bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Glycemic Variability Predicts Adverse Outcomes in Diabetic Heart Failure With Preserved Ejection Fraction
Authors: Hsu Jung-Chi , Yang Yen-Yun , Chuang Shu-Lin , Lin Lian-Yu
Published: October 2024

Context

Previous studies have shown associations between glycemic variability (GV) and cardiovascular outcomes in patients with type 2 diabetes. However, the effect of GV on outcomes in diabetic patients with heart failure with preserved ejection fraction (HFpEF) has not been investigated.

Objective

To investigate the association between increased GV and cardiovascular outcomes in diabetic patients with HFpEF.

Methods

Between 2014 and 2019, we conducted a retrospective cohort analysis using the electronic medical records of a tertiary medical center in Taiwan. Diabetic patients with HFpEF were enrolled. Each individual's coefficient of variability of fasting glucose (FGCV) was determined and the FGCVs were categorized into tertiles. Multivariable Cox regression models and the Kaplan-Meier with log-rank test were used to assess the association between the FGCV and the risk of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiovascular mortality, and overall mortality.

Results

In a cohort comprising 74 835 individuals diagnosed with diabetes, a subset of 753 patients was identified with HFpEF and measurement of FGCV. The median follow-up duration was 38.1 months. In the model of full adjustment, the third FGCV tertile was statistically significantly associated with an increased risk of HHF compared to the first tertile (hazard ratio [HR] = 1.32; 95% CI, 1.04-1.69; P = .025). Likewise, the highest FGCV tertile was associated with an increased risk of death (HR 1.65; 95% CI, 1.16-2.35; P = .005), whereas it was not associated with increased of AF and cardiovascular mortality. Kaplan-Meier analyses revealed a statistically significant association between FGCV and both HHF and overall mortality (log-rank P = .022 and <.001, respectively).

Conclusion

Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an elevated overall mortality rate in individuals with diabetes and HFpEF.
7530 Monoacylglycerol metabolism in adipose tissue macrophages
Authors: Mooring A , Park M y , Bruno J , Aleman Diaz J O
Published: October 2024

Disclosure: A. Mooring: None. M. Park: None. J. Bruno: None. J.O. Aleman Diaz: None.

White adipose tissue is a heterogeneous organ that is comprised of multiple cell types including adipocytes, nerve cells, endothelial cells and immune cells, each of which are important contributors to adipose tissue homeostasis. Adipose tissue macrophages (ATMs) are key regulators of local and systemic inflammation, adipocyte differentiation and extracellular lipid accumulation. Recent studies evaluating the lipidomic profile of extracellular vesicles (EV) released from adipocytes indicate an association between specific lipid species in EVs and metabolic dysfunction. Individual lipid species influence the crosstalk that occurs between adipocytes and ATMs indicating them as potential molecular messengers. LC-MS analysis performed in our lab has identified monoacylglycerols (MAGs) as the most abundant lipid species in human primary ATMs. However, the role of MAGs in the communication between adipocytes and ATMs remains unclear. To investigate the impact of MAGs on ATMs, we cultured mouse-derived J774.A1 macrophages and treated them with varying concentrations of MAGs (5µM, 50µM, 500µM, 5mM, or 50mM) for 24 hours. We observed significant intracellular lipid accumulation via a targeted LC-MS approach.When MAGs were added to the J774.A1 cell line at a concentration of at least 5mM compared to untreated cells. To further explore this, we employed confocal microscopy to qualitatively assess differences in lipid localization in these cells. We treated an additional cell culture with 50mM of triacylglycerol (TAG) as a control. As anticipated, the cells stored the TAG as lipid droplets. In contrast, cells treated with MAG displayed a dispersed cytosolic storage pattern for the lipid. These findings indicate that the J774.A1 cell line actively stores MAG differently compared to TG. To correlate our cellular findings in human tissues, MALDI imaging was conducted on sections of human visceral adipose tissue. Our in-situ analyses showed spatial anti-correlation between monoglycerides (MAG 20:2, MAG22:2, MAG20:3, MAG 22:3) and triglycerides (TAG 46:9 and TAG 50:8), indicating a distinct location of MAGs within adipose tissue. Our findings provide insights into the accumulation of this neutral lipid within ATMs, as well as its spatial distribution in human tissues. Leveraging these insights may contribute to the development of targeted therapies to mitigate the metabolic complications associated with excess weight.

Presentation: 6/1/2024
7122 Obesity is associated with lower basal state cortisol, and diminished cortisol response to the low dose 1ug ACTH: time to depart from the obesity/pseudo-Cushing myth
Authors: Sofer Yael , Osher Esther , Greenman Yona , Michele Tordjman Karen , Shenkerman Galina , Yaron Marianna , Marcus-Perlman Yonit , Moshe Yaffa , Shaklai Sigal , Limor Rona , abiri shirly , Cantrell Dror , Stern Naftali
Published: October 2024

Disclosure: Y. Sofer: None. E. Osher: None. Y. Greenman: None. K.M. Tordjman: None. G. Shenkerman: None. M. Yaron: None. Y. Marcus-Perlman: None. Y. Moshe: None. S. Shaklai: None. R. Limor: None. S. abiri: None. D. Cantrell: None. N. Stern: None.

