bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT151 Assessments Of Body Composition In Women With Reactive Hypoglycemia
Authors: Adamska Agnieszka , Buczyńska Angelika , Łuka Katarzyna , Wiatr Aleksandra , Siewko Katarzyna , Duraj Ewa , Jacek Krętowski Adam , Popławska-Kita Anna
Published: October 2023

Disclosure: A. Adamska: None. A. Buczyńska: None. K. Łuka: None. A. Wiatr: None. K. Siewko: None. E. Duraj: None. A. Krętowski: None. A. Popławska-Kita: None.

Introduction: Reactive hypoglycemia is characterized by low blood glucose level in non-diabetic patients. It manifests as a syndrome of adrenergic and neuroglycopenic symptoms in the postprandial period, and their resolution occurs after consuming carbohydrates. Reactive hypoglycaemia can also be seen in patients with insulin resistance and hyperinsulinism. In patients with reactive hypoglycemia can be observed disturbances in body composition. The aim of this study was to asses of body composition in women with reactive hypoglycaemia vs control group. Subjects and Methods: We examined 103 women: 49 subjects with RH and 54 control women matched for age and BMI. Four hours oral glucose tolerance test (OGTT) with 75 grams of glucose with estimation of serum glucose and insulin was performed. Body composition was analysed by dual-energy X-ray absorptiometry (DXA). Results: We did not observe differences in fat mass, fat free mass, android fat mass and fat free mass, gynoid fat mass and fat free mass and visceral adipose tissue estimated with DXA method between studied groups (all p>0.05). However, we have found positive relationship between fat mass and serum glucose concentration at 3rd hour of OGTT (r=0.29, p= 0.03) in the group of reactive hypoglycaemia. In the control group be observe relationships between android fat-free mass and serum glucose concentration at 3rd hour of OGTT (r=-0.3, p=0.02) and gynoid fat-free mass and serum glucose concentration at 3rd hour of OGTT (r=-0.27, p=0.04). Conclusions: Women with reactive hypoglycaemia is not differ in body composition estimated with DXA methods. However RH is connected in different manner with glucose homeostasis and fat and lean mass in comparison to control group.

Presentation: Saturday, June 17, 2023
SAT163 Title: Adult-onset Hyperinsulinemic Hypoglycemia Due To An Activating Mutation In Glucokinase
Authors: Vaid Sonal , Ghosh Raisa , Elenius Henrik , Cochran Craig , Chang Richard , Nilubol Naris , Muniyappa Ranganath
Published: October 2023

Disclosure: S. Vaid: None. R. Ghosh: None. H. Elenius: None. C. Cochran: None. R. Chang: None. N. Nilubol: None. R. Muniyappa: None.

Introduction: Glucokinase (GK), the key β-cell glucose sensor, determines the threshold for glucose-stimulated insulin secretion. Activating mutations of GK are infrequent causes (prevalence of 1.2%) of congenital hyperinsulinemic hypoglycemia (HH). Adult-onset of severe hypoglycemia due to GK-HH is extremely rare. Clinical Case: A 26-year-old well-nourished female (BMI, 27 kg/m2) with a recent history of dizziness, tremulousness, fatigue, sweating, and hunger, associated with weight gain presented for further workup. Hypoglycemia was noted, and Whipple's triad was confirmed. She had no family history of endocrine disease or hypoglycemia. Supervised fasting promptly produced symptomatic hypoglycemia with hyperinsulinemia. Laboratory studies revealed a low glucose level at 44 mg/dL; a plasma insulin level at 93 μIU/mL (<3 μIU/ml); a C-peptide level at 8.1 ng/mL (<0.6 ng/mL); pro-insulin at 266 pmol/L (<5 pmol/L); and beta-hydroxybutyrate <2.7 mmol/L. IGF2/IGF-1 ratio was 3.1 (<10) and renal and liver function was normal. Interestingly, a mixed meal also provoked significant hypoglycemia within an hour of consumption of a meal. Urine for sulfonylurea screen was negative, and so were anti-insulin antibodies. Imaging of the pancreas with computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound revealed a 1.2x0.8cm nodule on the superior margin of the body of the pancreas. 68Ga-DOTATATE​​ PET/CT (targeting somatostatin receptors) showed mild uptake coinciding with the nodule on the CT scan. Arteriography with calcium stimulation and venous sampling (ASVS) was non-localizing. The patient subsequently underwent laparoscopic exploration with intraoperative ultrasound (IOUS) of the pancreas followed by the enucleation of the pancreatic nodule. Histopathology of the nodule revealed a normal pancreatic tissue with no evidence of a neuroendocrine tumor. Change to multiple small meals, addition of cornstarch to diet, continuous blood glucose monitoring (CGM), diazoxide (70 mg oral, three times a day), and monthly octreotide LAR (30 mg) has allowed the patient to avoid hypoglycemia. Genetic testing by analysis of the genes known to cause hypoglycemia revealed a heterozygous GCK variant [c.1367C>T (p.Ala456Val), which was predicted to be a pathological mutation. This mutation is known to increase affinity for glucose, which leads to exaggerated insulin secretion. Conclusion: Our study highlights that in adults with non-insulinoma pancreatogenous hypoglycemia, genetic causes of HH should be considered in the differential diagnosis.

