bluuebunny/crossref_metadata_2025_split huggingface dataset:
12564 A Rare Case Of Pembrolizumab Induced Secondary Adrenal Insufficiency
Authors: Escano Volquez Lorena , Desai Prarthana 
Published: October 2024

Abstract
Disclosure: L. Escano Volquez: None. P. Desai: None.
Pembrolizumab is an immune check-point inhibitor that blocks the PD1 receptor and is currently used in the treatment of a vast variety of malignancies. Despite adrenal insufficiency (AI) already being documented as a rare but potential side effect, its diagnosis is usually delayed due to vague presentation, increasing the risk of deleterious outcomes. We present a case of secondary AI while on pembrolizumab in which diagnosis was delayed due to unspecific clinical picture.This is a 66-year-old male who presented to the hospital with decreased appetite, nausea and generalized weakness. Patient was seen a month prior with similar symptoms which were thought to be secondary to poor oral intake in the setting of underlying malignancy. Medical history remarkable for squamous cell carcinoma of the skin with recent lung metastasis for which he was started on pembrolizumab a year ago. On arrival to the emergency department, patient was hypertensive with BP 144/68 mmHg, HR 88, and RR 15. Orthostatic vitals were positive. Physical examination otherwise unremarkable. Laboratory tests revealed mild hypernatremia of 147, potassium of 4.7, chloride 108, HCO3 18, anion gap 21, BUN 33, elevated creatinine 1.62 and elevated beta-hydroxybutyrate 5.4. EKG revealed sinus rhythm. Patient was admitted for further evaluation of orthostasis and starvation ketosis. Initial management included IV fluids and Midodrine. However, patient continued to have episodes of orthostatic hypotension. Lack of improvement of symptoms led to further workup which revealed low AM cortisol of 1.0 and a low ACTH level &lt;3.0 pg/ml, concerning for secondary adrenal insufficiency. Patient was administered Solu-Medrol 40 mg IV before being transitioned to a daily hydrocortisone regimen with subsequent improvement of symptoms. Pembrolizumab induced AI is a very rare event. It is estimated that the incidence approaches 1% and symptoms can develop at any time throughout treatment. Despite its low incidence, it can be life-threatening if not diagnosed and treated promptly. However, given its very heterogeneous and vague clinical presentation, a prompt diagnosis can be difficult. The clinical course of our patient and subsequent resolution of symptoms after appropriate treatment was started, supports the diagnosis of pembrolizumab induced adrenal insufficiency after a year of initiating treatment. This patient had prior hospitalizations and office visits with symptoms that are usually already present in individuals with underlying malignancy, which resulted in underestimation of his symptoms. This case highlights the importance of always considering AI as a potential adverse effect of immune check-point inhibitors. This will ensure a prompt diagnosis and treatment of an endocrine disorder that could otherwise lead to deleterious outcomes if left untreated.
Presentation: 6/1/2024
8733 Adrenal Crisis In A Patient Diagnosed With Primary Adrenal Insufficiency Following COVID-Vaccination
Authors: Hayat Aamir , Aslam Noreena 
Published: October 2024

Abstract
Disclosure: A. Hayat: None. N. Aslam: None.
Primary adrenal insufficiency, or Addison's disease, is characterized by the inadequate production of cortisol and often requires lifelong hormone replacement therapy. COVID-19 vaccines have demonstrated overall safety, but this report explores a unique case of adrenal crisis post-vaccination in a patient with pre-existing adrenal insufficiency. A 38-year-old female, diagnosed with primary adrenal insufficiency, received her second dose of a COVID-19 vaccine. Within 48 hours after vaccine administration , she presented to the emergency department with severe fatigue, hypotension, nausea, and abdominal pain. Clinical examination and laboratory tests confirmed an adrenal crisis, with markedly decreased cortisol levels, hyponatremia, hyperkalemia, and an elevated ACTH level. The patient was promptly treated with intravenous hydrocortisone and saline fluids. Close monitoring of vital signs and cortisol levels was maintained, with a gradual tapering of hydrocortisone as the patient's symptoms improved. The importance of stress-dose steroids during illness or vaccination in patients with adrenal insufficiency is underscored. This case highlights that the Healthcare providers should be aware of this rare but severe complication and consider appropriate monitoring and stress-dose steroid coverage in susceptible populations.
Presentation: 6/3/2024
7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma
Authors: Aboishava Lizaveta , Pareek Ashutosh , Mertens Avalon , Erokhin Aleksandr 
Published: October 2024