Objective: Some clinical resemblance may exist between obesity, particularly abdominal obesity, and Cushing’s syndrome. This has stimulated ongoing interest in the role of cortisol's secretion pattern, control and metabolism in obesity. Goals: To compare basal and dynamic cortisol response to an intravenous bolus dose of 1 ug ACTH in healthy obese versus lean controlsDesign: Total, free and salivary cortisol were tested at the basal state and after a standard challenge with 1 ug ACTH in 60 healthy obese subjects (mean BMI= 39 kg/m2) and 54 healthy lean controls (mean BMI=23 kg/m2). Results: Basal total cortisol was significantly lower in obese as compared to lean subjects [361.56+/-132 vs 414+/- 121 nmol/L; p=0.019]. Additionally, baseline total cortisol and salivary cortisol were inversely related to BMI (r=-0.24, r=-0.27; p<0.05 for both). Baseline total and salivery cortisol were also negatively correlated with waist circumference (r=-0.27, r= -0.34; p<0.05 for both). Upon challenge with ACTH, total and salivary cortisol response were significantly lower in obese than in lean subjects [665.16+/-151.8 vs. 728.64+/- 124.2 nmol/L, p<0.05; 31.66 (19-38.64) vs. 40.05 (31.46-46.64) nmol/L, p<0.05]. Conclusion: Basal as well as peak stimulated cortisol and integrated post-1ug ACTH-stimulated total serum cortisol levels were significantly lower in obese subjects. Obesity is not associated with enhanced basal cortisol or ACTH-stimulated cortisol reserve. Hence, increased serum or salivary cortisol is atypical for uncomplicated obesity.

Presentation: 6/1/2024
6851 Rapidly Increasing Use of Anti-Obesity Medications among Veterans in the Veterans Health Administration (VA)
Authors: Vimalananda Varsha , Qian Shirley , Bolton Rendelle , Hung Anna , Smith Valerie , Maciejewski Matthew
Published: October 2024

Disclosure: V. Vimalananda: None. S. Qian: None. R. Bolton: None. A. Hung: None. V. Smith: None. M. Maciejewski: None.

Introduction: Obesity is a prevalent and costly chronic disease that compromises quality of life; increases risks of cardiometabolic disease, osteoarthritis, and several cancers; and accounts for 28% of U.S. health care costs. Anti-obesity medications (AOMs) may fill the treatment gap given the low uptake of bariatric surgery and limited effectiveness of behavioral interventions, and are guideline-recommended as part of a comprehensive obesity treatment plan. The landscape for obesity treatment has changed with introduction of the highly effective and in-demand glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1 + GIP receptor agonists (GIP/GLP-1 RAs). Given limited knowledge of use patterns, we describe use of AOMs among patients receiving care in the Veterans Health Administration (VA), which is the largest integrated health system in the United States. Methods: In a retrospective cohort study of VA patients from 7/1/2021-6/30/2023, we examined data from the VHA Corporate Data Warehouse separately for patients on AOMs without and with diagnosed diabetes, since the newer AOMs can be used at lower doses for the diabetes indication. Results: There were 31,106 patients without diabetes and at least one AOM prescription in the two year study period, who were 60% male and 62% White. AOM prescriptions from Year 1 to Year 2 among this group increased 215%. Overall, prescriptions were: semaglutide 34%, liraglutide 18%, orlistat 18%, phentermine/topiramate 14%, bupropion/naltrexone 12%, phentermine 4% and tirzepatide 0.03%. Prescribers were physicians 60%, LIPs 25%, and pharmacists 13%. There were 188,017 patients with diagnosed diabetes and at least one AOM prescription, and they were 92% male and 67% white. AOM prescriptions from Year 1 to Year 2 among this group increased 14% and were primarily (87%) for semaglutide. Prescribers were physicians 63%, licensed independent practitioners (LIPs) 23%, and pharmacists 10%. Conclusions AOM use is increasing in VA across all AOM classes, particularly among patients without diabetes, indicating growing interest in medical treatment of obesity. As AOM use spreads, real-world evidence on weight loss and clinical outcomes is needed among patients like those in VA who tend to be older and less healthy than the highly selected patients included in randomized clinical trials. Data is especially needed to guide practice among patients with obesity and without diabetes, given the dramatic increase in use among that group over the past 2 years.