Presentation: Saturday, June 17, 2023
SAT168 Cholecalciferol - Cause Of Hypoglycemia In Patients With Insulin Dependent Diabetes Mellitus
Authors: Kalinchenko Svetlana , Vorslov Leonid , Sviderskaya Tatiana , Timofeeva Svetlana , Samburskaya Olga
Published: October 2023

Disclosure: S. Kalinchenko: None. L. Vorslov: None. T. Sviderskaya: None. S. Timofeeva: None. O. Samburskaya: None.

Hypoglycemia is a dangerous complication in patients with diabetes mellitus receiving insulin drugs. We found a previously undescribed cause of hypoglycemia caused by prescription of cholecalciferol. Materials and Methods. Five patients (ages 6, 14, 28, 37, and 45 years) with medically subcompensated insulin-dependent diabetes mellitus (HbA1c > 7%) with vitamin D deficiency (25(OH)D < 30 ng/mL) were under observation. To compensate for vitamin D deficiency, cholecalciferol preparations were prescribed in individually selected doses (2,000 to 20,000 IU), considering age and weight. Findings. As a result of using cholecalciferol (without changing diet and physical activity level) all patients had episodes of hypoglycemia at different terms of treatment - from one to two weeks (younger patients 6 and 14 years old) to 6-8 months (patients of older age groups 28, 37 and 45), which were recorded by the continuous glucose monitoring system FreeStyle Libre: glucose level less than 3.0 mmol/L was accompanied by associated symptoms (tremor, tachycardia, cold clammy sweats, and intense hunger), which necessitated a reduction in the dose of insulin drugs. Interpretation. Vitamin D deficiency is a pandemic of modern society. Overweight, obesity, arterial hypertension, metabolic syndrome, and diabetes mellitus are the clinical manifestations of vitamin D deficiency. Vitamin D regulates the expression of over 5,000 genes, and compensating for its deficiency not only increases the number of insulin receptors, but also increases their sensitivity, leveling out insulin resistance and preventing its development. On achieving an adequate vitamin D level (25(OH)D not less than 65 ng/ml and parathormone levels closer to the lower limit of normal ranges of 16-25 ng/ml) against the background of reduced or completely discontinued insulin drugs, glycated hemoglobin in the blood was determined after three months and its values were within the reference values in all five patients (HbA1c not more than 5.6%). Conclusion. In patients with diabetes receiving insulin therapy, correction of vitamin D deficiency should be accompanied by daily glucose monitoring and under strict medical supervision, with dose adjustment of insulin drugs to prevent the development of hypoglycemia.

Presentation: Saturday, June 17, 2023
SAT171 An Unusual Presentation Of Insulinoma With Postprandial Hypoglycemia
Authors: Melendez-Rivera Juan Gabriel , Morgan Farah Hena , Aneja Amandeep
Published: October 2023

Disclosure: J.G. Melendez-Rivera: None. F.H. Morgan: None. A. Aneja: None.

Background:  Insulinomas are rare neuroendocrine tumors of the pancreas with an incidence of four cases per million individuals per year. The most common presentation of insulinoma is fasting hypoglycemia with associated neuroglycopenic symptoms. Postprandial hypoglycemia has been previously reported, usually in combination with fasting hypoglycemia. Exclusive postprandial hypoglycemia is estimated to occur in 6% of insulinomas. Clinical Case:  A 61-year-old woman presented with episodes of postprandial blurry vision, diaphoresis, nausea, and dizziness occurring for the last 18 months that have become more frequent. The patient reported blood glucose measurements in the 35 - 40 mg/dL range at the time of symptoms. Fasting blood glucose levels remained consistently in the 70 - 90 mg/dL range. These symptoms were originally sporadic but progressively became more common to the point that they were occurring daily after meals, and she gained 20 pounds due to increased food intake. BMI was 36.28. Her physical exam was unremarkable. Fasting labs revealed a glucose of 82mg/dl and C-peptide of 2.8ng/ml with normal cortisol. After a short trial of a reactive hypoglycemia diet, the patient had no improvement in symptoms, and was admitted for a 72-hour fast. She developed hypoglycemia with a glucose of 42mg/dl within four hours of starting her inpatient fast. At the time of hypoglycemia, insulin and C-peptide were inappropriately normal (insulin 15.9 mIU/mL and C-peptide 2.57 ng/mL) with an elevated proinsulin (42.3 pmol/L). An MRI abdomen with and without IV contrast showed a 16 mm hypervascular mass in the head of the pancreas. She subsequently underwent endoscopic ultrasonography with fine needle aspiration showing findings consistent with a well-differentiated pancreatic neuroendocrine tumor. Ga-68 DOTATATE PET CT revealed increased DOTATATE avidity in the pancreatic head mass compatible with neuroendocrine tumor but no evidence of metastatic disease. She underwent surgical resection of the tumor with resolution of symptoms. Conclusion: The absence of fasting hypoglycemia does not rule out pancreatic neuroendocrine tumors. While rare, exclusive postprandial hypoglycemia can be seen in these types of tumors, especially proinsulin-secreting tumors. This case illustrates the importance of considering insulinoma during the evaluation of postprandial hypoglycemia in the absence of fasting hypoglycemia and persistent hypoglycemia despite dietary modifications.  

