidate gene analysis, rs4889660 risk allele carriers had greater SSBP than non-risk allele homozygotes (β= 4 mmHg, P= 0.03). Following dietary sodium restriction, rs4889660 risk allele carriers had lower serum aldosterone levels in an upright position (β= -6.9 ng/dl, P= 0.04) and serum aldosterone levels after angiotensin II stimulation (β= -3.0 ng/dl, P= 0.02). There were no differences between plasma renin activity, serum and urinary cortisol levels, and renal plasma flows between genotypes. Conclusions: There was an association between the ARMC5 rs4889660 variant and SSBP in Caucasians. With dietary sodium restriction, aldosterone responses to both upright posture and angiotensin II infusion were lower in the risk allele carriers. The reduced aldosterone responses suggest that an alteration in the RAAS system is not the cause of the SSBP, but is in response to a defect in another sodium-mediated homeostatic mechanism.

Presentation: Friday, June 16, 2023
THU247 Characterizing Inpatient Cases Of DKA Precipitated By SGLT2 Inhibitor Use
Authors: Aslamy Arianne , Nazemi Reza , Tseng Conrad , Kim Steve , Gianchandani Roma
Published: October 2023

Disclosure: A. Aslamy: None. R. Nazemi: Speaker; Self; Eli Lilly & Company, AstraZeneca. C. Tseng: None. S. Kim: None. R. Gianchandani: None.

Background: SGLT2 inhibitors are a unique class of anti-hyperglycemic medications that can increase the risk of DKA in patients with diabetes (1). The overall incidence of DKA precipitated by SGLT2 inhibitor use is estimated to be 0.1%, however, this is likely higher in practice with increasing usage of these medications for treatment of heart failure and renal dysfunction. Herein, we characterize inpatient admissions with SGLT2 inhibitor induced DKA to further understand associated risk factors. Clinical Case: Euglycemic and hyperglycemic DKA cases (n=7) over a four-month period were identified, all of whom had been on SGLT2 inhibitors for an average of 8.5 (± 5.4) months prior to presentation. Six patients had T2D and one patient had known T1D. The average patient age was 69 (±8) years. The average A1c was 9.2% (±1.9%). Patients on dapagliflozin (n=3) had significantly higher A1c on admission compared to those on empagliflozin (n=4) (p=0.017). Average glucose on presentation of the six T2D patients was 206.5 (± 55.61) mg/dL (euglycemic DKA range) while the T1D patient presented with glucose of 605 mg/dL. All seven patients had elevated anion gap (mean 25.5 ± 7.2mEq/L), low bicarbonate (mean 8.9 ± 4.1 mmol/L), pH less than 7.4, and evidence of either ketonemia or ketonuria. Five out of the seven cases had a concurrent infection, and the remaining two cases were readmissions after recent cardiac surgery. All patients were treated with intravenous/subcutaneous insulin and intravenous dextrose with resolution of DKA within 24 hours. SGLT2 inhibitors were immediately discontinued. Average length of stay was 9 (±6) days, and was higher in the postcardiac surgery patients. Notably, the type of SGLT2 inhibitor (dapagliflozin vs. empagliflozin), age, sex, A1c on presentation, number of comorbidities, presence of infection, prior insulin usage, duration of diabetes, and duration of SGLT2 use had no significant effect on length of stay. Conclusion: Clinical characteristics of SGLT2 inhibitor induced DKA cohort were older age, uncontrolled diabetes (A1c >7), and concurrent infections or recent major surgery. Resolution of DKA was quick and length of stay longer for major surgery. When placed on SGLT2 inhibitors, diabetes patients should be warned of these potential clinical scenarios that can increase their risk of DKA. Reference: (1) Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data. Diabetes Metab Res Rev. 2017 Nov; 33

Presentation: Thursday, June 15, 2023
THU249 Use Of The Pittsburgh Sleep Quality Index In People WithT2DM: Initial Results Of The Diabetes Sleep Assessment (DSA) Study
Authors: Shaikh Shehla , Shaikh Salomi , Shaikh Shayaan , Shaikh Asma , Shaikh Mehvish , Memon Zaid , Sayed Rainah
Published: October 2023

Disclosure: S. Shaikh: None. S. Shaikh: None. S. Shaikh: None. A. Shaikh: None. M. Shaikh: None. Z. Memon: None. R. Sayed: None.