Presentation: 6/1/2024
7279 Survodutide and Semaglutide Both Induce Weight Loss but Show Different Effects on Food Preference and Dyslipidemia in the Free Choice Diet-induced Obese Hamster Model
Authors: Briand F , Augustin R , Bleymehl K , Zimmermann T , Klöckener T , Klein T
Published: October 2024

Disclosure: F. Briand: Employee; Self; Physiogenix. R. Augustin: Employee; Self; Boehringer Ingelheim. K. Bleymehl: Employee; Self; Boehringer Ingelheim. T. Zimmermann: Employee; Self; Boehringer Ingelheim. T. Klöckener: Employee; Self; Boehringer Ingelheim. T. Klein: Employee; Self; Boehringer Ingelheim.

Introduction: Semaglutide, a GLP-1 receptor agonist, and survodutide, a GCGR/GLP-1R dual agonist, have demonstrated significant weight loss in patients with obesity. To test whether this weight loss is associated with changes in food preference and improvement in dyslipidemia, we evaluated semaglutide and survodutide in the free choice diet-induced obese and dyslipidemic hamster, a model with a human-like lipoprotein metabolism. Methods: Obesity and dyslipidemia were induced with a 20-week free choice diet, which presents hamsters with a choice between control chow diet or high fat/cholesterol diet, and normal water or 10% fructose water. Obese hamsters were then kept on this free choice diet and treated subcutaneously once daily with vehicle, semaglutide 15 nmol/kg or survodutide 15 nmol/kg for 5 weeks. Results: Compared with vehicle, semaglutide and survodutide led to a 17% and 11% body weight reduction, respectively (both p<0.001 vs vehicle). Compared to vehicle, both chow diet and high fat diet intakes were significantly lower during the first week of semaglutide treatment, but then returned to baseline values. However, semaglutide significantly increased normal water intake and reduced fructose-enriched water intake during the whole treatment period (both p<0.001). Survodutide had a different effect, as it did not alter chow diet and normal water intakes, but significantly reduced high fat diet and fructose-enriched water intakes during the 5-week treatment period. Semaglutide and survodutide significantly reduced plasma insulin levels and the HOMA-IR index of insulin resistance (both p<0.01 vs. vehicle). Both semaglutide and survodutide significantly reduced plasma total cholesterol levels by 24% and 41%, respectively (both p<0.001). This hypocholesterolemic effect led to lower HDL-cholesterol levels (-25%, p<0.001) but unchanged LDL-cholesterol levels for hamsters treated with semaglutide. In contrast, in hamsters treated with survodutide, cholesterol lowering was observed in all lipoprotein fractions, including LDL-cholesterol (-39%, p<0.001). Conclusion: Semaglutide and survodutide both induce weight loss and lower HOMA-IR, but have different effects on food preference and dyslipidemia in the obese hamster model; such effects may be attributed to the GCGR agonism of survodutide. These preclinical data highlight the potential metabolic benefits of the GCGR/GLP-1R dual agonist survodutide for the treatment of obesity and related metabolic comorbidities.

Presentation: 6/3/2024
7004 Systems genetics analysis to identify candidate genes for fat distribution in BXD mice
Authors: Kim N , Ryu D , Oh C M
Published: October 2024

Disclosure: N. Kim: None. D. Ryu: None. C. Oh: None.

Obesity is defined as the accumulation of excess fat in the body. Although obesity is the main cause of metabolic disorders, not all obese people have metabolic disorders. Among many factors identified, the ratio of visceral (vWAT) to subcutaneous white adipose tissue (sWAT), representing body fat distribution, has been elucidated to be closely associated with metabolic health. Body fat distribution has been proposed as a possible explanation for this discrepancy. To investigate the regulation of body fat distribution, we performed a genetic analysis using the phenotype data and male subcutaneous fat microarray data from the BXD mouse genetic reference population. Our analysis identified H2-Ke6 (Hsd17b8), encoding hydroxysteroid 17-beta dehydrogenase, as a candidate target for adipose tissue plasticity. To further explore its role, we employed multiple approaches to reveal the effect of Hsd17b8 inhibition. First, lipid accumulation was attenuated in 3T3-L1 preadipocytes where Hsd17b8 was inhibited by CRISPER/Cas9 as well as lasalocid. Furthermore, we confirmed that the expression of adipogenesis-related transcription factor as well as mature adipocyte marker was decreased in terminally differentiated 3T3-L1. Specifically, CCAAT/enchancer binding protein α (Cebpa), peroxisome proliferator-activated receptor γ (Pparg), adiponectin (Adipoq), and fatty acid binding protein 4 (Fabp4) were transcriptionally downregulated. Consistently, in C. elegans, we used RNA interference (RNAi) to inhibit the expression of the Hsd17b8 ortholog, dhs-25, and observed a reduction in lipid accumulation. All these data suggest that the reduction in lipid accumulation in differentiated 3T3-L1 cells by the inhibition of Hsd17b8 is attributed to the suppression of early differentiation during the adipogenesis process. On top of that, to determine whether Hsd17b8 indeed influences body fat distribution in vitro, we utilized IngWAT Mouse Immortalized Preadipocyte Cell Line derived from subcutaneous white adipose tissue (sWAT) of a wild-type mouse. In contrast to the previous findings, we observed an increase in lipid accumulation of IngWAT when Hsd17b8 was inhibited. Surprisingly, the elevation of lipid accumulation in sWAT, as seen in gynoid obesity, has been revealed to be indicative of robust metabolic health compared to android obesity. Collectively, these data suggest that Hsd17b8 may represent a novel therapeutic target for the treatment of obesity. Our study provides valuable insights into the mechanisms underlying metabolic health in obesity and highlights the potential of Hsd17b8 as a therapeutic target for modulating adipose tissue plasticity.

