bluuebunny/crossref_metadata_2025 huggingface dataset:
THU498 Establishing The Link Between Glucocorticoid Signaling And The Circadian Regulator DEC1 In Breast Cancer
Authors: Castro Mikaela I , Ybañez Weand S , Bagamasbad Pia D
Published: October 2023

Disclosure: M.I. Castro: None. W.S. Ybañez: None. P.D. Bagamasbad: None.

Epidemiological studies have linked altered circadian rhythms due to irregular shift work, chronic jet lag, and heightened night-time light exposure to increased breast cancer (BCa) pathogenesis. Dysregulated glucocorticoid (GC; CORT) signaling in BCa may further promote chronodisruption by directly regulating the cyclic expression of clock genes found in the breast. The differentiated embryo-chondrocyte expressed gene 1 (DEC1; also known as STRA13/SHARP2/ BHLHB2) is a transcription factor involved in the regulation of circadian rhythmicity and tumor progression of several cancer types including the breast and associated with hormone receptor signaling in BCa. In this study, we explored the involvement of DEC1 in the crosstalk between GC signaling and the circadian axis in BCa. To establish DEC1 expression pattern in BCa tumor samples, we assessed publicly available RNA-seq datasets from the Genotype-Tissue Expression Project and found no significant difference in DEC1 expression in tumors when compared to normal tissue controls. However, when tumor samples were stratified into molecular subtypes based on transcriptomic data from the Cancer Genome Atlas, DEC1 expression was significantly downregulated in triple-negative BCa (TNBC) in comparison to luminal subtypes. This pattern of expression was reflected in the BCa cell lines where we observed higher DEC1 expression in the estrogen receptor-positive MCF7 cells relative to nontumorigenic triple-negative MCF10A cells and the highly aggressive TNBC MDA-MB-231 cell line. To determine if DEC1 is regulated by GCs in the breast, we treated non-tumorigenic breast epithelial MCF10A cells and the TNBC MDA-MB-231 cells with increasing concentrations of CORT and observed that DEC1 mRNA expression decreases in response to increasing concentrations of CORT. Treatment of MCF10A and MDA-MB-231 cells with GC receptor (GR)- specific agonist RU486 abolished the GC-dependent repression of DEC1 expression and this pattern of DEC1 expression persisted even in the presence of the protein synthesis inhibitor cycloheximide, suggesting that DEC1 is a direct transcriptional target of GR in mammary epithelial cells. Through in silico analysis of publicly available ChIP-sequencing datasets from BCa cell lines, we identified multiple CORT-responsive cis-regulatory elements in the DEC1 locus that could mediate the CORT-dependent repression of DEC1 expression. Lentiviral knockdown of DEC1 in three breast epithelial cell lines was generated and will be used in cancer hallmark assays on proliferation, apoptosis, survival, and migration to assess the functional role of DEC1 in BCa. Taken together, our data will contribute to understanding the combined effect of GC signaling and circadian gene regulation towards BCa progression.

Presentation: Thursday, June 15, 2023
THU515 Vitamin D Binding Protein Induces Skeletal Muscle Atrophy And Contributes To Cancer-associated Muscle Wasting
Authors: Raiteri Tommaso , Reano Simone , Scircoli Andrea , Zaggia Ivan , Prodam Flavia , Filigheddu Nicoletta
Published: October 2023

Disclosure: T. Raiteri: None. S. Reano: None. A. Scircoli: None. I. Zaggia: None. F. Prodam: None. N. Filigheddu: None.

Vitamin D binding protein (VDBP), encoded by the Gc gene, is a multifunctional serum glycoprotein synthesized by hepatocytes, whose primary function is the transport of vitamin D metabolites in the bloodstream. In addition, VDBP enhances the chemotactic activity of neutrophil chemoattractants and takes part in the actin-scavenger system by acting as a monomeric G-actin-binding protein. Several studies have reported a correlation between increased levels of VDBP and various pathologies often associated with muscle wasting, including different types of tumors. Given these findings, we hypothesized that VDBP may play a role in muscle atrophy and cancer-associated muscle wasting and investigated its direct effects on skeletal muscle homeostasis in vitro and in vivo. We showed that, in C2C12 myotubes, VDBP uptake through megalin-mediated endocytosis induced mitochondrial dysfunction and exacerbation of mitophagy that resulted in atrophy. Furthermore, VDBP treatment impaired myoblast differentiation and the formation and stability of acetylcholine receptor (AChR) clusters, an in vitro model of neuromuscular junctions (NMJ). The main molecular mechanism behind the atrophic effect of VDBP is the perturbation of intracellular actin dynamics due to VDBP's ability to bind G-actin. To assess if VDBP has a causative role in muscle homeostasis also in vivo, we experimentally induced the expression of VDBP in Gc knock-out mice (VDBP KO) by adeno-associated virus (AAV)-mediated gene delivery, and we observed that a relatively small amount of circulating VDBP was sufficient to affect muscle performances and reduce muscle mass. Moreover, coherently with the in vitro data, VDBP induced morphological abnormalities in the NMJ. Coherently with the upregulation of VDBP observed in cancer patients, we detected an increase of VDBP in two commonly used models of cancer cachexia, C26 colon carcinoma and Lewis Lung Carcinoma (LLC) tumor-bearing mice. To test the hypothesis that VDBP could play a role in cancer-associated muscle wasting, we induced cancer cachexia in VDBP KO mice by inoculating LLC cells. Tumor-bearing VDBP KO mice preserved their body weight and performances, and the muscle loss and NMJ dismantling were minimal compared to cachectic WT mice. Although the primary function of VDBP is the transport of vitamin D metabolites, we demonstrated that VDBP acts as a hormone per se, having a direct pro-atrophic activity on skeletal muscle. Altogether, our data suggest that VDBP is a new player in the onset of cancer-associated muscle wasting, thus representing a potential therapeutic target to treat cancer cachexia.