Presentation: Saturday, June 17, 2023
SAT172 Unmasking A Pediatric Disease In Adult, A Belated Diagnosis
Authors: Syed Hasan , Au Pak-ho , Gardner Michael J
Published: October 2023

Disclosure: H. Syed: None. P. Au: None. M.J. Gardner: None.

Background: Glycogen storage diseases (GSD) are a rare group of diseases that change the way the body uses and stores glycogen. They are usually diagnosed in the pediatric population. Hypoglycemia can be a sign. Clinical Case: A 32 year old female presented with worsening and more frequent episodes of hypoglycemia. She had no history of diabetes and was not on any hypoglycemic agents. She had been having episodes of spontaneous hypoglycemia since childhood and would get symptomatic as well. No comprehensive workup had been done prior. The episodes were becoming more frequent. A blinded continuous glucose monitor was placed on the patient to monitor her glucose levels. Results indeed showed few episodes of hypoglycemia with glucose levels in the 40s. Interestingly, she also had postprandial hyperglycemia with glucose level above 180 following an episode of hypoglycemia. She underwent a 72 hour fast in the hospital and became hypoglycemic within 24 hours with a low blood glucose of 55, consistent with hypoglycemia, and she was also symptomatic as well. At the same time, her beta hydroxybutyrate increased to 3.91 mmol/L, consistent with ketosis. Her insulin level and C-peptide level at the time of hypoglycemia were 4.35 mcunit/mL and 0.239 nmol/L, respectively, and thus insulinoma was ruled out. She next underwent a mixed meal study during which her postprandial blood glucose increased to at least 198 indicating postprandial hyperglycemia. At the same time, patient's postprandial lactate also elevated to 4 mmol/L, consistent with lactic acidosis. Her symptoms of hypoglycemia resolved once her blood sugar (BG) improved. She met criteria for Whipple’s triad. She also had had an 8 am cortisol of 13.06 mcg/dL and had an appropriate response to the ACTH stimulation test with a 60 minute post cortisol above 20 mcg/dL, thus ruling out adrenal insufficiency as a cause of hypoglycemia. These findings of the 72 hour fast that resulted in hypoglycemia, followed by postprandial hyperglycemia with lactic acidosis are consistent with Glycogen Storage Disorder Type 0. Treatment involves intake of uncooked cornstarch with protein. Patient incorporated both uncooked cornstarch along with increasing amount of protein in her diet and started using a continuous glucose monitor with alarm to monitor her BGs. As a result her episodes of frequent hypoglycemia improved. Conclusion: This case illustrates a rare case of hypoglycemia in an adult that was not thoroughly investigated when she was in her childhood and adolescence. This case teaches the importance of being familiar with pediatric conditions since it is possible that pediatric conditions, especially if they are missed by providers and not appropriately diagnosed.

Presentation: Saturday, June 17, 2023
SAT174 Doege-Potter Syndrome In A Patient With Solitary Fibrous Tumor Of The Lung
Authors: Mon Nandar , Krishnasamy Sathya S
Published: October 2023

Disclosure: N. Mon: None. S.S. Krishnasamy: None.