Presentation: 6/3/2024
7097 The role of mitochondrial fraction locating cytoplasmic and peridroplet area in white adipocyte
Authors: Mori Ichiro , Ishizuka Tatsuo , Morita Hiroyuki , Kajita Kazuo
Published: October 2024

Disclosure: I. Mori: None. T. Ishizuka: None. H. Morita: None. K. Kajita: None.

White adipocytes (WAs) are involved in the formation of obesity and insulin resistance, but little is known about the role of WAs mitochondria. A recent study revealed that the mitochondria of brown adipocytes (BAs) consist of cytoplasmic mitochondria CM), which is responsible for β-oxidation, and peridroplet mitochondria (PDM), which supplies triglyceride to lipid droplets. However, it is unclear whether such a functional division exist in WA mitochondria. In this study, we examined whether the pellets obtained from cytoplasmic and oil layers of WAs of C57/BL/J mice by centrifugation were mitochondria. Since mitochondrial DNA, mitochondrial protein, Mitotracker Red staining, and mitochondrial images in electron microscope were detected in both fractions, they were considered to be cytoplasmic mitochondria (CMw) and peridroplet mitochondria (PDMw) in WAs, respectively. The amount of CMw and PDMw were greater in epididymal fat than in inguinal fat. CMw had higher β-oxidation activity than PDMw. PDMw was associated with perilipin 1/3 and diacylglycerol acyltransferase 2. The amount of PDMw was elevated in epididymal fat of mice fed a high-fat diet (HFD) for 2 and 4 weeks compared to normal chew-fed mice. These results suggested that CMw was involved in β-oxidation, and PDMw in droplet expansion. Although numerous researches have been shown that amount of mitochondria is suppressed in obese WAs, our results revealed that PDMw might be involved in the early stage of obesity formation.

Presentation: 6/1/2024
8328 Trends and Associated Factors of Obesity Among Patients with Diabetes Mellitus : Nationwide Survey in Thailand
Authors: Samakkarnthai Parinya , kookanok chutawat , Poochanasri Methavee , Kaewput Wisit , Rangsin Ram , Sathavarodom Nattapol , Boonyavarakul Apussanee
Published: October 2024

Disclosure: P. Samakkarnthai: None. C. kookanok: None. M. Poochanasri: None. W. Kaewput: None. R. Rangsin: None. N. Sathavarodom: None. A. Boonyavarakul: None.

Background: There are numerous health complications linked to obesity, especially in Diabetic Patients. However, the prevalence of obesity in people with diabetes is still unclear. Methodology: In 2014 and 2018, sequential cross-sectional investigations were carried out on patients receiving medical treatment at hospitals enrolled in Thailand's Universal Coverage Scheme. These hospitals are located throughout the country and provide care at various levels. Our study seeks to ascertain the trends and factors associated with obesity in individuals with diabetes in Thailand. Results: A total of 33,288 and 38,568 electronic medical records for individuals in 2014 and 2018, respectively, were included in the study. Obesity was 50.3% in 2014 and 50.7% in 2018. The mean BMI in 2014 was 25.5; in 2018, it increased to 25.7. The paired samples t-test indicated a statistically significant change between the two periods (95% CI: -0.20 to -0.05, p < 0.001). Obesity is associated with various factors, including receiving care in an urban standard/advanced hospital (OR 1.51, 95% CI: 1.13-2.01), an indoor occupation (OR 1.40, CI: 1.16-1.40), ex-smoker (OR 1.51, 95% CI: 1.06-2.13), gout (OR 1.20, 95% CI: 1.01-1.43) and hypertension (OR 1.40, 95% CI: 1.18-1.67)Conclusions: Our research highlights the rise in obesity rates and BMI changes among diabetic patients between 2014 and 2018. These findings reinforce the strong connection between obesity and various health issues. Notably, urban standard/advanced hospitals, indoor occupation, and ex-smokers tend to have higher obesity rates. The association between obesity and conditions like gout and hypertension underscores the need for effective weight management strategies incorporated with treating comorbidity in diabetic patients.

Presentation: 6/3/2024
7682 Triglyceride Tango: when Triglycerides take legs for a spin
Authors: Misra Daniel , Roger Brennan Michael , Misra Lynda , Kiryakoza Morgan
Published: October 2024

Disclosure: D. Misra: None. M.R. Brennan: None. L. Misra: None. M. Kiryakoza: None.