Abstract
Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None.
Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (&lt;5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms.
Presentation: 6/3/2024
6436 Adrenal Venous Congestion Clinically Mimicking Carcinoma In A Large Degenerated Adrenocortical Adenoma
Authors: Ishiwata Kazuki , Suzuki Sawako , Watanabe Suzuka , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro 
Published: October 2024

Abstract
Disclosure: K. Ishiwata: None. S. Suzuki: None. S. Watanabe: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None.
Introduction: A large heterogenous adrenal tumor is often malignant. Only eight reported cases of adrenal adenoma harboring hemorrhage or venous thrombosis have been reported but their details not. We encountered a case of large degenerated adrenocortical adenoma harboring adrenal venous congestion mimicking adrenocortical carcinoma. Case: Adrenal tumor was incidentally detected in a 71-year-old woman with a history of hypertension, dyslipidemia, and osteoporosis in her regular health check-up. Abdominal CT and MRI demonstrated a heterogenous mass measuring 7.6 cm with peripheral enhancement in the left adrenal gland. [1]3[1]I-adosterol scintigraphy revealed accumulation only in the left tumor margins with no accumulation in [1]8F-FDG-PET scan. Results of endocrinologic evaluation were consistent with subclinical Cushing syndrome. The large size and heterogeneous nature of the mass clinically suggested adrenocortical malignancy, and left laparoscopic adrenalectomy was subsequently performed. The resected left adrenal lesion was encapsulated and measured 6.5 x 6.3 x 5.8 cm appearing almost black and partially yellow on the cut surface. Microscopically, the nodule was composed of SF-1 positive, clear cortical cells with abundant hyaline stroma containing numerous dilated veins with CD31/34-positive endothelial cells, and no foci of necrosis or hemorrhage were detected. The tumor cells above were positive for steroidogenic enzymes including CTP17, HSD3β and CYP11B1 but negative for CYP11B2. Ki-67 labeling index was &lt;2% in the tumor. The criteria of Weiss (0 out of 9) revealed that the tumor was cortisol-producing adrenocortical adenoma. Discussion: In this case, clusters of SF1-positive cortisol producing adrenocortical adenoma cells were present in the hyalinized stroma containing many dilated blood vessels. These findings indicated that those histological features were caused by ischemic degeneration due to intratumoral circulatory disturbance, which clinically simulated adrenocortical carcinoma. Conclusion: We have experienced a very rare case of cortisol-producing adrenocortical adenoma with adrenal venous congestion, resulting in marked enlargement of the lesion.
Presentation: 6/3/2024
7805 Adrenocortical Carcinoma - A Tertiary Center's Recent ∼10-Year Experience
Authors: Osher E , Tordjman K M , Sofer Y , Stern N , Klausner J , Lahat G , Lubezky N , Goykhman Y , Sagie B , Ravit G , Asaf A , Rivka K , Ido W , Greenman Y 
Published: October 2024

Abstract
Disclosure: E. Osher: None. K.M. Tordjman: None. Y. Sofer: None. N. Stern: None. J. Klausner: None. G. Lahat: None. N. Lubezky: None. Y. Goykhman: None. B. Sagie: None. G. Ravit: None. A. Asaf: None. K. Rivka: None. W. Ido: None. Y. Greenman: None.
Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Prospective randomized controlled studies to evaluate the optimal treatment modalities are limited. Therefore, retrospective studies are needed. The aim of the study is to describe and summarize additional data and knowledge on treatment modalities in a tertiary medical center treating patients with ACC by a multidisciplinary expert team. Methods: A retrospective study. Results: The study cohort included 42 subjects (57% females), followed for a median of 26 (range 0.3-237) months. The mean age at diagnosis was 54±17 years; 60% of tumors were functioning, 57 % were cortisol-secreting, 41% were androgen-secreting, 12% aldosterone-secreting, and 45% were co-secreting. ENSAT stage at diagnosis was stage 1 in 19%, stage 2 in 26%, stage 3 in 24% and stage 4 in 29%. Eighty-eight % of patients underwent surgery; residual disease was in 21% post surgery. Treatment with mitotane was initiated in 62% of patients, reaching a mean maximal dose of 3.1 ±2 grams/day. Oncologic pharmacological treatment (Chemotherapy, TKI, Immunotherapy) and/or radiation were given in 50 % and 21%, respectively. In 14 /42 patients, genetic evaluation was done, in most cases, no target for treatment was found. 52% of patients died during follow-up; all cohort median time to death was 31(range 0.3-237) months. Time to death longer than 31 months was also seen in advanced disease stage 3- 3/9(33%) and stage 4-4/11(36%). Except association between mitotane and prolonged time to death (p=0.013), no other factors (age, gender, surgery, radiation, residual disease functional status), were associated with prolonged survival. Conclusions: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients with advanced disease achieving more prolonged survival. Further characterization of these patients may improve our understanding of the biology and treatment of this rare disease.
Presentation: 6/2/2024
8627 Viral Hormones: The Role Of Viral Insulin/IGF-1 Like Peptides In Host-Pathogen Interactions
Authors: Chuard A , Nesarajah K , Danazumi K , Reiners K , Zhang F , DiMarchi R , Altindis E 
Published: October 2024