Presentation: Thursday, June 15, 2023
THU525 Atypical Presentation Of Parathyroid Carcinoma In The Lungs
Authors: Nicolas Jacinto Jorg Jurgen , Reyes Oscar Paulo , Cating-Cabral Monica , Santiago Rex Michael , Andal Jose Jasper
Published: October 2023

Disclosure: J.N. Jacinto: None. O. Reyes: None. M. Cating-Cabral: None. R. Santiago: None. J. Andal: None.

A 66-year-old female with a history of parathyroid adenoma underwent partial parathyroidectomy and thyroidectomy of the right lobe in 2006. She has the following comorbidities: pre-diabetes, hypertension, multiple liver cysts, medullary nephrocalcinosis and nephrolithiasis, ureterolithiasis and uterine intramural myoma. She also has a strong familial disposition of endocrine tumors. During the last quarter of 2018, parathyroid hormone and calcium levels were elevated and parathyroid imaging revealed an adenoma on the posteromedial aspect of the left thyroid lobe. Removal of the adenoma was offered but insisted on medical treatment. In 2022, she was admitted for subarachnoid hemorrhage due to fall. There was an incidental finding of a lung mass with minimal pleural effusion on the right lung lobe. PET-scan revealed five FDG-avid nodules (SUV up to 9.6) with the largest in the right middle lobe measuring 2 x 2 x 2 cm. Percutaneous needle biopsy was performed which showed a tumor with fairly uniform cells in organoid nests and solid clusters. By immunohistochemistry (IHC), the tumor cells were diffusely and strongly positive for CK and GATA-3; focally positive for chromogranin and synaptophysin; and negative for TTF-1, Pax-8, and S100. This was signed out as an epithelial tumor with neuroendocrine features; the differential diagnosis includes pulmonary neuroendocrine tumor versus metastasis from the prior parathyroid lesion. She subsequently underwent completion thyroidectomy and video-assisted thoracoscopic surgery. The lung wedge resections both showed tumors with similar morphology and IHC staining pattern as the biopsy. Additional stains were also performed to rule out other entities, which were all negative (CK7, CK20, CD56, mammaglobin, GCDFP-15, TTF-1, S100, ER, Pax-8, HSA, and SALL-4). The Ki-67 proliferation index was 17.26%. Because the overall findings were not definitive, comprehensive genomic profiling by next generation sequencing (NGS) was recommended and subsequently performed. NGS showed gene alteration in CDC73, with a variant allele frequency of 50%; this finding has been documented in parathyroid carcinoma. Pre-operative parathyroid hormone levels remained unchanged (408 to 397 pg/ml) despite surgery. Currently, there is no available targeted therapy to address her genomic alteration. Hyperparathyroidism-jaw tumor syndrome was entertained. The multidisciplinary team advised en-bloc resection of the lung tumor and additional gene testing for family members. She opted for palliative care and is on cinacalcet for her hyperparathyroidism.

Presentation: Thursday, June 15, 2023
THU530 What Works For Ferret, Works For Man
Authors: Bhatt Plukshi J , Bendaram Snigdha Reddy , Kantorovich Vitaly
Published: October 2023

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

Insulinomas are rare pancreatic neuroendocrine tumors with an incidence of 4 cases per million per year and present with hypoglycemic symptoms due to uncontrolled and excessive insulin secretion by the tumor. Although most commonly benign and treated with surgery, 5-10% are malignant, inoperable and are managed medically with somatostatin analogs, chemotherapy, mTOR inhibitors and diazoxide. A 28 year old male with a history of metastatic insulinoma with progressive disease and refractory hypoglycemia presented with lethargy, diaphoresis, and blood glucose (BG) level of 32mg/dL [65-99].  He was previously admitted for severe hypoglycemia and was treated with FOLFOX, LUTATHERA, Octreotide, TPN, steroids and diazoxide suspension. Sugars were monitored via continuous glucose monitor (CGM) and insulin and C-peptide levels were closely monitored outpatient. Treatment was effective and medications were tapered off so that he no longer needed a CGM and was only on FOLFOX and octreotide prior to presentation. On admission, insulin level was 172 uIU/mL [<17], peaking at 312 uIU/mL and BG dropping to 22mg/dL. He was placed on a dextrose 10% infusion, TPN, diazoxide suspension, and CGM. This admission, however, his insulin levels were much higher requiring higher doses of diazoxide, but he was unable to tolerate the diazoxide solution due to extreme nausea and projectile vomiting, resigning him to a long-term stay in the ICU. Due to a lack of availability of other oral formulations in the US, compounding pharmacies were contacted and pharmaceutical grade diazoxide powder was compounded into 100mg capsules by an outside pharmacy. Dose was adjusted while monitoring BG and insulin levels. Prior to discharge, insulin level was 77.7 uIU/mL and BG levels had normalized. He was sent home on diazoxide 200mg twice a day, TPN, and CGM. FOLFOX was resumed. Outpatient follow up revealed euglycemia and suppressed insulin level of 12.3 uIU/mL [<17], allowing for further tapering of diazoxide dose and discontinuation of TPN. Diazoxide is known to be a safe and effective treatment for hypoglycemia in humans and ferrets alike. It inhibits insulin secretion in pancreatic B cells and increases hepatic glucose production. Side effects of nausea and vomiting can be a barrier to compliance, as seen in our patient. Currently, only oral solutions of diazoxide have been approved for human consumption whereas ferrets, commonly afflicted with insulinomas, are treated with oral pills. Changing the oral formulation to pill form allowed for better compliance, easy dose adjustments using insulin as a marker for response, and symptom resolution due to adequate suppression of insulin levels. Most importantly, it allowed for our patient to transfer out of the ICU and be discharged home with improved quality of life, a feat that was impossible without this change in formulation.