A 33-year-old male with no significant medical history presented with acute abdominal pain and n/v. The patient stated his RLQ pain extended down his R. leg resulting in weakness. He was on no medications at home. Vitals signs were stable, and the physical exam revealed diffuse abdominal tenderness in the RLQ and R. flank area with guarding, but no rebound and Neuro exam showed 4/5 strength in the RLE, the rest of the neuro exam was non-focal. Labs revealed an elevated lipase > than 3 times the upper limit and an elevation in transaminases. Other labs including blood glucose and white blood cell count were normal. CT was also performed and revealed significant inflammatory stranding of the pancreatic head and neck along the duodenum. The working diagnosis was pancreatitis. IV fluids were started, and the patient received IV Dilaudid for pain. There was no improvement in his symptoms overnight, so an abdominal CT was repeated. Imaging showed an interval development of a phlegmon and free fluid along the right paracolic gutter extending to the porta hepatis. The patient’s lipid panel revealed a triglyceride level of >1420 mg/dl. Endocrine was consulted and recommended initiation of a fenofibrate and atorvastatin. Although the patient was not a diabetic, endocrinology gave 20 units of basal insulin to the patient (Lantus). Within 24 hours of initiating basal insulin, the triglycerides fell to 680 mg/dl and the patient’s symptoms resolved. The patient was discharged home on day #3 on fenofibrate 160 mg/day and atorvastatin 40 mg/day. The patient was told to follow up with PCP for dyslipidemia and additional work up for transient right sided weakness. The two commonest causes of pancreatitis are alcohol and gallbladder disease, but it is important to entertain other causes. A lipid panel was drawn due to both pancreatitis and the right sided weakness, both of which resolved with the lowering of triglycerides. It is uncertain if hypertriglyceridemia is directly attributed to the right sided weakness, although neurologic findings due to hyperviscosity syndrome in hypertriglyceridemia have been described. If a causal relationship can be established, additional therapy such as anti-platelet therapy should be considered. This case also demonstrates that severe hypertriglyceridemia can be controlled with oral medications and subcutaneous insulin, even in non-diabetics, as opposed to IV insulin which could shorten hospital stays and decrease medical costs.

Presentation: 6/3/2024
8585 Using Stimulants to Treat Childhood Obesity
Authors: Elatrash Citrine , Sisley Stephanie
Published: October 2024

Disclosure: C. Elatrash: None. S.R. Sisley: None.

Background: Hyperphagia, characterized by excessive hunger, can significantly contribute to weight gain in early-onset childhood obesity and lacks an FDA-approved therapy. Stimulants commonly used in the treatment of attention deficit and hyperactivity disorder (ADHD) have a significant side effect of suppressing appetite. However, there is no data on the effectiveness of stimulants to reduce measures of obesity in children with severe obesity and hyperphagia. Methods: We retrospectively analyzed electronic medical records of children < 17 years old with severe, early-onset obesity (defined as a Body Mass Index (BMI) ≥ 120% of the 95th percentile (BMI%95th) prior to age 5 years) who were seen in the Genetic Disorders of Obesity Program (GDOP) at Texas Children’s Hospital (TCH). We included children who had a history of abnormal food behavior consistent with a clinical diagnosis of hyperphagia by having 2 of 9 symptoms of hyperphagia (consuming large portions, consistently feeling hungry, not feeling full with one serving, temper tantrums over food, asking for food frequently, sneaking food, getting up at night to eat, hiding food, constant asking for snacks) and were prescribed lisdexamfetamine treatment for hyperphagia for 6 months. We extracted BMI %95th for up to 12 months prior to treatment and 6 months after treatment. Paired t-tests were utilized to compare data from pre- vs. post-treatment. Results: Our cohort included 22 patients and was 68.2% female, 50% non-Hispanic White, 36.4% Hispanic white, and 13.6% black, with a mean age of 7.73 years±3.82 (range 3-17 years). There was a significant decrease in BMI%95th after treatment with lisdexamfetamine (167.3±38.8 vs. 158.0±40.2; p<0.001). We also observed a significant change in the rate of weight gain after lisdexamfetamine treatment; prior to treatment, patients gained 0.6 BMI%95th points/month compared to a loss of 1.9 points/month after treatment (p=0.002). 16 (72.72%) patients reported tolerable side effects, the rate of side effects was (33)33.33%. 19(57.57%) lasted from 1 week to 1 month and 6(18.18%) lasted more than 1 month. Side effects included adverse behavioral (9)27.27%, sleep disturbance (5)15.15%, and headache (4)12.12%. Conclusion: Children with severe obesity and clinical hyperphagia showed reductions in BMI%95th after six months of lisdexamfetamine treatment. Future research is needed to confirm the clinical efficacy of lisdexamfetamine in this high-risk population. Keywords: Childhood obesity, Stimulants, Hyperphagia, Pharmacologic Treatment

Presentation: 6/3/2024
7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma
Authors: Attah R C , Sirisena I
Published: October 2024

Disclosure: R.C. Attah: None. I. Sirisena: None.

Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref <30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref <1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg <205 pg/mL), normetanephrine 244.1 (ref <210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (>4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases.

Presentation: 6/1/2024
8267 A Case of Pineal Gland Cyst and Adrenal Adenoma- Is this a New Syndrome?
Authors: SIDDIQUI Mahrukh , Rafat Ummara , Shaik Shayann , Gilden Janice L
Published: October 2024

Disclosure: M. Siddiqui: None. U. Rafat: None. S. Shaik: None. J.L. Gilden: None.

Background: The Pineal Gland receives information through a complex multi-neuronal pathway and is responsible for the secretion of melatonin, a hormone regulated by circadian rhythm and suppressed by light stimuli. Melatonin is involved in biological rhythms and regulates immunomodulation, temperature homeostasis and maturation of hypothalamic-pituitary and gonadal axis, and can also modulate thyroid, prolactin, growth hormone, cortisol, and ACTH activity. Other effects include downregulation of thyroid activity. In addition, studies have shown that pineal body extracts can cause a minor increase in the zona glomerulosa and fasciculata of the adrenal gland. Case: A 54-year-old male with recurrent nephrolithiasis, obstructive sleep apnea and chronic rhinosinusitis, first presented to Endocrinology Clinic in 2018 for evaluation of an incidental adrenal adenoma (CT abdomen -2.8 cm, less than 10 Hounsfield units, left sided lipid rich adrenal adenoma). He had new onset erectile dysfunction, decreased libido, and fatigue. Initial lab work including LH, FSH, TSH, midnight salivary cortisol, ACTH, plasma cortisol AM, free and total testosterone, aldosterone, plasma and urine metanephrines/normetanephrines were all normal. MRI brain-1 cm thin-walled pineal cyst with internal characteristics compatible with proteinaceous benign pineal cyst. He was then lost to follow-up for 5 yrs due to the COVID pandemic. He had tried taking “testosterone protein builders”, but his symptoms remained. In addition, he now has twice weekly dull occipital headaches, relieved by ibuprofen. Lab tests-elevation in 1of 2 MN salivary cortisol samples at 0.58 mcg/dL (nl≤0.09), ACTH 12pg/mL(0-47), IGF1 261 ng/mL(50-317), and low total testosterone 222 ng/dl (250-1100) Free testosterone 36 pg/mL(35-155), borderline low TSH 0.386 µIU/ml(0.55-4.78), Free T3 and Free T4 were normal, thyroid antibodies-negative . Rest of the hormone evaluation was otherwise normal, LH 4.90 mIU/mL(1.5-9.3), FSH 11.10 mIU/mL (1.4-18.1), Prolactin 6.8 ng/mL(2.1-17.7). Thyroid Ultrasound-homogeneous echogenicity of the thyroid gland without discrete thyroid nodules. Repeat MRI brain- benign pineal cyst which was stable with no midline shift or mass effect. Repeat CT adrenal gland-lipid rich adrenal adenoma slightly reduced in size from 2.8 to 2.4 cm. Lab tests returned to normal one month later. Conclusion: Although it is unclear whether there is an exact association between this patient’s pineal cyst and adrenal adenoma, there have been intermittent hormonal abnormalities and symptoms consistent with hypogonadism and/or adrenal, also possibly related to the pineal abnormality. Although more research needs to be conducted explaining the relationship between the pineal and pituitary, and the adrenal gland, this clinical case suggests that there may be a relationship between these two abnormalities and symptoms.

Presentation: 6/2/2024
7658 A Case of Recurrent Cardiac Tamponade as Initial Presentation of Primary Adrenal Insufficiency
Authors: Farooq Aneeza , Ghumatkar Apeksha , Snitzer Jack
Published: October 2024

Disclosure: A. Farooq: None. A. Ghumatkar: None. J. Snitzer: None.