Abstract
Disclosure: A. Chuard: None.
Viruses, encode proteins that are similar to host proteins to manipulate the host. Until our recent discovery of viral hormones, examples of viral mimicry were limited to immunomodulatory proteins and growth factors. We recently showed that six viruses in Iridoviridae family encode genes mimicking human insulin and IGF-1. We previously chemically synthesizing these viral insulin/IGF-1 like peptides (VILPs) and showed that VILPs can bind to human insulin and IGF-1 receptor and further stimulate post-receptor signaling. VILPs also stimulate glucose uptake and proliferation in mammalian cells and lower the blood glucose in mice. Originally, VILP-carrying viruses were isolated from fish; however, the role of VILPs in viral pathogenesis is not studied in depth. Here, we examined the effects of Grouper Iridovirus (GIV, one of the VILP carrying viruses) infection and GIV-VILP on host insulin/IGF signaling system using fish cells.To this end, we chemically synthesized GIV-VILP in its single chain (sc, IGF-1 like) and double chain (dc, insulin-like) forms. Stimulation of grouper kidney (GK) and AB9 zebrafish cells with these peptides, insulin and IGF-1, showed that IGF-1 was the most potent ligand in these cells indicating an abundance of IGF-1 receptor (IGF1R). Further, both forms of the VILPs were as potent as insulin in its activity on receptor phosphorylation and post-receptor signaling. Examining the viral kinetics, we also showed that GIV32 gene (encoding GIV VILP) is an early viral gene in both cell types. Virion analysis through mass spectrometry indicated that VILPs are not viral structural proteins. On the other hand, analysis of the supernatant from infected cells indicated that VILPs are secreted peptides during the viral cycle. Our results with supernatant transfer experiments from infected cells to uninfected cells support the same conclusion that VILPs are secreted. The secreted VILPs initiate autophosphorylation of IGF1R and/or insulin receptor (IR), consequently triggering downstream cellular signaling and metabolism. Through the use of specific inhibitors for each receptor, we illustrated that IR signaling is crucial for GIV viral replication. Surprisingly, inhibition of IGF1R increased viral replication and we are currently examining potential inhibitory effects of GIV VILP. Furthermore, VILPs appear to exert a biased effect on the AKT pathway compared to the Erk pathway. Furthermore, the inhibition of the AKT pathway significantly reduces GIV viral replication. In summary, our findings reveal that GIV-VILP is actively produced during infection and contributes to the viral replication. To our knowledge, VILPs are the first hormone-mimics characterized in viral replication. Elucidating the role of VILPs in host-pathogen interactions, we propose a novel viral pathogenesis mechanism where viruses mimic host hormones to manipulate the host's endocrine system.
Presentation: 6/3/2024
12389 Viral Insulin/IGF-1-like Peptides: A New Dimension In Understanding The Insulin/IGF System
Authors: Chrudinova M , Chuard A , Zhang F , Dogru Y D , De Meyts P , Kim J K , Kirk N , Jiracek J , DiMarchi R D , Altindis E 
Published: October 2024