Doege-Potter Syndrome is a non-islet cell tumor hypoglycemia (NICTH) due to a solitary fibrous tumor (SFT) with overexpression of Insulin-like growth factor 2 (IGF2). We report a case of refractory hypoglycemia in a patient with SFT of the lung. Case presentation: A 67-year-old homeless male with hypertension, chronic smoker presented with altered mental status after his blood glucose was found 34mg/dl by EMS. His confusion improved after D50W. He could not recall the event but he reported that he missed his dinner prior to the event. He denied taking any antidiabetic medications. He was diagnosed with left lung solitary fibrous tumor without metastases a week ago after he presented to ER with dyspnea, cough and wheezing. CT chest reported a 21x15.6x18.7 cm lesion with mass effect on the left hemidiaphragm, mediastinum shift to the right and occluded left lower lobe bronchi. Core needle biopsy of the mass revealed SFT with necrosis. He was discharged with Medrol dosepak 4mg daily for presumptive treatment of COPD exacerbation and a plan for elective surgery. While in the ER his BG improved to 136mg/dl after D50W. Few hours later BG dropped to 42mg/dl and D10W infusion was started. Physical exam was unremarkable except bilateral pedal edema. Work up showed BG 42mg/dl, Insulin 3.3 (2.6-24.9 uIU/mL), C peptide 0.39 (1.1-4.4ng/mL), Proinsulin 4.7 (<18.8pmol/L), beta-hydroxybutyrate <0.05 (0.02-0.27mmol/l), 8AM cortisol 10.7 (7.0-25.0 ug/dl), albumin 3.2mg/dl, HbA1c 5.8%, IGF1 53ng/mL (34-245ng/mL), IGF2 203ng/mL (267-616ng/mL) with a IGF2:IGF1 ratio of 3.8. In our patient, the IGF2:IGF1 ratio was not >10 since his IGF 2 was suppressed by the recent steroid use. The rest of the clinical and biochemical features strongly suggested NICTH. His preoperative evaluation showed new onset HFrEF with volume overload. He underwent staged percutaneous coronary interventions with stents placement. He was given hydrocortisone 50mg q6H then to q8H during hospitalization and discharged home with hydrocortisone 40mg TID. He underwent radical resection of lung tumor after optimization of his cardiac condition. He was on stress dose of steroid during surgery. Since he was on high dose steroid for > 3months, hydrocortisone dose was tapered slowly after the surgery. Final biopsy reported solitary fibrous tumor extending to parenchymal staple line. Tumor cells are positive for CD34 and STAT6, and negative for desmin, SMA, and SOX10. He recovered uneventfully and was discharged home with prednisone 5mg daily and follow up in endocrine clinic. Conclusion: NICTH is a rare paraneoplastic syndrome characterized by low levels of insulin, C-peptide, proinsulin, and beta-hydroxybutyrate. A ratio of IGF-2/IGF-1 more than 10 confirms NICTH; however, normal ratio cannot exclude the diagnosis and factors such as low IGFBP 3 or steroid therapy for other conditions need to be considered. Surgery is the mainstay of treatment.

Presentation: Saturday, June 17, 2023
OR06-04 Environmental Pollutants Perfluoroalkyl Acids Potently Stimulated Aldosterone Biosynthesis
Authors: Caroccia Brasilina , Seccia Teresa M , Pallafacchina Giorgia , Piazza Maria , Caputo Ilaria , Rizzuto Rosario , Rossi Gian Paolo
Published: October 2023

Disclosure: B. Caroccia: None. T.M. Seccia: None. G. Pallafacchina: None. M. Piazza: None. I. Caputo: None. R. Rizzuto: None. G. Rossi: None.

A large environmental contamination of drinking water by perfluoroalkyl substances (PFAS) markedly increased by 8-fold the plasma levels of pentadecafluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in a Northern Italy population with that shows a high prevalence of arterial hypertension and cardiovascular disease. As the link between PFAS and arterial hypertension is unknown, we investigated if they could enhance the biosynthesis of aldosterone, the main mineralocorticoid hormone that has pressor effects. We exposed human adrenocortical carcinoma HAC15 cells to 1 µM or 10 µM concentration of PFOA and PFOS, alone or in combination, for 24, 48 or 72 hours and we measured changes in cell viability, aldosterone synthase (CYP11B2) mRNA, cell and mitochondrial reactive oxygen species (ROS), and aldosterone production in the absence or presence of the superoxide scavenger tempol. Experiments were also performed in the presence of 10 or 100 nM Ang II. We found that PFAS increased CYP11B2 mRNA by 3-fold and aldosterone secretion and mitochondrial ROS production by 2-fold over controls (p < 0.01 for all). PFAS also enhanced the effects of the aldosterone secretagogue Ang II on CYP11B2 mRNA and aldosterone secretion: 10 nM or 100 nM Ang II increased CYP11B2 mRNA by 12- and 52-fold, respectively, compared to vehicle (p < 0.001). Moreover, 1 µM PFAS potentiated the effect of 10 nM or 100 nM Ang II on CYP11B2 gene expression by 30- and 80-fold, respectively (p < 0.001). As the ROS scavenger tempol, which decreased ROS, significantly blunted the CYP11B2 gene expression induced by either PFAS alone, or by concomitant exposure to Ang II and PFAS, the effect of PFAS likely occurs via increased ROS generation. These results indicate that at concentrations mimicking those found in human plasma of exposed individuals, PFAS exert a prooxidant effect and act as potent disruptors of human adrenocortical cell function, thus implicating them as causative factors of human arterial hypertension due to aldosteronism.

Presentation: Thursday, June 15, 2023
OR06-05 Differential Regulation Of Transcriptional State Switching Revealed By Endocrine Disruptor Chemicals
Authors: Day Christopher , Yasar Pelin , Rodriguez Joseph
Published: October 2023

Disclosure: C. Day: None. P. Yasar: None. J. Rodriguez: None.