Presentation: Thursday, June 15, 2023
THU541 Impact Of Gender On Treatment Decisions And Outcome In Patients With Neuroendocrine Neoplasms
Authors: Beck Julia , Siebenhüner Alexander , Wild Damian , Christ Emanuel R , Refardt Julie
Published: October 2023

Disclosure: J. Beck: None. A. Siebenhüner: None. D. Wild: None. E.R. Christ: None. J. Refardt: None.

Introduction/Background: Gender differences affect the treatment of several diseases in both male and female patients. However, the influence of gender on treatment decisions and outcome in neuroendocrine neoplasms (NENs) has scarcely been investigated. Aims: Comparison of tumor characteristics, treatment decisions and outcome of patients with NENs, stratified by gender. Material and Methods: Retrospective analysis of the SwissNET cohort involving NENs of gastroenteropancreatic, pulmonal or unknown origin from 07/14 – 09/21. Site of origin, tumor grading, time to first treatment, choice of treatment and overall survival was assessed. Results: 2329 patients were included in the analysis with 54% being male and 46% female patients. No significant difference in site of origin, tumor grading and staging was found between male and female patients. There was also no difference in time of symptoms onset until diagnosis and first treatment intervention. Surgery was performed in 66.3% of male and 71% of the female patients, p=0.016. Meanwhile, male patients received more often PRRT (22% vs 19.3%, p=0.007) and chemotherapy (15.9% vs 12.7%, p=0.032). Despite the similar tumor characteristics, the median overall survival of male patients was significantly lower compared to female patients (Male: 124.8 months, Female: 158.5 months, p<0.001). Interestingly, this difference was most pronounced in patients with lung NENs (Male: 142 months, Female: not reached) and cancer of unknown origin (Male: 18.5 months, Female: 35 months). Conclusions: Male gender seems to be a risk factor for worse outcome, specifically for lung NENs and NENs of unknown origin. The underlying mechanisms of these findings remain to be established.

Presentation: Thursday, June 15, 2023
OR16-02 Histone ADP-Ribosylation Site Mutations As Oncogenic Drivers In Breast And Ovarian Cancers
Authors: Huang Dan , Camacho Cristel V , Nagari Anusha , Lee Kraus W
Published: October 2023

Disclosure: D. Huang: None. C.V. Camacho: None. A. Nagari: None. W.L. Kraus: Other; Self; - Founder and stockholder for Ribon Therapeutics, Inc. - Founder, stockholder, scientific advisory board member, member of the board of directors for ARase Therapeutics, Inc. - Coholder of U.S. Patent.

Recent studies have identified oncohistones, which are encoded by histone genes that harbor missense mutations, as a new class of cancer drivers. We found that many of the oncohistone mutations identified with the highest frequencies in human cancers occur on glutamate (Glu, E) and aspartate (Asp, D) residues, which are potential sites of ADP-ribosylation (ADPRylation). ADPRylation is a post-translational modification, which is catalyzed by the PARP family of ADP-ribosyl transferases and results in the covalent attachment of ADP-ribose on protein substrates. Unlike other well characterized histone modifications, the functions of histone ADPRylation are poorly characterized. Mass spectrometry analyses confirmed that 20 Glu or Asp residues subjected to oncohistone mutation are bona fide sites of ADPRylation by PARP-1. Ectopic expression of each of six different oncohistone mutants from three different core histones (H2B, H3, and H4) altered the proliferation of at least 2 out of 3 cancer cell lines, including MCF-7 and MDA-MB-231 breast cancer cells, as well as OVCAR-3 ovarian cancer cells. We focused on H2B-D51, whose mutation resulted in enhanced cell proliferation in both of the breast cancer cell lines for further characterization of its potential transcription regulatory effects. Proteomic (histone PTMs) and genomic (ATAC-Seq, ChIP-Seq and RNA-Seq) analyses revealed that loss of ADPRylation on H2B-D51 by mutation to alanine (Ala, A) or asparagine (Asn, N) dramatically enhanced p300-mediated acetylation of H2B, altered chromatin accessibility, and changed the pattern of gene expression in MDA-MB-231 cells. To determine the effects of H2B-D51 ADPRylation on cancer cell growth in vivo and their responses to the FDA-approved PARP inhibitor Niraparib, we performed xenograft tumor growth assays in immunocompromised mice using MDA-MB-231 cells ectopically expressing wild-type or D51A mutant histone H2B. Ectopic expression of the H2B-D51A mutant led to a significant increase in tumor growth versus wild-type H2B. Interestingly, these effects were inhibited by treatment with Niraparib, suggesting that the H2B-D51A mutant alone does not confer resistance to PARP inhibitor. Taken together, this study demonstrates that functional sites of Glu/Asp ADPRylation on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of ADPRylation. (This work was supported by grants from the NIH/NIDDK and CPRIT, and funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment to W.L.K.)

