Background: Insulinoma is a rare functional pancreatic neuroendocrine tumour and the most common cause of endogenous hyperinsulinaemic hypoglycaemia in adults. Diagnosis is frequently delayed due to non-specific and intermittent symptoms, and a high index of suspicion is needed. Case description: We report the case of a 40-year-old non-diabetic woman who presented with recurrent episodes of weakness shortly after initiation of a glucagon-like peptide-1 receptor agonist (GLP-1RA). Laboratory evaluation demonstrated inappropriately elevated insulin and C-peptide levels during documented hypoglycaemic events, consistent with endogenous hyperinsulinaemia. Autoimmune and exogenous causes were excluded. Imaging studies identified a 2 cm hypervascular pancreatic lesion, with functional imaging confirming somatostatin receptor avidity consistent with an insulin-secreting tumour. The patient was initially treated with diazoxide as a bridge to definitive management. She subsequently underwent laparoscopic distal pancreatectomy, with histopathology confirming a well-differentiated pancreatic neuroendocrine tumour (WHO Grade 1). Following surgery, hypoglycaemia resolved completely. Conclusion: This case highlights the potential of GLP-1 receptor agonist therapy to unmask an insulinoma. Many benign insulinomas exhibit abundant expression of GLP-1 receptors. While a high index of suspicion remains essential, awareness of the emerging association between the incretin-based therapies and unexplained hypoglycaemia may facilitate earlier diagnosis.

BACKGROUND:Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF). OBJECTIVES:To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF). METHODS:We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i. RESULTS:Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury. CONCLUSIONS:In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

We report a case of severe symptomatic hypercalcemia that resolved after a short course of therapy of exclusively fluids and furosemide. An extensive workup for metabolic, neoplastic, and drug-induced causes did not provide a possible etiology of the hypercalcemia. After calcium level returned to baseline, the patient was discharged, only to return a week later with multiple embolic strokes of unknown source. The comparison of cardiac imaging obtained during the hospitalization periods established a possible mechanism for both phenomena; the interior caseous cavity of a calcified mitral annulus (CMAC), which was demonstrated on echocardiography during the first hospitalization, disappeared in a subsequent study in the second hospitalization, probably reflecting a fistulization of the structure into the left ventricle. The spill of contents into the bloodstream, over several days presumably, explains the transient increase in calcium, and the embolic events that followed. We hereby demonstrate a clear relationship between the fistulization of a CMAC and hypercalcemia, emphasizing the risks of this valvular pathology, and introducing a rare mechanism for transient and potentially severe hypercalcemia.

Abstract Disclosure: Y. Sofer: None. E. Osher: None. Y. Greenman: None. K.M. Tordjman: None. G. Shenkerman: None. M. Yaron: None. Y. Marcus-Perlman: None. Y. Moshe: None. S. Shaklai: None. R. Limor: None. S. abiri: None. D. Cantrell: None. N. Stern: None. Objective: Some clinical resemblance may exist between obesity, particularly abdominal obesity, and Cushing’s syndrome. This has stimulated ongoing interest in the role of cortisol's secretion pattern, control and metabolism in obesity. Goals: To compare basal and dynamic cortisol response to an intravenous bolus dose of 1 ug ACTH in healthy obese versus lean controlsDesign: Total, free and salivary cortisol were tested at the basal state and after a standard challenge with 1 ug ACTH in 60 healthy obese subjects (mean BMI= 39 kg/m2) and 54 healthy lean controls (mean BMI=23 kg/m2). Results: Basal total cortisol was significantly lower in obese as compared to lean subjects [361.56+/-132 vs 414+/- 121 nmol/L; p=0.019]. Additionally, baseline total cortisol and salivary cortisol were inversely related to BMI (r=-0.24, r=-0.27; p<0.05 for both). Baseline total and salivery cortisol were also negatively correlated with waist circumference (r=-0.27, r= -0.34; p<0.05 for both). Upon challenge with ACTH, total and salivary cortisol response were significantly lower in obese than in lean subjects [665.16+/-151.8 vs. 728.64+/- 124.2 nmol/L, p<0.05; 31.66 (19-38.64) vs. 40.05 (31.46-46.64) nmol/L, p<0.05]. Conclusion: Basal as well as peak stimulated cortisol and integrated post-1ug ACTH-stimulated total serum cortisol levels were significantly lower in obese subjects. Obesity is not associated with enhanced basal cortisol or ACTH-stimulated cortisol reserve. Hence, increased serum or salivary cortisol is atypical for uncomplicated obesity. Presentation: 6/1/2024

Endotoxemia commonly occurs in severe and fatal COVID‐19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS‐CoV‐2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP‐1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram‐negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID‐19 severity with endogenous GLP‐1 activation upregulated by increased specific pro‐inflammatory innate immune response in patients with and without T2D.

Abstract Background There is recent concern regarding the documented mismatch between demand and supply, vis-à-vis the growing need for trained endocrinologists unmet by parallel rise in the world workforce of endocrinologist. Due to the increasing complexity of disease in inpatients, in recent years we have experienced a growing demand for inpatient endocrine consults. Surprisingly, the need for the endocrinology subspecialty in the overall care of inpatients in the current setting of general hospitals has received little attention. Methods A retrospective analysis of endocrine consult service based on solicited consults carried out during 3 consecutive months. Results During 3 months, there were 767 consults, comprised of 156 diabetes referrals and 611 endocrine/metabolic consult requests. The 611 "non-glucocentric" consult requests were related to 295 inpatients (2.1 ± 2.7 consults/patient). Mean patient age was 58.9 ± .18 years (range 21–92), with some F/M preponderance (58/42%). Requests for endocrine consults were evenly distributed (49.8%, 50.2%) between internal medicine and surgery wards. Case distribution was as follows: thyroid 45.4%, calcium & bone 11.5%, pituitary 12%, adrenal 10% and all others 8.1–0.7%. The mean response time was 4.4 ± 2.7 h. The consults had a discernible effect on the patients' disease management in 60% of the patients. Of these, the consults modified the hospital treatment in 74%, the discharge treatment recommendations in 19% and the diagnosis in 7%. Conclusion At a large medical center, endocrine consults were requested for ~ 3.3% of all admitted inpatients. The endocrine consults modified pre-consult diagnosis or treatment in ~ 60% of the cases. Contrary to its common image as an exclusively outpatient-based subspecialty, endocrinology practiced by specialists and endocrine trainees has a notable role in the daily care of inpatients admitted to a referral general hospital.

