Relative Adrenal Insufficiency Research Articles

Liver cirrhosis as a multisystem disease

In recent years, the pathophysiological concept of decompensated liver cirrhosis has undergone significant changes. Until a few years ago, the focus of pathophysiological considerations was on the hyperdynamic circulation resulting from portal hypertension. In recent years, emerging data suggests that increased bacterial translocation leading to systemic inflammation plays an important role in patients with decompensated liver cirrhosis. This inflammation affects a variety of extrahepatic organs. Nowadays, liver cirrhosis is considered not only a condition confined to the liver but rather an inflammatory-triggered multisystem disease. The existing inflammation serves as the common pathophysiological explanation for the diverse impact of liver cirrhosis on several extrahepatic organs. It plays a significant role in the development of conditions such as hepatorenal syndrome, cirrhotic cardiomyopathy, hepatopulmonary syndrome, hepatic encephalopathy, and even in the emergence of cirrhosis-associated relative adrenal insufficiency. These new pathophysiological insights hold clinical significance as they influence the prophylaxis and treatment of patients with decompensated liver cirrhosis.

Serum Cortisol Levels in Children with Catecholamine-Dependent Shock – A Prospective Observational Study

Pediatric septic shock poses a significant challenge in ICUs worldwide, with high mortality and morbidity rates despite medical advancements. Early recognition and aggressive management are crucial. Resistance to standard therapies in some cases suggests potential adrenal insufficiency, particularly relative adrenal insufficiency (RAI), though research is limited. This study aimed to assess adrenal insufficiency prevalence in pediatric septic shock by evaluating basal serum cortisol levels in 49 children aged 1 month to 12 years admitted to the PICU. Results showed a significant 41% prevalence of adrenal insufficiency, correlating with prolonged critical care needs. Despite increased interventions, mortality rates didn't notably differ between groups. Recognition of adrenal insufficiency is vital due to its association with extended critical care requirements. Further research, including stimulation tests and trials, is needed to distinguish absolute and relative adrenal insufficiency and assess potential benefits of steroid supplementation. This study underscores the importance of comprehensive management strategies incorporating adrenal function assessment in improving outcomes for critically ill children with septic shock.

Adrenal insufficiency in liver diseases - pathophysiology and underlying mechanisms.

Relative adrenal insufficiency (RAI) is common in critically ill patients with cirrhosis, but it has been also documented in non-critically ill patients. Its pathophysiology is complex and not well understood yet. In this review, we aimed to present potential mechanisms and causal pathways implicated in the pathogenesis of RAI in cirrhosis. There is accumulating evidence supporting a suboptimal baseline adrenal function in cirrhosis mainly due to decreased cortisol synthesis and metabolism rates from the adrenal gland. Apart from this peripheral impairment, more recent studies suggest that there is a greater defect in the central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis (hypothalamus/pituitary gland). Pro-inflammatory mediators, which are elevated in cirrhosis, have been also implicated through suppression of the HPA axis, decrease in cortisol synthesis and tissue glucocorticoid resistance. All abovementioned support the hepatoadrenal syndrome hypothesis that during episodes of acute decompensation there is suboptimal adrenocortical response that leads to worse outcomes. In conclusion, the complex pathophysiology of adrenal dysfunction in cirrhosis has not been fully elucidated yet and further research is needed in order to better understand this rather common entity in cirrhosis.

Relative Adrenal Insufficiency in Full-Term and Preterm Neonates with Neonatal Sepsis