Presentation: Friday, June 16, 2023
SAT059 Metastatic Insulinoma Diagnosed Postpartum
Authors: Faber Alexis , Lam Han , Simon Rebecca
Published: October 2023

Disclosure: A. Faber: None. H. Lam: None. R. Simon: None.

Introduction: Insulinomas are rare neuroendocrine tumors derived from the beta cells of the pancreas. These tumors generally occur at a rate of four cases per million per year, and they are seen across all demographics. Affected patients present with symptoms of hypoglycemia, including confusion, diaphoresis, and palpitations. Insulinomas occur as single or multiple tumors, and can be benign or malignant. Insulinomas with metastases are defined as malignant. The primary treatment is surgical resection. However, in the case of metastatic insulinomas prognosis can be quite poor with limited treatment options. Case Presentation: A 24-year-old female employed as a nurse with otherwise negative medical history originally presented around 3 months postpartum with epigastric pain which was attributed to gas. Symptoms progressed to include lightheadedness, palpitations, and sweating. She checked her blood glucose during these events and noted it to be consistently in the 30s-40s. She would treat these episodes with food and had short-term improvement in symptoms. She presented to an outside hospital where imaging revealed: hepatomegaly with innumerable hypodense liver lesions, hypo-enhancing pancreatic head lesion, sclerotic focus in T4 vertebral body, as well as multiple enlarged upper abdominal lymph nodes including peripancreatic, porta hepatis, and gastrohepatic. Liver biopsy revealed well-differentiated neuroendocrine tumor, WHO grade 3 likely from a pancreatic primary and chemotherapy was initiated with carboplatin and paclitaxel with some response. However, hypoglycemia became refractory to management with 5% dextrose drip, so she was transferred to our facility for escalation of care. TPN was initiated and dextrose drip was escalated eventually to 40% dextrose. She was also given octreotide, hydrocortisone, and eventually diazoxide. Given degree of tumor burden as well as abdominal ascites and clinical condition, surgery was deemed high risk and not recommended. Tumor board meeting was held and her chemotherapy regimen was changed to Carboplatin/Etoposide/Atezolizumab. She subsequently underwent hepatic artery embolization twice with improvement of hypoglycemia. Despite decreasing dextrose drip requirements by over 50%, patient was unable to be liberated from dextrose infusion and had multiple discussions about management options and prognosis. The patient eventually elected to go home with home hospice. Discussion: Insulinoma diagnosed in pregnancy or shortly after pregnancy is extremely rare. There are only three case reports of malignant insulinoma diagnosed in or after pregnancy. Given the degree of extensive metastases at time of presentation, we expect our patient’s insulinoma was present prior to delivery. Hypoglycemia may have only manifested in the postpartum period when there was decreased levels of placenta-derived counterregulatory hormones.

Presentation: Saturday, June 17, 2023
SAT635 Role Of The Human Prolactin Receptor I-tail In The Pathogenesis Of Breast Cancer
Authors: Clevenger Charles V , Shen Shanwei
Published: October 2023

Disclosure: C.V. Clevenger: None. S. Shen: None.

Evidence from epidemiological, cellular, and genetic analyses indicate that the hormone prolactin (PRL) and its receptor (hPRLr) in humans are significantly involved in breast cancer pathogenesis. The intermediate form of hPRLr (hPRLrI) induces significant increases in proliferation and anchorage-independent growth of normal mammary epithelia in vitro when co-expressed with the long form hPRLr (hPRLrL). However, the exact mechanism of how the hPRLrI transforms mammary epithelium is not well understood. The hPRLrI is produced by alternative splicing that induces a frameshift, resulting in a premature stop codon and a novel 13 amino acid tail ("I-Tail") gain. The ubiquitin-like protein neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) was found to be associated with the I-tail by yeast two-hybrid analysis. Treatment with a selective NEDD8 inhibitor resulted in the altered stability of the hPRLrL and the death of breast cancer cells. Given this, we hypothesized that the hPRLrI I-tail contributes to mammary transformation. hPRLrL, hPRLrI, hPRLrIΔ13 (I-tail removed mutant due to loss of 13 C-terminal amino acid resides) were delivered to MCF10AT cells by lentivirus transduction and subsequently analyzed. Anchorage-independent cell growth was determined by soft agar assay, cell proliferation was determined with a Incucyte analysis, and cell motility was examined by wound healing assay. In addition, signaling pathway and differential gene expression alterations mediated by the I-tail were determined by RNA-seq and signaling analysis. Successful expression of the hPRLrL+hPRLrIΔ13 in the MCF10AT transfectant resulted in significant reductions or alterations of anchorage-independent growth, cell proliferation, ERK1/2 activation, and PRL-induced different gene expression. These findings demonstrate that the hPRLrI I-tail contributes to the transformation of normal mammary epithelia cells.

Presentation: Saturday, June 17, 2023
FRI235 Primary Adrenal Insufficiency As Presenting Symptom Of Disseminated Histoplasmosis And Cryptococcus Co-Infection In Immunocompetent Patient
Authors: Thompson Alicia
Published: October 2023

Disclosure: A. Thompson: None.