Abstract
Disclosure: M. Chrudinova: None. A. Chuard: None. F. Zhang: None. Y.D. Dogru: None. P. De Meyts: None. J.K. Kim: None. N. Kirk: None. J. Jiracek: None. R.D. DiMarchi: None. E. Altindis: None.
Viral Insulin/IGF-1-Like Peptides: A New Dimension in Understanding the Insulin/IGF System Martina Chrudinova, Aurelien Chuard, Dogus Dogru, Nicholas Kirk, Pierre De Meyts, Jason Kim, Richard Di Marchi, Jiri Jiracek, Emrah AltindisMammals have separate insulin and IGF-1 receptors, and in most species, one insulin and two IGFs interact with them. The mammalian Insulin receptor (IR) primarily controls metabolism, while the insulin-like growth factor-1 (IGF-1) receptor (IGF1R) regulates cell apoptosis, growth, and prenatal and postnatal differentiation. Despite their distinct functions, due to high structural similarity, insulin and IGF-1 can bind to each other's receptors with different potencies. However, the presence of viral insulin/IGF-1-like peptides (VILPs) and their effects on mammalian cells were unknown until our recent discovery.For the first time, we demonstrated that viruses possess active gene products that mimic human insulin and IGF-1. These VILPs are approximately 30-50% identical to human insulin and IGF-1 and exhibit atypical effects on the insulin/IGF system. Our initial studies provided insights into VILPs and this complex signaling system: •Introducing the novel concept of a system of viral hormones and viral insulins. •Identifying VILPs in six different Iridoviridae viruses and discovering sequences of these viruses in human samples. •Providing evidence that all VILPs bind to human IR and IGF-1 receptors and that agonist VILPs can stimulate downstream signaling. •Demonstrating that agonist VILPs can increase glucose uptake in vitro and in vivo and have tissue-specific and long-lasting effects. •Showing the expression of VILPs during viral infection and their stimulation of insulin/IGF signaling. •Identifying Mandarin fish ranavirus (MFRV) and Lymphocystis disease virus-1 (LCDV-1) VILPs as potent inhibitors of human IGF1R. To the best of our knowledge, these are the first peptide inhibitors of the IGF1R. •CryoEM studies revealed that two LCDV-1 VILPs bind to IGF1R and lock it. •Unlike the evolution of host insulin/IGFs, these unique characteristics of the VILPs are most likely acquired as a result of distinct co-evolution in viral genomes to facilitate viral pathogenesis in the host.In conclusion, VILPs, as active members of the insulin/IGF superfamily, possess unique characteristics. Our findings on the characterization of the VILPs and their distinct functions open new avenues for a deeper understanding of the insulin/IGF-1 signaling system. Furthermore, VILP research will guide us in designing specific and potent agonists and antagonists of the IR/IGF1R system, with the potential to lead to new therapeutic strategies for a wide range of human diseases.
Presentation: 6/2/2024
8192 A Two-Cycle Clinical Audit Testing Inpatient Management Of Hypophosphatemia In A UK District Hospital
Authors: Porto J , Ssemmondo E , Obike N , Abobaker A , March R , Tun N , Pawlak T 
Published: October 2024

Abstract
Disclosure: J. Porto: None. E. Ssemmondo: None. N. Obike: None. A. Abobaker: None. R. March: None. N. Tun: None. T. Pawlak: None.
Objective: A clinical audit was conducted to assess if there was any improvement in management of hypophosphatemia among patients admitted to the medical wards using the local Trust protocol, following structured edcational sessions to the junior doctors covering medical wards. Design and methodology: The 2 cycles of the audit were conducted between March 2020 and September 2021 in Scarborough district Hospital. The clinical notes of 52 patients (20 in the first cycle and 32 in the re-audit) with hypophosphatemia were reviewed. These were identified using the electronic laboratory results of patients within the study period. The aspects of the trust protocol for management of hypophosphatemia that were audited; documentation of symptoms associated with low phosphate levels, cardiac monitoring in severe hypophosphatemia, identification of the likely cause of hypophosphatemia, the presence or absence of associated acute kidney injury (AKI) and initiation of phosphate replacement. The results of the first audit were presented at the local hospital clinical governance meeting (August 2020). Following this, 2 teaching sessions and 2-case based discussion on hypophosphatemia were organised for all the doctors in the department of medicine. The re-audit was subsequently conducted after the fourth teaching session. The proportions of each audited item were compared between the first audit and the re-audit using Fisher exact probability test. Results:25% of patients in the first audit had severe hypophosphatemia compared to 28% in the re-audit. In patients with severe hypophosphataemia, only 33.3% had cardiac monitoring during the re-audit cycle compared to 60% in the first cycle, and the difference was not statistically significant (p=0.58). There was significant improvement in the documentation of symptoms of hypophosphataemia amongst inpatients during the re-audit cycle compared with the initial cycle; 62.5% vs only 10% (P 0.002). Most patients had an underlying cause of the hypophosphatemia identified (80% and 62.5%-first and second cycle respectively). AKI was associated with hypophosphataemia in 15% & 34.4% (P 0.2) in the first and second cycles respectively. Despite low phosphate levels, 25% and 28.1% at the initial audit and the second cycle respectively did not receive any form of phosphate replacement. Conclusion: The two-cycle clinical audit showed that the teaching sessions on management of hypophosphatemia increased the awareness of the importance to document whether the patients were symptomatic or asymptomatic following the drop in their phosphate levels, which can help to identify patients at risk of developing complications, such as cardiac arrythmias. However, these sessions were not sufficient to improve overall management of patients with low phosphate levels.
Presentation: 6/1/2024