Background: The Pittsburgh Sleep Quality Index (PSQI) is a well-known, validated, and reliable instrument used to measure the clinical construct of sleep quality. PSQI > 5 indicates poor sleep quality. Aim: To evaluate PSQI for psychometric properties through glycemic and anthropometric parameters, in T2DM who are on regular follow-up for glycemic care Method: We examined 236 known T2DM in the Diabetes Sleep Assessment (DSA) study, an ongoing observational study examining the effect of control of diabetes and metabolic parameters on the quality of sleep Results: The glycemic and anthropometric parameters were age 55 years (±11, 95% CI 53 to 56), BMI 28 kg/m2 (±5.8, 95% CI 28 to 29), FPG 140 mg/dl (±50, 95% CI 134 to 147), PPG 197 mg/dl (±76, 95% CI 188 to 207), HbA1c 7.4% (±1.2, 95% CI 7.1 to 7.6), duration of diabetes 9.2 years (±, 7.5 95% CI 8.3 to 10), neck circumference 36 cm (±6.2, 95% CI 36 to 37), waist circumference 117 cm (±17, 95% CI 114 to 119). 76.2% (n=180) had PSQI >5. The mean PSQI was 8.3 (±3.7, minimum 0, maximum 19, 95% CI 7.8. to 8.8). No significant correlation was found between PSQI and glycemic and anthropometric parameters. The greatest dysfunction (>3 component score) was reported to get up to go to the bathroom by 66.9% (n=158), followed by waking up in the middle of the night or early morning by 49.1% (n=116). The median time to go to bed and wake in the morning was 11 pm and 7 am, respectively. The median no. of hours to fall asleep, for actual sleep and in bed were 1, 6.5, and 8, respectively. Mean PSQI in the group with inadequate glycemic control (HbA1c >7, n=130), was 8.4 (±3.9) as compared to the group with adequate glycemic control (HbA1c ≤7, n=106), which had a mean PSQI 8.1 (±3.5), was comparable, p=0.56 (ns). Conclusion: Our results reveal that the anthropometric parameters have no significant impact on the quality of sleep and are independent of the glycemic control in T2DM. The need to go to the bathroom at night and wake up in the night or early morning were the largest contributors to the poor quality of sleep. The result of our study needs large-scale, multi-centric collaboration to further address the gaps and challenges to improve the quality of sleep in T2DM

Presentation: Thursday, June 15, 2023
THU255 Tirzepatide-induced Weight Loss In A Type 2 Diabetic Taking Oral Contraceptives
Authors: Arunachalam Amar , Nguyen Andy , Shah Neel L
Published: October 2023

Disclosure: A. Arunachalam: None. A. Nguyen: None. N.L. Shah: None.

Obesity is a global health challenge which can lead to type 2 diabetes, hypertension, cardiovascular disease, and decreased life expectancy. In addition to lifestyle intervention, pharmacotherapy to sustain weight loss has remained limited due to effectiveness, cost, and adverse effects. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like-peptide-1 receptor agonist currently approved for type 2 diabetes treatment. Tirzepatide-induced weight loss may provide new options for treatment of obesity. We report a 32-year-old female with a history of T2DM and PCOS originally on metformin who was started on semaglutide 0.25 mg, which was uptitrated to 0.5mg weekly for 6 months. She lost 25 lbs with no side effects. Semaglutide and OCPs were discontinued due to fertility with her weight and hemoglobin A1C rebounding off medication. She was started on tirzepatide 2.5mg weekly. At that time, she weighed 223 lbs with a hemoglobin A1C 8.2%. She was counseled to resume OCPs and improve glucose control and weight reduction prior to attempting to conceive. Once increased tirzepatide dosing to 5mg weekly, she endorsed severe nausea and intermittent epigastric abdominal pain on day of injection. She attempted to increase dose to 7.5mg weekly, but dose was reduced due to complaints of constipation and worsened abdominal pain requiring bowel regimen. She remained on tirzepatide for a total of 4 months prior to becoming pregnant while on oral contraceptives. Her weight decreased from 223 to 212 lbs with reduction in hemoglobin A1C from 8.2% to 6.1%. While initially studied for use in type 2 diabetes, tirzepatide was found to induce clinically significant weight reduction. The recent SURMOUNT-1 trial, which studied the effects of tirzepatide in non-diabetics, demonstrated that once-weekly tirzepatide at three different doses demonstrated substantial and sustained weight reduction in patients with obesity. In trials involving patients with once-weekly injectable semaglutide, the mean reduction in hemoglobin A1C was 1.8 percentage points and reduction in mean body weight was 6.5 kg. In the SURPASS-2 trial, reductions in body weight were greater with tirzepatide when compared to semaglutide with mean estimated treatment difference −1.9kg, -3.6kg, and -5.5 kg respectively based on dosing of 5mg, 10mg, and 15mg. The adverse events most commonly reported in patients on tirzepatide include nausea, vomiting, and diarrhea, which occurred most commonly during dose-escalation. Mounjaro is known to reduce the efficacy of oral contraceptive pills due to delayed gastric emptying. This delay is largest after the first dose so recommended to switch from oral to non-oral contraceptives for the first four weeks when tirzepatide is initiated. It is important to counsel patients on the decreased efficacy of oral contraceptives while on tirzepatide.