Background: Autoimmune adrenalitis remains the most common cause of primary adrenal insufficiency in the United States. Infectious etiologies from fungal sources are much less commonly seen. Below we discuss a case of disseminated histoplasmosis and cryptococcus that initially presented with primary adrenal insufficiency. Case: A 74 y/o F with history of Type 2 DM presented to the hospital with 3 months of fatigue and weight loss. She was initially found to be in DKA and shock requiring vasopressor support. Following the resolution of DKA, she remained hypotensive without obvious cause. A random cortisol was found to be 8.2 [6-25 ug/dL]. She then underwent an ACTH stimulation test and her cortisol level at 30 minutes was 5.9 ug/dL and at 60 minutes was 4.2 ug/dL. An ACTH level was obtained and found to be elevated at 69 [7.2-63 pg/mL]. She was subsequently started on Hydrocortisone and her shock resolved. CT adrenal glands were notable for bilateral adrenal masses measuring 4.5 cm on the right and 4.6 cm on the left with HU of 27. No other suspicious lesions were noted on imaging. An infectious work up was initiated, which was notable for fungal serologies positive of Histoplasmosis with titer of 1:8 (<1:8). Histoplasmosis urine antigen was positive as well. She was tested for Cryptococcus, which was positive with a titer of 1:8 (<1:8). She started treatment with Amphotericin B for 4 weeks followed by Itraconazole for maintenance therapy. Discussion: Primary adrenal insufficiency from invasive fungal infection remains uncommon and is found in less than 10% of cases. Disseminated fungal infections are identified as causes like histoplasmosis and paracoccidiomycosis. Disseminated cryptococcus is an exceedingly rare cause of adrenal insufficiency. These invasive infections can lead to bilateral enlargement of the adrenal glands and calcifications are seen on radiographic imaging. Such cases can also lead to perivasculitis and cause thrombosis and subsequent infarction of the adrenal glands. Disseminated fungal infections are more commonly seen in patients with underlying immunodeficiency such as HIV or those receiving immunosuppressant therapy. This case highlights that these infections can still be seen in those without a compromised immune system. Diagnosis can be challenging given the vague symptoms of adrenal insufficiency but should be considered in patients with electrolyte disturbances, hypoglycemia, and hypotension. There is potential for adrenal recovery following treatment with antifungal therapy. Conclusion: Although autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in the US, this case highlights the importance of evaluating for other potential causes such as infectious sources, which can be treated and potentially have adrenal recovery.

Presentation: Friday, June 16, 2023
FRI238 A Rare Combination Of Thyroiditis And Secondary Adrenal Insufficiency Likely Secondary To Hypophysitis In A Patient Treated With Immune Checkpoint Inhibitors
Authors: Patel Shivani , Aluko Oluwatomisin A , Thwe Ei Ei , Gallagher Thomas , Deshmukh Mrunalini
Published: October 2023

Disclosure: S. Patel: None. O.A. Aluko: None. E. Thwe: None. T. Gallagher: None. M. Deshmukh: None.

Introduction: Immune checkpoint inhibitors have shown significant improvement in treatment of various cancers. Thyroiditis and hypophysitis are well-known reported adverse effects of immune checkpoint inhibitors. However, the co-existence of thyroiditis and hypophysitis in patients treated with immune checkpoint inhibitors is rare. We hereby report a case of a patient with thyroiditis and secondary adrenal insufficiency secondary likely to hypophysitis who was treated with atezolizumab for hepatocellular carcinoma. Case Report: A 65 year old male with past medical history of type 2 diabetes mellitus, hepatocellular carcinoma status post transcatheter arterial chemoembolization on atezolizumab and bevacizumab, thyrotoxicosis, liver cirrhosis secondary to prior alcohol use presented to the ED for evaluation of intermittent dizziness. Vitals signs showed Temperature 97.7°F, BP 137/64 mmHg, HR 82 beats/min, RR 18 breaths/min, SpO2 98%. During the hospital course, work up revealed AM cortisol level of 0.7 μg/dL (N 4.2-22.4 μg/dL), ACTH 33 pg/dL (N 7.2-63.3 pg/dL), TSH <0.007 uIU/mL (N 0.45-4.5 uIU/mL), free t4 3.57 ng/dL (N 0.76-1.46 ng/dL), free t3 6.84 pg/mL (N 2.3-4.2 pg/mL), TSI <0.1 IU/L (0-0.55 IU/L), TRAb <1.1 IU/L (N 0-1.75 IU/L), anti-microsomal antibody <8 IU/mL (N 0-24 IU/mL), anti-thyroglobulin <1 IU/mL (0-0.9 IU/mL). Nuclear medicine uptake scan showed abnormally low 24 hr uptake indicative of thyroiditis in the setting of clinical and biochemical hyperthyroidism. MRI pituitary with and without contrast revealed normal appearing pituitary gland. Patient was subsequently started on prednisolone 30mg in AM and 10mg in PM to treat for thyroiditis as well as secondary adrenal insufficiency likely secondary to hypophysitis. Patient had improvement in symptoms of dizziness on prednisolone. Conclusion: This case highlights the co-existence of endocrinopathies associated with immune checkpoint inhibitor use. Though thyroiditis and hypophysitis are very well associated with immune checkpoint inhibitor use, co-existence of thyroiditis and hypophysitis is rare. This case illustrates the importance of having high index of suspicion for co-existence of endocrinopathies in patients treated with immune checkpoint inhibitors.

Presentation: Friday, June 16, 2023
FRI240 Aspirin Induced Adrenal Hemorrhage: Rare Side Effect Of A Common Medication!
Authors: Qadeer Hafiza Abeera , Samkutty Reshma , Singh Vinita
Published: October 2023

Disclosure: H.A. Qadeer: None. R. Samkutty: None. V. Singh: None.