Gene regulation is complex, involving the coordination of hundreds of proteins that function to control genome accessibility, mediate enhancer-promoter interactions, and initiate transcription. At individual loci, transcriptional initiation is stochastic in time, resulting in short periods of nascent RNA synthesis known as transcriptional bursts. Some genes switch between periods of transcriptional bursting and long periods of inactivity. These variable periods of inactivity can last days and lead to gene expression heterogeneity in cancer cells. Here we investigate how transcriptional bursting of estrogen regulated genes is modulated by low affinity estrogen receptor alpha (ERα) ligands, specifically endocrine disruptor chemicals (EDCs). Using live cell MS2-imaging of the estrogen responsive TFF1 gene, we observed that cells treated with genistein or Bisphenol A (BPA) exhibited burst initiation and duration kinetics which were indistinguishable from cells induced with Estradiol (E2). However, there was a 50% reduction in the number of active alleles in BPA treated cells. Our data suggest that BPA treated cells can activate TFF1 alleles that are in transcriptionally permissive states, while E2 and genistein can additionally switch alleles from a repressed state to a transcriptionally permissive state. To understand the contribution of the enhancer on state switching, we deleted the nearby enhancer and observed a similar number of active alleles between cells treated with E2 or BPA. Taken together, our work reveals that ERα and the TFF1 enhancer have roles in activation and state switching at a heterogeneously expressed gene. Our results also highlight different modes of regulation for endocrine disruptor chemicals at the same gene.

Presentation: Thursday, June 15, 2023
FRI396 Coexisting Secondary Selective Adrenal Insufficiency And Primary Hypothyroidism In A Patient Previously Treated With Pembrolizumab As Breast Cancer Therapy
Authors: Mayers Raisa Amelia
Published: October 2023

Disclosure: R.A. Mayers: None.

Background: The novel use of checkpoint inhibitors has increased the development of Immune-related endocrinopathies, being the thyroid and the adrenal axis among the most commonly affected, although co-existence of both pathologies is not commonly reported. Clinical case: A 77-year-old woman was seen in the office for management of her multiple endocrinopathies after receiving Pembrolizumab therapy for triple negative receptor breast cancer. Ten months ago, she was started on a weekly based therapy with Pembrolizumab. Thyroid function tests were monitored on a monthly basis and initially resulted as normal. Five months after initiation of her therapy, she started to complain of nausea, dizziness and confusion. At that time, she was taken to the emergency department by her husband and was found to be hypotensive and with signs of dehydration. Her initial laboratory work was remarkable for adrenocorticotropic hormone levels lower than 5 pg/mL and her total random cortisol level of 4.5 mcg/dl. At that time, she was started on prednisone therapy and later transitioned to hydrocortisone 20mg in the morning and 10 mg at night. During her emergency evaluation her thyroid function tests were unremarkable. Twenty days after her discharge from the hospital her thyroid stimulating hormone level was rechecked and resulted as 37.18 mIU/L . She was started on levothyroxine therapy with 50 mcg daily. Pembrolizumab therapy was stopped after 6 months of initiation. Most recent laboratory work shows persistently elevated levels of thyroid stimulating hormone 11.21 mlU/L, with normal levels of free thyroxine ( 1.4 ng/dl) and total triiodothyronine (125 ng/dl) and negative markers of autoimmunity ( thyroglobulin antibodies level less than 1 IU/ml and thyroid peroxidase antibodies levels of 1 IU/ml). Her adrenal axis remains suppressed with adrenocorticotropic hormone levels less than 5 pg/Ml and morning cortisol level less than 0.05 mcg/dl after a trial off the steroid replacement. Follicle stimulating hormone, luteinizing hormone, insulin grow factor 1 and prolactin levels were checked and were within normal limits. Magnetic resonance of her brain with and without contrast did not show lesions on pituitary gland. Conclusion: This is one of the few cases reported of the co-existence of secondary adrenal insufficiency and primary hypothyroidism after therapy with Pembrolizumab.

Presentation: Friday, June 16, 2023
SAT425 Effects Of Endocrine-disrupting Polychlorinated Biphenyls On Adolescent Microglial Cytokine Expression And Responses To Secondary Inflammatory Challenge
Authors: Kissinger Shawn L , Fitzgibbon Addison J , Mejia Rafael A , Bell Margaret R
Published: October 2023

Disclosure: S.L. Kissinger: None. A.J. Fitzgibbon: None. R.A. Mejia: None. M.R. Bell: None.