Introduction:Cardiac tamponade, a life-threatening emergency, can be associated with primary adrenal insufficiency (Addison Disease), and accurate diagnosis requires a high degree of clinical suspicion in patients with uncertain etiology and nonspecific signs and symptoms. Case Presentation:A 58-year-old female with a history of Hashimoto thyroiditis was evaluated in the hospital for two episodes of cardiac tamponade requiring emergent pericardiocentesis within one month. The patient had been experiencing symptoms of fatigue, nausea, lightheadedness, dizziness, hiccups, and tanned skin for the past year. She also had a recent flu-like illness with nausea and vomiting four months before her current presentation. Her vitals were notable for hypotension during these episodes. Her lab work showed hyponatremia (128 mEq/L, reference range: 136-145 mEq/L) with normal potassium and glucose levels. Her thyroid function tests were within normal limits on her home levothyroxine dosage (TSH 4.588 IU/ml, reference range: 0.5-8.9 IU/ml). An ACTH stimulation test was performed based on the patient's clinical presentation, consistent with adrenal insufficiency. Her baseline cortisol level was 5.9 mcg/dL (reference range: 6.7-22 mcg/dL), a post-ACTH stimulation level of 6.7 mcg/dL after 30 minutes, and 6.0 mcg/dL after 60 minutes. Her 21 alpha-hydroxylase antibody titer was also positive for Addison Disease (231U/mL, reference range <1 IU/mL). A CT scan of the abdomen with intravenous contrast was done, which revealed no abnormality of the adrenal glands. She was treated with stress doses of hydrocortisone during hospitalization and discharged with maintenance dosage and follow-up with endocrinology. She had another episode of acute adrenal crisis about a month later but had no pericardial effusion this time and responded well to the treatment with stress doses of steroids. She has remained healthy at 14 years of follow-up. Conclusion: This case emphasizes the need to consider adrenal insufficiency in the evaluation of cardiac tamponade or pericardial effusions, especially in patients with existing autoimmune glandular disorders. This patient may have autoimmune polyglandular syndrome type 2 (APS-2), which is a cluster of two or more endocrine glandular disorders primarily diagnosed in adulthood and predominant in females. The risk of adrenal crisis is more than twofold in Addison disease due to APS-2. Lastly, this case highlights that hiccups can be related to adrenal insufficiency, with pathophysiology possibly involving diaphragmatic irritation due to adrenal inflammation that resolves with treatment.

Presentation: 6/3/2024
7203 A case of undifferentiated shock found to be due to voriconazole-related primary adrenal insufficiency
Authors: Zhang Kaleena X , Bergwitz Clemens
Published: October 2024

Disclosure: K.X. Zhang: None. C. Bergwitz: None.

Primary adrenal insufficiency can be a rare effect observed with azole antifungal therapy, classically ketoconazole, via inhibition of cortisol and aldosterone synthesis. Whether primary AI can be observed with newer triazole drugs used for neutropenic prophylaxis and treating invasive fungal infections is far less understood. We describe a case of a 65-year-old man with medical history notable for COPD and gout, who was on voriconazole for Aspergillus pneumonia, and admitted to the medical ICU with confusion and undifferentiated shock. His potassium was 6.5 mmol/L, sodium 133 mmol/L, bicarbonate 18 mmol/L, and blood pressure 72/63 requiring pressor support. Voriconazole was withdrawn. He also had a fever to 101.7F that was attributed to a gout flare, and he received a course of high dose prednisone. His shock and electrolyte abnormalities quickly resolved, and he was discharged on isavuconazole. At the 1 week mark, he was found to have a morning cortisol 2.3 ug/dL, potassium 5.4 mmol/L, and sodium 134 mmol/L, along with fatigue, nausea, and hypotension, which prompted resumption of steroid and mineralocorticoid replacement. One month after completing his course of isavuconazole, morning cortisol normalized to 11.0 ug/dL and ACTH 22.3 pg/mL. We present a convincing clinical story supporting the etiology of this patient’s initial shock as primary adrenal insufficiency related to a voriconazole effect. This case illustrates how iatrogenic AI can be a missed diagnosis in the emergency room setting. Primary AI has classically been reported following ketoconazole therapy, but there are only 4 reports of primary AI involving the newer triazole posaconazole, and none for voriconazole or isavuconazole. Due to the rarity of this effect, AI due to voriconazole was not on the initial shock differential and timely endocrine labs to seal the diagnosis (morning cortisol, ACTH, and renin/aldosterone levels) were not obtained. If our patient had not received steroids serendipitously for gout, he may have been at risk for adrenal crisis. Whereas central AI is more common and induced by chronic use of systemic steroids, it is important to also think about AI caused by antifungal therapy with newer azoles.

Presentation: 6/3/2024
6657 A rare case of a composite pheochromocytoma and ganglioneuroma in a 47-year-old male
Authors: Ekladios Catherine , Jason Levine Matthew
Published: October 2024

Disclosure: C. Ekladios: None. M.J. Levine: None.