Introduction: Adrenal hemorrhage is a heterogeneous disorder with various clinical presentations. Bilateral adrenal hemorrhage can result in acute adrenal insufficiency that can be fatal. With the increasing use of DOAC, cases of anticoagulation therapy induced adrenal hemorrhage have been reported. We present a rare case of unilateral adrenal hemorrhage in a patient with pre-existing adrenal myelolipoma after using Aspirin. Based on our literature search, previously only two cases of Aspirin Induced adrenal hemorrhage in a stable adrenal mass have been reported. Case Presentation: 55-year-old male with history of stable 6.2 cm right adrenal gland myelolipoma, fatty liver disease and hypertension, recent use of 2 doses 81 mg Aspirin after receiving right shoulder replacement surgery presented to emergency department with acute onset right sided flank pain, constant, radiating to the back and right upper quadrant associated with an episode of vomiting. He was hemodynamically stable. Blood work showed normal electrolytes, liver function and renal function at baseline. Hemoglobin was stable around 10g/dL. CT scan abdomen/pelvis with contrast showed increase in the size of a previously stable adrenal myelolipoma to 12.9 x 15.6 cm with mass effect upon the liver. Acute hemorrhage was suspected with the blood extending beyond the margins of the mass into the right retroperitoneal space, displacing the right kidney. On admission, aspirin was discontinued. With absence of hemodynamic instability, normal electrolytes, and normal AM cortisol level of 11.9 mcg/dL, adrenal insufficiency was ruled out. Hormonal work up for hyperfunctioning adrenal tumor was performed that ruled out pheochromocytoma, Cushing syndrome and Primary Aldosteronism. With symptomatic improvement, absence of progression of adrenal hemorrhage on repeat CT scan of the abdomen/pelvis, patient was discharged home. He received IR guided embolization of the right superior adrenal artery and middle adrenal artery in the outpatient setting. Discussion: Spontaneous adrenal gland hemorrhage is a rare event. Bilateral adrenal hemorrhage is associated with acute adrenal insufficiency that can be fatal. Major risk factors for adrenal hemorrhage include anticoagulant therapy, heparin Induced thrombocytopenia, hypercoagulable state, trauma and sever sepsis. Here we have reported a rare case of adrenal gland hemorrhage with therapeutic dose of aspirin used after orthopedic surgery. Aspirin is a very commonly used medication and high index of suspicion is required to avoid this side effect as Immediate discontinuation of the medication is necessary to prevent progression of the disease. Conclusion: Aspirin use can be associated with progression of stable benign adrenal tumors by causing spontaneous hemorrhage. A high index of clinical suspicion is required for timely recognition of this side effect.

Presentation: Friday, June 16, 2023
FRI245 Non-classic CAH Presenting As Bilateral Adrenal Incidentalomas
Authors: Chin Yun Ann , Puar Troy , King Thomas
Published: October 2023

Disclosure: Y.A. Chin: None. T. Puar: None. T. King: None.

Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder. Non-classic CAH usually presents in late childhood or asymptomatic may remain undiagnosed. Adrenal incidentalomas have been reported as a presentation of CAH. Clinical Case: A 56-year-old man presented with a 4-day history of epigastric pain associated with chest discomfort and diaphoresis. There was no postural giddiness, vomiting, paroxysm or constitutional symptoms. He was a smoker, his parents were non-consanguineous and he had fathered 2 children. He was tachycardic at 114 bpm, but normotensive (129/89 mmHg) with no postural hypotension and no abnormal pigmentation. He had evidence of heart failure with bibasal crepitations and pedal oedema. Secondary sexual characteristics were normal and testicular volume was 15 mls bilaterally with no palpable mass.

CT abdomen showed grossly enlarged bilateral adrenal glands with heterogenous nodular appearance with several focal hypodense cystic components, with absolute washout <60%. Biochemistry was consistent with primary adrenal insufficiency (PAI); 8am serum cortisol 188 nmol/L, with peak cortisol post 250mcg synacthen of 195 nmol/L. Serum ACTH was elevated at 254.6 ng/L, aldosterone and renin were normal and 24hr urinary normetanephrine was mildly elevated at 1982 nmol/d (NR 600-1900 nmol/d). Echocardiography revealed severe global hypokinesia (EF 20%) but myocardial perfusion imaging was negative for ischemia.

In view of suspicion for tuberculosis, malignancy or infiltrative disease, CT guided adrenal biopsy was performed. Histology showed hyperplastic adrenal cortex with lipofuscin pigments, focal lymphohistiocytic infiltrates. No lymphoplasmacytic infiltrate with IgG 4 plasma cells, granuloma, malignant cells or amyloid deposits were seen. Serum 17-OHP level later came back elevated at 39.7 nmol/L (NR 1.8-10.4 nmol/L). DNA sequencing of CYP21 revealed compound heterozygous mutations in c.292+1G>A and c.518T>A, both of which have been reported to be causative of CAH. He was transitioned from stress dose to physiological glucocorticoid replacement and ACTH normalised on subsequent outpatient visits. Follow up imaging after 6 months and 2 1/2 years revealed no change in size or morphology of the adrenal glands. Follow up echocardiography showed no improvement in ejection fraction despite intensive heart failure treatment. Conclusion: Nodular adrenal hyperplasia is well described among CAH individuals, especially in those with inadequate glucocorticoid replacement and chronically elevated ACTH levels. There was no change in size of the adrenal lesions despite adequate glucocorticoid replacement. Improvement of cardiac function with glucocorticoid replacement has been reported in paediatric patients with CAH, but our case did not show any improvement on serial echocardiography.