Polychlorinated biphenyls (PCBs) are a group of ubiquitous environmental endocrine-disrupting chemicals (EDCs), and exposure is associated with endocrine, neuronal, and immune dysfunction in various tissue types. Innate immune cells of the nervous system called microglia are critical in responding to infection and injury, and disruption of these functions is associated with neurodegenerative disease and mental health disorders. In addition, microglia are known to regulate developmental processes during neonatal and adolescent periods, in hormone-sensitive and age- and sex-differentiated ways. Work in our lab has shown that early life PCBs can affect microglia function in ways that depend on the age and sex of the individual rat in vivo. Ongoing work uses in vitro approaches to demonstrate direct effects on microglia. In primary culture, preliminary data suggest that acute PCB exposure causes neonatal microglia to become hyperresponsive to a secondary challenge; however, effects in adolescent microglia are unknown. To test the hypothesis that PCB exposure directly alters microglia activity in an age- and sex-specific manner, we determined the effects of PCBs on cytokine gene expression in acutely isolated microglia, with or without a secondary lipopolysaccharide (LPS) challenge. Adolescent Sprague-Dawley rats underwent transcardial saline perfusion, brains were removed and homogenized into a single cell suspension with collagenase and mechanical disruption, and debris was removed. Microglia, identified as CD11b+ cells, were collected by magnetic bead isolation and plated in enriched media for 24 hours prior to experimentation. Cells were exposed to one of three concentrations of PCB 153 (0.1 µM, 1 µM, 10 µM), DMSO vehicle, or DMEM/F12 media control for 18 hours, followed by a 4-hour LPS challenge (0.5 µg/mL) or PBS vehicle control. RNA was isolated and converted to cDNA for qPCR analysis of Tnf and Il1b gene expression, analyzed by two-way (exposure x challenge) ANOVAs within both male and female cells. Results indicate that 1.0 µM PCB 153 exposure caused an increase in expression of both cytokines, more so in females than males. Preliminary results (n = 3) indicate that the 10 µM dose may also blunt the later LPS response. These results confirm that microglia are directly sensitive to PCBs, however they illustrate that cells may show differential responses depending on the stage of development. Continued work will explore acute cell toxicity and confirm release of cytokines. Adolescent microglia dysfunction from PCB exposure may be a mechanism of adolescent-onset disorders, or increased risk of neurodegenerative conditions triggered by additional challenges later in life.

Presentation: Saturday, June 17, 2023
SAT426 Long-term Nanomolar Bisphenol A (BPA) Exposure of MCF7 Cells Induces DNA Methylation Changes
Authors: Dela Cruz Sam Ezrael L , Velarde Michael C , Bagamasbad Pia D
Published: October 2023

Disclosure: S.L. Dela Cruz: None. M.C. Velarde: None. P.D. Bagamasbad: None.

Breast cancer (BCa) has the highest worldwide prevalence and mortality rate among cancers. For ER-positive luminal BCa, hormone deprivation therapy using drugs that inhibit the estrogen signaling axis is commonly employed. However, activation of ER may persist due to the presence of endocrine disrupting chemicals (EDCs) that are structurally similar to endogenous estrogens. Bisphenol A (BPA) is a known EDC found in consumer products and has been associated with increased BCa risk in various animal models. Mechanistically, BPA weakly binds and activates ER resulting in transcriptional changes. In addition, studies show that BPA potentially reprograms the epigenome through changes in DNA methylation. While methylome studies on BPA-exposed cancer models have been conducted, to the best of our knowledge, this has not been done on luminal BCa cells chronically exposed to environmentally relevant doses of BPA. The use of a chronic, nanomolar-dose treatment paradigm is significant as it more accurately reflects non-occupational environmental exposure. In this study, we investigated the epigenetic effects of chronic (8 weeks) nanomolar doses (10 nM) of BPA on the ER-positive BCa cell line MCF7. We probed single gene-level DNA methylation through Bisulfite Sequencing PCR (BSP) and genome-wide methylation through Reduced Representation Bisulfite PCR (RRBS). In silico analysis of publicly available data identified potential differentially methylated regions (DMRs) upon chronic BPA treatment. BSP showed minimal changes in methylation levels of CpGs within the target DMRs, while gene expression analysis via RT-qPCR did not find significant changes in mRNA levels of genes encompassing the target regions. Methylome-wide profiling of chronically treated cells identified DMRs that fall under gene promoters (DMPs) and gene coding regions (DMGs). Pathway analysis of DMPs indicated an association with death receptor signaling, with an overall predicted effect in inhibiting apoptosis. Network analysis revealed genes encompassing DMPs that interact with the BCa markers ESR1/2, BRCA1, and PGR. Based on the pathway and network analyses, we selected 8 genes for gene expression analysis and found that the expression of all 8 genes are unchanged following chronic BPA treatment. Taken together, our results show that chronic BPA exposure of MCF7 can induce subtle changes in DNA methylation. Although initial validation did not reveal changes in gene expression associated with differential methylation, we speculate that the incremental DNA methylation changes could accumulate over time resulting in further ER signaling dysregulation, exacerbating the BCa phenotype.

Presentation: Saturday, June 17, 2023
SAT429 Progesterone Secretion And The Estrous Cycle In The Mouse Are Disrupted By Mitochondrial Fusion Promoter M1 Injection During Proestrus
Authors: Budi Yovita Permata , Hsu Meng-Chieh , Lin Yi-Chun , Lee Yue-Jia , Chiu Hsin-Yi , Chiu Chih-Hsien , Jiang Yi-Fan
Published: October 2023

Disclosure: Y.P. Budi: None. M. Hsu: None. Y. Lin: None. Y. Lee: None. H. Chiu: None. C. Chiu: None. Y. Jiang: None.