Presentation: Thursday, June 15, 2023
THU258 Development Of A Clinical Dataset For Artificial Intelligence: A 30-Year Journey
Authors: Ramachandra Gumpeny Sridhar , Gumpeny Lakshmi
Published: October 2023

Disclosure: S.R. Gumpeny: None. L. Gumpeny: None.

Deep learning requires clean and machine-readable data for analysis. Currently there is a mismatch between the availability of accessible clinical data and the development of predictive modeling employing artificial intelligence. The scarcity is particularly acute in India. We describe the construction and evolution of electronic medical records (EMR) in an Endocrine Centre in India. December 1992 marked the end of paper documents at EDC, India. Ever since all records were stored as electronic medical records (EMR). Digitization was preceded by an analysis of work flow to ensure harmonious interaction between patient encounter and capture of data. Over years the EMR evolved across databases and was refined to improve ease of use. Rule based diagnoses, prescriptions, diet advice and auto-calculations were incorporated. Eventually it was set up on a networked platform to allow biographic, lab and anthropometric data to be entered before the patient came to the consultation chamber. Currently, the database has 90,000 individual records, including follow up data of patients with different endocrine disorders. We are at the cusp of linking the EMR with wearable sensors to make it more comprehensive. It is ripe to serve as a platform for deep learning, predictive modelling and artificial intelligence. Account sof its construction, as well as the potential for using AI in clinical care have been documented

References: (1). Sridhar GR. Expanding scope of information technology in clinical care. IGI Global. DOI: 10.4018/978-1-13479-3.ch131. (2) Sridhar GR, Lakshmi G. Artificial intelligence in medicine: diabetes as a model. In (Eds) Srinivasa KG et al. Artificial Intelligence for Information management: A healthcare perspective. Studies in Big Data 88. Doi.org/10.1007/978-981-16-0415-7_14

Presentation: Thursday, June 15, 2023
THU260 Development Of Plantar Thermography For Screening Of Diabetic Neuropathy
Authors: Panamonta Vipawee , Jerawatana Ratanaporn , Ariyaprayoon Prapai , Looareesuwan Panu , Ongphiphadhanakul Benyapa , Sriphrapradang Chutintorn , Ongphiphadhanakul Boonsong
Published: October 2023

Disclosure: V. Panamonta: None. R. Jerawatana: None. P. Ariyaprayoon: None. P. Looareesuwan: None. B. Ongphiphadhanakul: None. C. Sriphrapradang: None. B. Ongphiphadhanakul: None.

Background: Diabetic foot ulcers are a major complication of diabetes. They are also the leading cause of nontraumatic lower extremity amputation. The incidence of diabetic foot ulcers is highest in those patients with poor glycemic control and neuropathy. In people with diabetic neuropathy, the feet temperature may change due to decreased blood flow and nerve damage. Thermography has been proposed as a noninvasive modality to identify patients at risk for diabetic foot ulcers. In this study, we used thermography and deep learning to stratify patients with diabetes at risk for developing a foot ulcer. Methods: We prospectively record clinical data and plantar thermogram in adult diabetic patients underwent diabetic foot screening at outpatient clinics at Ramathibodi hospital, Bangkok, Thailand during September to December 2022. Altogether, there were 245 thermal images were analyzed using a deep learning algorithm to determine the risk for diabetic foot ulcers by transfer learning using the pre-trained VGG16 model which is a convolutional neural network for image recognition. Twenty percent of the images were set aside for testing purposes while 20% of the images served as the validation set during training of the neural network. The neural network was trained and weighed more toward higher sensitivity of identifying at risk feet for screening purpose. Results: The study sample consisted of individuals with a mean age of 62.5±12.5 years, 57.1% who had diabetes for more than 10 years. The majority of the participants were females (57.1%). The average body mass index (BMI) was 27.8±9.6 (kg/m2). There were 186 thermal images classified as category 0 and 59 images classified as categories 1 to 3 according to the American Diabetes Association risk classification. The trained neural network achieved 75 % accuracy with 95 % sensitivity and 67 % specificity for classifying thermograms as higher than normal risk in the training dataset. For the testing dataset, the sensitivity and specificity was 75% and 41%, respectively. The accuracy, however, decreased to 50% due mainly to the misclassification of normal thermograms from abnormal. Conclusions: These results suggest that thermography combined with deep learning could potentially be developed for screening purpose to stratify patients at risk of developing diabetic foot ulcers. Further research is needed to validate the results in larger datasets and to explore alternative algorithms for predicting diabetic foot ulcers.

Presentation: Thursday, June 15, 2023