Presentation: Friday, June 16, 2023
FRI249 New Onset Heart Failure In A Patient With Rapidly Progressive Adrenocortical Carcinoma
Authors: Peeples James , Shu Sharon , Romo Karina G , Tereul Jeremy , Grissett Bryan Benjamin
Published: October 2023

Disclosure: J. Peeples: None. S. Shu: None. K.G. Romo: None. J. Tereul: None. B.B. Grissett: None.

Background: Adrenocortical carcinomas (ACC) are rare, relatively large (>4cm), lipid-rich, and often aggressive tumors. They may be functional, which typically presents as Cushing’s syndrome and/or virilization, or non-functional, which typically presents as an abdominal mass or incidental finding. They occur in two peak incidences: at the first decade of life and between 40-50 years of age. Over half of adult patients with ACC present with an advanced tumor stage. This case describes a young man with new onset heart failure and adrenal mass with metastases who was found to have biopsy-confirmed ACC. Clinical Case: A 20-year-old man with a history of cigarette smoking and marijuana use, but otherwise in prior good health, presented as a transfer for new onset heart failure in the setting of hypertensive emergency (SBP 260s), and CT findings of left adrenal mass, with multiple lung and liver masses. He noted 2 months of rapidly progressive weight gain, easy fatigability, dyspnea on exertion, and leg swelling. Exam revealed central adiposity with abdominal striae, bilateral clavicular and cervical fat pad, and bilateral lower extremity swelling. Investigations revealed hypercortisolism and ventricular ejection fraction 20-25%. Liver mass biopsy revealed metastatic ACC. Family history was significant for multiple members with early onset hypertension and congestive heart failure, including the death of maternal grandmother at age 40. The patient was initially managed in the ICU with an etomidate drip for adrenal suppression. Cortisol levels appropriately decreased to goal. Additionally, he started IV dexamethasone while inpatient. He was discharged once euvolemic on PO furosemide and follow-up was scheduled with cardiology, oncology, and endocrinology. At discharge, he transitioned to PO hydrocortisone (HC) and was placed on trimethoprim/sulfamethoxazole for PJP prophylaxis, doxazosin, and ketoconazole. He also started mitotane for his cancer treatment, with HC to prevent adrenal insufficiency while on mitotane. Subsequently, he started and failed carboplatin plus etoposide palliative chemotherapy with a continued increase in adrenal mass size. Now, he is on second line pembrolizumab with an ECOG score of 2. Conclusion: ACC is a rare and often aggressive tumor that should be considered in the setting of hypercortisolism and cushingoid features. This is particularly important for patients with a relatively unremarkable history and new onset heart failure with dyspnea on exertion. In these cases, mitotane can be used for hypercortisolism associated with ACC. Unfortunately, these tumors are usually diagnosed when they have already progressed to a late stage, and the prognosis for ACC is poor.

Presentation: Friday, June 16, 2023
FRI250 Dual Aldosterone And Cortisol Secreting Adrenal Cortical Carcinoma: Pre- And Perioperative Evaluation And Management
Authors: Rosenberg Rebecca , Clay Michael R , Raeburn Chris , Wierman Margaret E
Published: October 2023

Disclosure: R. Rosenberg: None. M.R. Clay: None. C. Raeburn: None. M.E. Wierman: None.

Representing 0.3% of all adrenal tumors, adrenal cortical carcinoma (ACC) is a rare and understudied disease. It is estimated that 60% of patients with ACC present with hormone excess syndromes, while the remainder present incidentally or with compressive symptoms from tumor invasion. ACC presentation with a combination of hormonal excess syndromes from different adrenal zones is rare and only described previously in four case reports. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new onset hypertension and hypokalemia during a primary care visit. On hormonal evaluation, he was found to have evidence of hyperaldosteronism and ACTH-independent cortisol excess (aldosterone 28.2ng/dL, plasma renin activity 0.1ng/mL/hr, and overnight 1mg dexamethasone suppression test cortisol of 13ug/dL). Imaging revealed a 2.7 x 3.1 x 3.5cm left adrenal mass suggestive of an adenoma. He underwent laparoscopic adrenalectomy and required glucocorticoid replacement for adrenal insufficiency post-operatively. Pathologic review of the gross specimen showed a sizable neoplasm measuring 6.5 x 3.0 x 2.5 cm, much larger than on CT imaging. Microscopic review showed stage T2N0M0 ACC with modified Weiss score of 6 and 68 mitoses per 50 hpf, indicative of aggressive disease. The patient’s hypokalemia resolved post-operatively, and glucocorticoids were tapered within a month. The mechanism of dual aldosterone/cortisol secretion is hypothesized to be due to overlap between genes coding for 11β-hydroxylase and aldosterone synthase, resulting in a chimeric gene with increased secretion of both enzymes, and, therefore, both hormones. Though dual secretion is rare, this case report stresses the importance of screening for cortisol excess, and hyperaldosteronism in the correct clinical setting, in patients with adrenal masses detected on imaging. A complete biochemical hormone evaluation should be performed regardless of the discovery of other hormone secreting syndromes, ideally preoperatively with a multidisciplinary team including endocrinology. The medical team should continue to bear in mind that the existence of one hypersecretory syndrome does not rule out the presence of a second or third, and hormonal excess syndromes may affect patient outcomes peri- and postoperatively.

Presentation: Friday, June 16, 2023
FRI251 A Combination Of Klinefelter Syndrome And The Classic Form Of Congenital Dysfunction Of The Adrenal Cortex: Clinical Case
Authors: Volkova Natalia I
Published: October 2023

Disclosure: N.I. Volkova: None.