In the female reproductive system, mitochondria play a crucial role in steroid hormone synthesis. Literature reports on changes in mitochondrial dynamics throughout the ovarian cycle, but its role in the ovarian cycle is still unknown. In this study, a mitochondrial fusion promotor, M1, was used to study the impact of mitochondrial dynamics in the female reproductive system. The estrus cycle of mice was monitored before, during, and after the M1 treatment to test the impact of M1 on ovarian functions. Our results showed that M1 treatment in mice leads to the disruptions of estrous cycles in vagina smears. To observe the acute effects of M1, serum hormones level was observed, and the decrease in serum LH and progesterone was recorded in the animal. Similarly, our ovarian tissue culture also indicates inhibitions of progesterone secretion and ovulations. Although no significant changes in mitochondrial networks were observed in the ovaries, there was significant up-regulation of mitochondrial respiratory complexes in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the extracellular matrix molecules, remodeling enzymes, and adhesion signaling decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive system.

Presentation: Saturday, June 17, 2023
SAT430 Effect Of Organochlorine Pesticides On Brown Adipose Thermogenesis
Authors: Huang Shenq-Shyang , Jugan Juliann Amela , Harrigan Jenna , Singla Aman , Huang Victoria , Mann Chanapa Michelle , La Merrill Michele
Published: October 2023

Disclosure: S. Huang: None. J.A. Jugan: None. J. Harrigan: None. A. Singla: None. V. Huang: None. C.M. Mann: None. M. La Merrill: None.

Mammalian non-shivering thermogenesis is canonically controlled by β-adrenergic signaling in brown adipose tissue. The β-adrenergic receptors Adrb1, Adrb2, and Adrb3 receive the signals from upstream sympathetic neurons, activate adenylyl cyclase, and increase the expression of uncoupled protein-1 (UCP1) which dissipates energy to produce heat. The banned but persistent pesticide dichlorodiphenyltrichloroethane (DDT) along with its metabolite, dichlorodiphenyldichloroethylene (DDE), jointly referred to as DDX, are consistently associated with increased risk of present-day obesity and type II diabetes. In addition, DDX reduced body temperature by reducing sympathetic axons innervation in mice. However, the effect of DDX on the expression of β-adrenergic receptors and thermogenesis in brown adipocytes and other mammals is unclear. Therefore, the association between DDX exposure and the expression of β-adrenergic receptors and thermogenesis in vitro and in vivo was investigated. To this aim, Sprague-Dawley (SD) rats were fed high-fat diet and gavage of either a very low dose DDX mixture (5.6μg/kg weekly for 4 weeks) or olive oil vehicle control. DDX caused a significant reduction in body temperature after two weeks without significant changes in caloric intake or food efficiency. Notably, among all the β-adrenergic receptors, only Adrb3, and Ucp1 were downregulated in the brown adipose of DDX-treated rats. These results suggest that DDX reduces body temperature by attenuating Adrb3 expression in rat brown adipose tissue. To test whether this could explain the previously observed risk of human obesity associated with DDX exposure, we used immortalized human brown adipocytes to evaluate the effect of DDX on the RNA expression of β-adrenergic receptors, UCP1, and thermogenic function. As observed in rat brown adipose, DDT and DDE each reduced the expression of ADRB3 and UCP1, but not ADRB1 or ADRB2 in immortalized human brown adipocytes. Further, DDT and DDE each decreased heat produced by the human brown adipocytes. In addition, the reduced expression of UCP1 in DDX-treated human brown adipocytes was dependent on the presence of adenylyl cyclase (AC) activator, forskolin, demonstrating that the expression of UCP1 can be rescued by bypassing the upstream β3-adrenergic receptor. In conclusion, this evidence supports the hypothesis that obesogenic pesticides, DDT and DDE, attenuate thermogenesis by impairing brown adipocyte expression of the β3-adrenergic receptor and UCP1 in several mammalian species.

Presentation: Saturday, June 17, 2023
SAT437 Immunotherapy Induced Pituitary Apoplexy
Authors: Uddin Ashraf , Gardner Michael J , Akofu Anota , Sheung Nicole , Dejhansathit Siroj , Akabogu Nwamaka , Marium Fnu
Published: October 2023

Disclosure: A. Uddin: None. M.J. Gardner: None. A. Akofu: None. N. Sheung: None. S. Dejhansathit: None. N. Akabogu: None. F. Marium: None.