Background: Neonatal sepsis is the third most common cause of death in newborns and a significant issue for public health, particularly in developing nations. This study aimed to assess the hypothalamic-pituitary-adrenal axis (HPA) response in full-term and preterm newborns diagnosed with neonatal sepsis in the neonatal intensive care unit (NICU).
 Methods: This cross-section observational research was done on neonates who were categorized into two main groups Group I: Sepsis neonates who were further subdivided into two groups according to the gestational age into 30 full-term neonates with neonatal sepsis and 30 preterm neonates with neonatal sepsis. Group II: Included 30 healthy control neonates.
 Results: HSS score and C reactive protein (CRP) level were correlated with serum cortisol level at (9 am: r=-0.273, P<0.035 and r=-0.447, P<0.001), (9 pm: r=-0.447, P<0.001and r=-0.477, P<0.001) ACTH at (9 am: r=-0.314, P<0.015 and r=-0.377, P<0.003) and at (9 pm: r= -0.362, P<0.005 and r=-0.448, P<0.001) and cortisol level post ACTH stimulation (r=-0.345, 0.007 and r=-0.497, P<0.001) respectively. Regarding inotropes, sepsis type and oxygen support there was significant difference between both groups.
 Conclusions: 75% of the patients we evaluated with neonatal sepsis had relative adrenal insufficiency (RAI). ACTH and Cortisol values were correlated to CRP and HSS score as an inflammatory marker. This reflects suppressed HPA status in this critical clinical condition.

Cytokine Release Syndrome with Relative Adrenal Insufficiency Induced by Ipilimumab and Nivolumab Combination Therapy for Clear Cell Renal Cell Carcinoma.

Combination therapy with ipilimumab and nivolumab is indicated for many types of cancers; however, several patients experience immune-related adverse events (irAEs). We herein report a case of cytokine release syndrome (CRS) in a 63-year-old woman with stage IV left clear cell renal cell carcinoma. Our patient developed CRS while taking prednisolone, 43 days after the start of ipilimumab and nivolumab administration. The patient was treated with steroid pulse therapy, which improved the symptoms of shock and respiratory failure. Increased vascular permeability and relative adrenal insufficiency are considered to be the main pathogeneses. The early administration of high-dose steroids is crucial as a replacement for corticosteroids.

Low Urinary Free Cortisol as a Risk Factor for Patients with Variceal Bleeding.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens' equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child-Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

1153P Incidence and characteristics of immunotherapy related adrenal insufficiency in a monocenter, pan-cancer cohort of 4314 patients

1153P Incidence and characteristics of immunotherapy related adrenal insufficiency in a monocenter, pan-cancer cohort of 4314 patients

Relative Adrenal Insufficiency Is a Risk Factor for Pediatric Sepsis: A Proof-of-Concept Study.

Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry-induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

Sepsis and Adrenal Insufficiency.

In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice.

Changes in Cortisol Secretion and Corticosteroid Receptors in COVID-19 and Non COVID-19 Critically Ill Patients with Sepsis/Septic Shock and Scope for Treatment.

Sepsis is associated with dysregulated cortisol secretion, leading to abnormal levels of cortisol in the blood. In the early stages of the condition, cortisol levels are typically elevated due to increased secretion from the adrenal glands. However, as the disease progresses, cortisol levels may decline due to impaired adrenal function, leading to relative adrenal insufficiency. The latter is thought to be caused by a combination of factors, including impaired adrenal function, decreased production of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by the hypothalamus and pituitary gland, and increased breakdown of cortisol. The dysregulation of cortisol secretion in sepsis is thought to contribute to the pathophysiology of the disease by impairing the body's ability to mount an appropriate inflammatory response. Given the dysregulation of cortisol secretion and corticosteroid receptors in sepsis, there has been considerable interest in the use of steroids as a treatment. However, clinical trials have yielded mixed results and corticosteroid use in sepsis remains controversial. In this review, we will discuss the changes in cortisol secretion and corticosteroid receptors in critically ill patients with sepsis/septic shock. We will also make special note of COVID-19 patients, who presented a recent challenge for ICU management, and explore the scope for corticosteroid administration in both COVID-19 and non-COVID-19 septic patients.