Introduction: Congenital adrenal hyperplasia (CAH) is a defect in one of the enzymes or transport proteins involved in the synthesis of cortisol in the adrenal cortex. Virile form of CAH is characterized by cortisol deficiency and hyperandrogenism. Klinefelter syndrome is one of the most frequent chromosomal diseases leading to the development of primary hypogonadism. The manifestation of these two diseases in one patient causes difficulties in diagnosis and medical treatment that leads to adverse consequences. Clinical Case: A 43-years-old patient consulted a physician complaining about the lack of erections for 4 years, breast enlargement. From anamnesis, it is known: that the patient at the age of 2 years and 8 months based on experienced growth of pubic hair, decreased level of 17-ketosteroids in the urine and genetic analysis diagnosis of CAH, virile form was suspected. Prednisone 5 mg daily was prescribed. At the age of 5, based on phenotypic features and karyotyping Klinefelter Syndrome (XXY) was diagnosed. At the age of 13, stimulating hormonal chorionic gonadotropin drug with only one course of 10 injections was prescribed. At the age of 18, the patient independently canceled the use of prednisone. Further, he did not receive medication therapy for CAH and Klinefelter syndrome. At the age of 42, adrenal CT revealed formation of the left adrenal gland. High levels of aldosterone and renin were detected. A diagnosis of left adrenal aldosteroma was made and a left-sided adrenalectomy was performed. Histological examination diagnosis of aldosteroma did not confirmed. On physical examination, BMI 30 kg/m2, genoid type of obesity, right testicle is not palpated, left testicle is dense, reduced in size. Small penis size.Laboratory examination revesled decreased level of total testosterone, normal level of SHBG, LH and FSH. Ultrasound of the scrotum organs revealed as well decrease in the size of the testicles and appendages, a volumetric formation of the right testicle, suspicious of tumor. Thus, diagnosis of CAH, virile form and Klinefelter syndrome, primary hypogonadism, right-sided cryptorchidism was confirmed. Hydrocortisone 30 mg daily was prescribed. Hormone replacement therapy with testosterone preparations was not prescribed until surgical treatment of neoplasm of the right testicle will be performed. Conclusion: We have demonstrated a combination of two endocrine pathologies and serious mistakes were made in the management of this patient that requires a multidisciplinary approach, which improves the prognosis and quality of life of these patients.

Presentation: Friday, June 16, 2023
FRI260 Adrenal Hemangioma, Mimicker Or Malignant?
Authors: Pham Christopher , Chiu Christine Elizabeth , Barnett Braden
Published: October 2023

Disclosure: C. Pham: None. C.E. Chiu: None. B. Barnett: None.

Background: Adrenal hemangioma is a rare condition that can mimic other adrenal pathologies. Clinical Case: A 49 year old male with history of heart failure presented with cardiogenic shock requiring inotropes and heart transplant evaluation. On CT patient was noted to have a 2.2 cm left adrenal nodule containing calcifications. Initial tests had indeterminate 1 mg overnight DST, normal plasma free metanephrines and elevated plasma free normetanephrines 2.06 nmol/L (0-0.89 nmol/L). PRA was 22.82 ng/mL/hr (0.25-5.82 ng/ml/hr) with aldosterone 10.8 ng/dL (<16 ng/dL) on spironolactone. 24 hour urine tests showed normal free cortisol 9.8 mcg/24hr (4-50 mcg/24hr) and elevated total metanephrines at 1245 mcg/24hr (182-739 mcg/24hr), metanephrines at 303 mcg/24hr (58-283 mcg/24hr), and normetanephrines at 942 mcg/24hr (88-649 mcg/24hr). Adrenal CT demonstrated HU of 59 units on noncontrast phase, with -86.7% absolute washout and -17.6% relative washout. I-123 MIBG Scan was obtained with no radiotracer uptake noted. Patient underwent laparoscopic adrenalectomy for definitive diagnosis and was found to have adrenal hemangioma with CD31 and ERG with hemosiderin laden macrophages on pathology. Adrenal hemangioma is rare and can mimic other adrenal pathology. Most patients present with abdominal symptoms such as flank pain or are found to have an adrenal incidentaloma on imaging. CT findings are associated with heterogenous internal structure, peripheral patchy enhancement, or calcifications, which are also seen in malignancy and pheochromocytoma. In all cases, HU if recorded are noted to be >10 on the unenhanced phase and <60% absolute washout. In one case series of 52 adrenal hemangiomas, only 3 patients had positive biochemical tests and on average were 11 cm in size. Formal diagnosis is made pathologically. Treatment for adrenal hemangioma is typically resection for symptomatic relief, with some patients with small lesions electing to observe. In all surgical cases reviewed in a case series adrenalectomy was pursued as opposed to needle biopsy due to large size of lesion and concern for possible malignancy. In this specific case, biochemical testing was falsely positive given the patient’s presentation of cardiogenic shock and inotropes causing elevated catecholamine levels and given imaging findings could not fully rule out pheochromocytoma. Given the small size of lesion, the patient in a non-transplant setting likely could have pursued close observation as opposed to resection. Conclusion: Adrenal hemangioma can have imaging characteristics that can mimic several other adrenal pathological conditions, such as malignancy or pheochromocytoma. Treatment through surgical management is likely not necessary in patients with hemangioma, though would be important in ruling out other adrenal pathology.

Presentation: Friday, June 16, 2023