We present a case of a 42 year old male with past history of metastatic melanoma s/p 3 cycles of ipilimumab and nivolumab immunotherapy that originally was referred to endocrinology due to elevated prolactin of 40 and MRI finding of questionable 6 mm pituitary adenoma. There was not a clear other cause of prolactin elevation. Other notable labs in pituitary hormonal evaluation were elevated FSH of 24 and LH 16 with normal testosterone 663. TSH of 4.3 and FT4 of 1.22. After the 4th cycle of ipilimumab and nivolumab he had a severe headache that was unremitting, he called his oncology nurse line which instructed him to hydrate. He presented for admission to the hospital after coming confused, unsteady on his feet and his headache had already improved. Labs demonstrated severe hyponatremia at 111 with serum osm of 238 and urine osmolality of 504 and specific gravity of 1.012. Brain MRI demonstrated a 1.2 cm pituitary lesion compared to less than 1 month prior, consistent with hypophysitis. Repeat pituitary labs showed hypogonadotropic hypogonadism with total testosterone of 39 and inappropriately normal FSH of 7 and LH of 2, central hypothyroidism with TSH 0.232, FT4 0.70, FT3 1.8, secondary adrenal insufficiency with cosyntropin stimulation test up to cortisol of 16 for partial response and ACTH of 17. Hyponatremia was managed inpatient and he was discharged on appropriate hormone replacement. Subsequent brain MRI with normal pituitary finding without enhancing lesions. Repeat hormonal testing showed persistent hormonal deficiencies with undetectable cortisol and ACTH despite holding hydrocortisone therapies. Prolactin was also tested in the 4-10 range on repeat testing. He continued on nivolumab monotherapy with oncology.

This case report details a clear case of immunotherapy treatment leading to destruction of prolactinoma and presentation of pituitary apoplexy given the short time line of 1 month and cycle of therapy between radiographic and hormonal assessment. We hope this case helps bring awareness to the evolving list of conditions to survey for with immunotherapy and suggests a role of identifying prolactinomas biochemically and or radiographically to affect management. It may even suggest a role in treatment for medically refractory pituitary adenomas.

Presentation: Saturday, June 17, 2023
SAT640 Maternal Preconception Exposure Leads To The Propagation Of Disease
Authors: Davis Daniel Dewitt , Chamorro-Garcia Raquel , Diaz-Castillo Carlos
Published: October 2023

Disclosure: D.D. Davis: None. R. Chamorro-Garcia: None. C. Diaz-Castillo: None.

Tobacco products harbor a heterogeneous cluster of endocrine-disrupting chemicals (EDCs) that can lead to many adverse health effects, including obesity and other metabolic diseases. During critical developmental windows, exposure to EDCs found in tobacco products, including inorganic arsenic (iAs) and nicotine, can increase susceptibility to these diseases. An understudied window of significant influence on the susceptibility to developing adverse health effects in future generations is during maternal preconception (i.e., maternal preconception exposure, MPE). MPE involves essential processes of maternal germline development, such as oogenesis and folliculogenesis. Oogenesis begins at birth with an oogonium and goes through a maturation process that either ends after ovulation as a secondary oocyte or, if fertilized, becomes a zygote. Concurrently, folliculogenesis occurs and is the process by which the oocyte develops within the ovarian follicle into a mature egg. This ovarian follicle consists of many somatic cells that contribute to the maturation of the oocyte via paracrine mechanisms. We found that female offspring of mothers exposed to 200 µg/mL nicotine and male offspring exposed to both nicotine and a combination of 10 µg/L iAs + 200 µg/mL nicotine during MPE had higher weights during early development. Females whose mothers were exposed to 10 µg/L iAs showed an insulin resistance phenotype after intraperitoneal injection of insulin. Interestingly in males from mothers that were exposed to 10 µg/L iAs and 200 µg/mL nicotine we found impaired glucose tolerance after intraperitoneal injection of glucose. These data support the hypothesis that MPE is a critical window of susceptibility to metabolically associated diseases later in life. Future directions involve expanding the previously stated experiment by performing in vitro fertilization and embryonic implantation in mothers not exposed to our chemical treatment. The goal of this will be to investigate if the offsprings have similar health outcomes to the mice born of natural fertilization, which, if they do, would indicate the alterations were occurring before fertilization. We also aim to determine the mechanisms that trigger the phenotypes observed in the F1. We will analyze alterations of the somatic cells of the antral follicle and oocyte before ovulation by performing transcriptomic analyses.

Presentation: Saturday, June 17, 2023
THU009 Subclinical Cushing’s Syndrome In An ACTH-secreting Pituitary Macroadenoma
Authors: Akabogu Nwamaka Gloria , Kumar Deepak , Sheung Nicole , Akofu Anota , Uddin Ashraf , Dejhansathit Siroj , Marium Fnu , Goonetilleke Kurukulasuriya Lilamani Romayne
Published: October 2023

Disclosure: N.G. Akabogu: None. D. Kumar: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. S. Dejhansathit: None. F. Marium: None. L.G. Kurukulasuriya: None.

Background: Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). Case presentation: We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed 8AM cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of 8AM cortisol and ACTH on the high dose DST. 24hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Conclusion: Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome.

Presentation: Thursday, June 15, 2023
THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism
Authors: Mogar Nikita , McConnell Megan A , Yu Run , Weinreb Jane Eileen
Published: October 2023

Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None.

Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (<1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size >4 cm, internal calcifications, and HU >10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was <0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events.

Presentation: Thursday, June 15, 2023