Relative adrenal insufficiency in liver cirrhosis: a common but often forgotten critical condition

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery

ObjectivesThe role of re-irradiation after salvage surgery for recurrent oral cavity cancer (OCC) is controversial. We evaluated the efficacy and safety of adjuvant toripalimab (PD-1 antibody) in this patient setting. Materials and methodsIn this phase II study, patients after salvage surgery with OCC occurring in an area of previously irradiated were enrolled. Patients received toripalimab 240 mg once every 3 weeks for 12 months, or combined with S-1 orally for 4–6 cycles. The primary endpoint was 1-year progression-free survival (PFS). ResultsBetween April 2019 and May 2021, 20 patients were enrolled. Sixty percent patients had ENE or positive margins, 80% were restaged as stage IV, and 80% were previously treated with chemotherapy. The 1-year PFS and overall survival (OS) were 58.2%, and 93.8%, respectively, for patients with CPS ≥ 1, which was significantly better than those of the real-world reference cohort (p = 0.001 and 0.019). No grade 4–5 toxicities were reported, and only one patient experienced grade 3 immune related adrenal insufficiency and discontinued treatment. The 1-year PFS and OS were significantly different for patients with CPS < 1, CPS 1–19 and CPS ≥ 20 (p = 0.011 and 0.017, respectively). The peripheral blood B cell proportion was also correlated with PD in 6 months (p = 0.044). ConclusionAdjuvant toripalimab or combine with S-1 after salvage surgery showed improved PFS compared with a real-world reference cohort in recurrent, previously irradiated OCC, and favorable PFS were observed in patients with a higher CPS and peripheral B cell proportion. Further randomized trials are warranted.

Acute adrenal crisis precipitated by thyroid storm in a patient with undiagnosed autoimmune polyglandular syndrome type 2.

Autoimmune polyglandular syndrome (APS) type 2 is characterized by the presence of Addison's disease (AD) along with autoimmune thyroid disease and/or type 1 diabetes. APS type 2 is known as Schmidt's syndrome when autoimmune adrenal insufficiency is associated with chronic lymphocytic thyroiditis. We report a very rare case of a 28-year-old female patient who had Schmidt's syndrome revealed by a thyroid storm (TS) concomitant with an acute adrenal crisis. The onset of AD resulted in a surgical emergency. The patient presented with cardiogenic shock and an acute abdomen. The precipitation factor was Hashitoxicosis presented as TS. This life-threatening condition was successfully reversed with aggressive medical therapy based on antithyroid drugs and intravenous glucocorticoids. This hyperthyroid phase lasted for a period of 8 months. The patient eventually developed hypothyroidism, suggesting that Hashimoto's thyroiditis was the most likely diagnosis. She was started on levothyroxine replacement therapy and remained euthyroid on levothyroxine. The case we describe had several diagnostic pitfalls that are discussed both at the start as well as during the evolution. Autoimmune diseases can appear concomitantly or succeed each other over time. The clinician must be vigilant to detect these diseases in time in order to avoid a misdiagnosis of a life-threatening emergency such as adrenal insufficiency or thyroid storm. Thyroid storm is an uncommon but life-threatening manifestation of hyperthyroidism. Diagnosis is dependent on clinical symptoms, and no specific laboratory tests are available. Glucocorticoids should be used in the treatment of thyroid storm because they have an inhibitory effect on peripheral conversion of T4 to T3. In patients who have severe thyrotoxicosis, especially in conjunction with hypotension, treatment with glucocorticoids has become standard practice because of the possibility of relative adrenal insufficiency or the possibility of undiagnosed Addison's disease. The differential diagnosis of hyperthyroidism can be challenging. Graves' disease can be discussed in view of the severity of the clinical presentation and the prolonged duration of the hyperthyroid phase. Hashitoxicosis is the initial hyperthyroid phase in chronic autoimmune thyroiditis. The hyperthyroid phase is always followed by definitive resolution, with persistent euthyroidism and no hyperthyroid relapses. Synthetic antithyroid drugs may be prescribed during the hyperthyroid phase of Hashimoto thyroiditis if the clinical presentation is severe and the duration of the hyperthyroid phase is prolonged.

The adrenal stress response is an essential host response against therapy-induced lethal immune activation.