Introduction: Pheochromocytoma is a rare tumor that originates from adrenal chromaffin cells. It remains a diagnostic challenge due to its diverse clinical manifestations. We present a case of pheochromocytoma, shedding light on its atypical presentation and diagnostic complexity.Case reportA 47-year-old male was referred to our clinic with a recent diagnosis of pheochromocytoma. Patient started having symptoms approximately two months prior to referral to our office. He initially presented to the emergency department (ED) with generalized weakness for three days, accompanied by feelings of “rushing of blood to the head” and a “rush of blood in the arms” every time he laid down. Symptoms would last for a few seconds and resolve without intervention. Vitals signs and physical examination (PE) were within normal limits. He had basic laboratory studies including BMP and CBC without any abnormalities. He was discharged home with instructions to follow-up outpatient. He returned to the ED two days after with a chief complaint of left sided chest pain associated with palpitations, pain was non-persistent, lasting a few seconds. On presentation his blood pressure was 142/89 mmHg, Pulse: 66 bpm, Temperature: 98.4 °F, and oxygen Saturation 100%. On PE, he had clear bilateral air entry and regular heart rate with no murmurs noted, EKG demonstrated no ischemic changes. Chest Xray showed no evidence of cardiopulmonary disease. A CTA revealed no pulmonary embolism, pleural effusion, or pneumothorax. However, a large heterogeneous adrenal mass was partially visualized, measuring 8.3 cm anteroposteriorly concerning for adrenal cortical carcinoma. His labs were pertinent for Metanephrine level of 0.52 nmol/L (nl:0-0.49) and Normetanephrine of 4.22 nmol/L (nl:0-0.89). Aldosterone level is 16.2 ng/dL and Renin activity was 0.1ng/mL. An abdominal CT scan confirmed a left adrenal mass measuring approximately 9.2 x 8.8 cm transaxially and 9.9 cm craniocaudal. He was seen in our office after discharge, at that time he was still experiencing tingling in both lower extremities that sometimes would wake him up from sleep. His blood pressure at the office was 125/83 mm Hg. In preparation for the surgery, we started treatment with Prazosin, followed by addition of Metoprolol succinate. Further work-up included a dexamethasone suppression test that ruled out Cushing’s syndrome and a negative RET proto-oncogene, ruling out MEN 2. Patient underwent laparoscopic left adrenalectomy without complications. Pathology results interestingly showed a composite pheochromocytoma and ganglioneuroma constituting 5 % of the mass volume, Ki-67 proliferative index was less than 1% for the pheochromocytoma and overall findings were consistent with a benign tumor.ConclusionOur case report emphasizes the necessity of a high index of suspicion for diagnosing pheochromocytoma in the absence of the classic symptoms.

Presentation: 6/2/2024
6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma
Authors: Omran Fatema , Bromley Sarah , Ilahi Marium , Zena Mohsen , Al-Refaie Waddah , Delto Joan , Preet Singh Awinder
Published: October 2024

Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None.

Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (<0.02 miu/ml), low FSH (<0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and <5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or >7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management.

Presentation: 6/3/2024
7762 A Unique Case Of Sepsis-Driven Bilateral Adrenal Hemorrhages In A Patient With HIT
Authors: Siddiqui A , Shalit B , Nadeem H , Khan Z , Pinkhasova D
Published: October 2024

Disclosure: A. Siddiqui: None. B. Shalit: None. H. Nadeem: None. Z. Khan: None. D. Pinkhasova: None.

Introduction: Bilateral adrenal hemorrhages, commonly seen in the setting of sepsis as Waterhouse Friderichsen syndrome, is a rare life-threatening condition. This process is driven by the release of bacterial endotoxins leading to the activation of coagulation, fibrinolysis, and proinflammatory pathways. It is by a similar process that now non-septic hypercoagulable states, including heparin-induced thrombocytopenia (HIT), factor V Leiden and protein C resistance are also being recognized as etiologic for bilateral adrenal hemorrhaging. The following case demonstrates a combination of the two etiologies leading to adrenal insufficiency from bilateral adrenal hemorrhages. Clinical Case: A 48-year-old male presented to the emergency department with right upper quadrant pain, dyspnea, and a low-grade fever. Laboratory results indicated leukocytosis with a predominance of neutrophils. Initial computed tomography imaging revealed a 4 x 3.5 cm right lower lobe multi-loculated lung abscess and multiple right lower lobe segmental/subsegmental pulmonary emboli. The patient was started on a heparin drip and empiric antibiotics. Infectious disease was consulted to help determine the etiology of the lung abscess. Extensive workup including sputum, blood, fungal cultures, and acid-fast bacillus smear testing were negative. The patient improved on routine broad-spectrum antibiotics and was planned to be transitioned to a direct oral anticoagulant until serial imaging revealed incidental bilateral 4 cm adrenal hemorrhages. Endocrinology was emergently consulted; a random cortisol level was drawn and found to be low at 2.7 (3-17 µg/dL) with an elevated Adrenocorticotropic hormone (ACTH) level of 114 (6 - 50 pg/mL) indicative of primary adrenal insufficiency. The patient subsequently became hypotensive and was started on stress-dose steroids. Upon further investigation, the patient was found to be thrombocytopenic, and hematology was involved. Based on his 4T score of 5, concern was raised for HIT and argatroban was initiated. Moreover, the patient was eventually stabilized for discharge with close follow-ups with endocrinology, infectious disease, and hematology as an outpatient. Conclusion: There have been 17 reported cases of bilateral adrenal hemorrhaging in the setting of HIT uniformly presenting with complete hemodynamic collapse. This case serves as even more unique given the added component of sepsis. Both sepsis and HIT respectively have been well established to pose individual risk for developing bilateral adrenal hemorrhages. Hence, we hope to highlight the importance of exploring all potential causes of adrenal insufficiency in the setting of bilateral adrenal hemorrhaging and emphasize the harms of anchoring to a single etiology.

Presentation: 6/3/2024