Cytokine release syndrome (CRS) is a systemic inflammatory syndrome associated with infection- or drug-induced T cell activation and can cause multiple organ failure and even death. Because current treatments are ineffective in some patients with severe CRS, we set out to identify risk factors and mechanisms behind severe CRS that might lead to preventive therapies and better clinical outcomes in patients. In mice, we found that deficiency in the adrenal stress response-with similarities to such in patients called relative adrenal insufficiency (RAI)-conferred a high risk for lethal CRS. Mice treated with CD3 antibodies were protected against lethal CRS by the production of glucocorticoids (GC) induced by the adrenal stress response in a manner dependent on the scavenger receptor B1 (SR-BI), a receptor for high-density lipoprotein (HDL). Mice with whole-body or adrenal gland-specific SR-BI deficiency exhibited impaired GC production, more severe CRS, and increased mortality in response to CD3 antibodies. Pretreatment with a low dose of GC effectively suppressed the development of CRS and rescued survival in SR-BI-deficient mice without compromising T cell function through apoptosis. Our findings suggest that RAI may be a risk factor for therapy-induced CRS and that pretreating RAI patients with GC may prevent lethal CRS.

A STUDY ON IMPROVED PATIENT OUTCOMES IN SEPTIC SHOCK WITH USE OF HYDROCORTIS

Management of sepsis is a time critical procedure; the consequences of improperly managed sepsis and septic shock can cause multiple organ dysfunction and death. The aim of this study was to evaluate of the role of hydrocortisone. Ÿ Sepsis is dened as life-threatening condition causing multi-organ dysfunction by a dysregulated host response to infection. Septic shock is a subset of sepsis with circulatory and cellular or metabolic dysfunction associated with a higher risk of mortality . Ÿ Sepsis is said to effect the hypothalamic pituitary adrenal axis, causing a relative adrenal insufficiency resulting in cardiovascular instability,metabolic disorders,and a sustained pro- inammatory state. Ÿ The role of pro-inammatory pathways suggests a potential use for corticosteroids as an adjuvant therapy in the treatment of sepsis and septic shock .The Surviving Sepsis campaign guidelines recommend that if adequate uid resuscitation and vasopressors have not restored the hemodynamic stability,it was postulated in limited data to use inj hydrocortisone 100mg i/v 8 hourly for 7 days . Ÿ There was an improvement in the overall survival and reduction in the mortality and morbidity of patients, as observed by early weaning off from vasopressor support,reduction in total leucocyte counts

Relative adrenal insufficiency is a risk factor and endotype of sepsis - A proof-of-concept study to support a precision medicine approach to guide glucocorticoid therapy for sepsis.

25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether GC therapy should be based on the status of RAI are highly controversial. Our poor understanding about the pathogenesis of RAI and a lack of RAI animal model present significant barriers to address these critical issues. Scavenger receptor BI (SR-BI) regulates stress-induced GC (iGC) production in response to stress. We generated SF1CreSR-BIfl/fl mice and utilized the mice as a RAI model to elucidate the pathogenesis of RAI and GC therapy in sepsis. SF1CreSR-BIfl/fl mice did not express SR-BI in adrenal gland and lacked iGC production upon ACTH stimulation, thus, they are RAI. RAI mice were susceptible to cecal ligation and puncture (CLP)-induced sepsis (6.7% survival in SF1CreSR-BIfl/fl mice versus 86.4% in SR-BIfl/fl mice; p = 0.0001). Compared to a well-controlled systemic inflammatory response in SR-BIfl/fl mice, SF1CreSR-BIfl/fl mice featured a persistent hyperinflammatory response. Supplementation of a low stress dose of GC to SF1CreSR-BIfl/fl mice kept the inflammatory response under control and rescued the mice. However, SR-BIfl/fl mice receiving GC treatment exhibited significantly less survival compared to SR-BIfl/fl mice without GC treatment. In conclusions, we demonstrated that RAI is a risk factor for death in this mouse model of sepsis. We further demonstrated that RAI is an endotype of sepsis, which features persistent hyperinflammatory response. We found that GC treatment benefits mice with RAI but harms mice without RAI. Our study provides a proof of concept to support a precision medicine approach for sepsis therapy - selectively applying GC therapy for a subgroup of patients with RAI.

Relative adrenal insufficiency in the non-critically ill patient with cirrhosis: A systematic review and meta-analysis.

Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non-critically ill patients with cirrhosis. A systematic review and meta-analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid-MEDLINE, ScienceDirect, Web of Science, Cochrane Library and ClinicalTrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 μg/dl, delta total cortisol <9μg/dl or composite of the two thresholds in response either a standard-dose or low-dose short synacthen test. Odds ratios and standardized mean differences from random-effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. Twenty-two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33-42%). The prevalence of RAI varied by Child-Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety-day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69-4.92, I2=15%, p < 0.001). Relative adrenal insufficiency is highly prevalent in non-critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.

PMON123 Diagnostically Challenging Case of Cushing's Syndrome from a Pancreatic Neuroendocrine Tumor Treated with Radiofrequency Ablation

Abstract Background The delayed diagnosis of Cushing's syndrome (CS) results in advanced disease, treatment delays and poor outcomes. We present a patient with ectopic ACTH-syndrome (EAS) from a pancreatic neuroendocrine tumor (NET) whose care posed significant diagnostic and therapeutic challenges. Clinical Case 59F with classic Cushing's stigmata (including striae, plethora, supraclavicular and dorsocervical fat pads, muscle wasting), and two-year history of rapid weight gain, hypertension, T2DM, hyperlipidemia, severe osteoporosis complicated by multiple vertebral compression fractures, presented for workup and management of ACTH dependent CS. CS was confirmed (Baseline: ACTH 96 [7.2-63.3 pg/ml], serum cortisol 19.6 [4.8 - 19.5 mcg/dL]; LDSST: cortisol 18.5 [&amp;lt;1.8 mcg/dL], dexamethasone 547 [&amp;gt;200 ng/dL]; 24-hour Urine Free Cortisol: 191.60 [&amp;lt;45 mcg/d], 24-hour Cr 484 mg/day; LNSC: 436, 464 [29-101 ng/dL]; 8 mg ODST cortisol 7.2 mcg/dL). Pituitary MRI showed possible 0.5 cm left anterior pituitary lesion. Inferior petrosal sinus sampling (IPSS) to differentiate between Cushing's disease and EAS was initially planned, however, her course was complicated by an NSTEMI and acute/subacute lacunar infarcts in the left parietal and frontal lobes, and IPSS was deemed contraindicated. Additional workup was pursued including POMC 154 [&amp;lt;40 fmol/ml], Chromogranin A 538 [0-103 ng/ml] (on pantoprazole), pancreatic polypeptide 798 [0 - 435 pg/mL], 24-hour 5HIAA/Creatinine 3 [0 - 15 mg/24hr]. Chest/Abdominal/Pelvis CT showed a 1.5 cm incidental lipid rich adrenal adenoma; workup was negative for pheochromocytoma/ Conn's tumor/ adrenocortical carcinoma. Given elevated POMC and clinical suspicion for EAS, the patient underwent 68Ga-DOTATATE PET-CT scan which revealed an avid 7 mm lesion (SUVmax 14.5) in the pancreatic tail suspicious for a pancreatic NET- the presumed ectopic source of ACTH. Given the patient's poor functional status she was not a candidate for tumoral resection via distal pancreatectomy. Ketoconazole was initiated for treatment of hypercortisolism with good biochemical control, but the patient developed liver toxicity. The decision was made to pursue endoscopic ultrasound guided biopsy and radiofrequency ablation of the lesion. Pathology confirmed ACTH immunoreactive low-grade pancreatic NET. Post-procedure, morning ACTH was 8 pg/ml and cortisol was 9.1 mcg/dL, and the patient required steroids for relative adrenal insufficiency. Further follow up with repeat POMC, cortisol, ACTH levels, 24-hour UFC is required to monitor response. Conclusion IPSS is the gold standard test for differentiating Cushing's disease from EAS but is only available in select centers and for suitable candidates. This case supports the potential utility of POMC peptide measurements in the differential diagnosis of CS and the use of advanced nuclear imaging modalities for tumor localization. For patients with functional pNET who are poor surgical candidates or intolerant of pharmacotherapy, novel endoscopic ablation may offer a lower risk therapeutic option and its use should be further investigated. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

S1225 Relative Adrenal Insufficiency in Decompensated Cirrhosis: A Systematic Review and Meta-Analysis

S1225 Relative Adrenal Insufficiency in Decompensated Cirrhosis: A Systematic Review and Meta-Analysis