Abstract Aims: Assessment of psychosocial stress remains a major obstacle in understanding its association with diabetes. We examined the validity of methods used to measure psychosocial stress in relation to diabetes incidence and control. Methods: 125 studies of psychosocial stress and diabetes published between 1983 and 2017 were evaluated. Evaluation included the stress type definition, study’s design, methodology of stress assessment and diabetes outcomes (incidence and/or control).Results: An association between stress and diabetes outcomes was found in 89% of studies. Prospective designs were commonly employed (38%), followed by cross-section designs (18%). More studies (64%) focused on psychosocial stress than sleep disorder related stress (22%). More studies explored diabetes incidence as an outcome (74%) than diabetes control (22%). The most common measure for stress assessment was a self-administered questionnaire (64%), followed by physiological indicators (7%). An analysis of the validity of the measures used, indicates that 67% of the studies used valid measures, with self-administered questionnaires exhibited a similar validity as other tools. Interestingly, the validity of tools used to evaluate sleep disorders severity was generally higher than those used to evaluate psychosocial stress.Conclusion: The majority of studies evaluating the association between anteceding stress and diabetes outcome applied valid measures.

BACKGROUND Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series.

Introduction We examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up. Research design and methods Men and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976–1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied. Results At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m 2 , at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia. Conclusions This study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.

Background and aims: Glucagon Like Peptide-1 Receptor (GLP-1R) activation reduces pro-inflammatory responses of human monocytes, their accumulation in the vascular wall and foam cell formation inhibiting atherosclerogenesis. This suggests that reduction of circulating GLP-1-1R positive monocytes may have pro-atherogenic effects. It is unknown whether different CD14/CD16 monocytes subsets display GLP-1R and whether their relative proportions correlate with atherosclerosis severity. We evaluated the association between GLP-1R positivity in different CD14/CD16 monocyte subsets and coronary atherosclerosis severity. Methods: Relative amounts of classical (CD14+/CD16-), intermediate pro-inflammatory (CD14+/CD16+) and non-classical patrolling (CD14-/CD16+) subsets of total circulating monocytes and the proportions of GLP-1R positive monocytes in these subsets were determined in 13 control subjects and 10 dyslipidemic ischemic heart disease (IHD) patients with severe angiographic proven coronary atherosclerosis using flow cytometry analysis. Atherosclerosis severity was calculated by SYNTAX score. Results: In univariable analysis, severe atherosclerosis was associated with decreased proportion of classical monocytes and two fold increased CD16+ pro-inflammatory and patrolling subsets as compared with controls (p = 0.01, p = 0.02 and p = 0.01, respectively). Frequency of GLP-1R positive monocytes was decreased in both CD16+ subsets (p = 0.02 and p = 0.05, respectively) and negatively correlated with atherosclerosis severity (r = -0.65, p = 0.005 and r = -0.44, p = 0.05, respectively). Conclusions: Increased skewing of the classical monocyte population toward CD16+ pro-inflammatory and patrolling subsets accompanied by decreased in GLP-1R positivity are associated with coronary atherosclerosis severity in IHD patients with dyslipidemia. Although the effect of potential confounders cannot be ruled out, our data suggest that failure of GLP-1R-dependent anti-inflammatory/anti-atherogenic control results in innate immune system dysfunction and can promote atherosclerogenesis. (c) 2021 The Authors. Published by Elsevier B.V.

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

Background: The prevalence of prediabetes is gradually increasing and its association with life years lost (LYL) is yet to be determined. Objective: to examine LYL associated with prediabetes as compared to normoglycemia, by age, sex, country of origin, smoking status, BMI, and blood pressure, using data of the Israel Study of Glucose Intolerance, Obesity and Hypertension (GOH) 40-year follow-up. Methods: The population of the current study included 2,844 men and women (mean age 52±8.2 years) who underwent OGTT and anthropometric measurements, during 1976-1982, and were followed for mortality until May 2019. Normoglycemia, Prediabetes and diabetes were defined according to fasting plasma glucose, 2-hour post OGTT plasma glucose, reporting of having diabetes or use of antidiabetes medications. By the end of follow-up 27.7% remained alive and multiple imputation procedures were used for missing mortality dates. Results: At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, prediabetes, and diabetes, respectively. Using multiple regression mixed models, the average difference in LYL associated with prediabetes as compared to normoglycemia was 4.3 years (95%CI 3.3-5.2; p<0.001). LYL were higher in prediabetic women than in prediabetic men 4.4 (95%CI 3.0-5.7) vs. 3.3 (95%CI 1.9-4.8). These differences persisted mainly in individuals younger than 60 years, with BMI<25 kg/m2, never smokers, and normotensives at baseline. Significant reductions of 9.9 years (95%CI 8.6-11.2) were observed for diabetes as compared to prediabetes and 14.2 years on average (95%CI 12.8-15.5) as compared to normoglycemic individuals. Conclusions: This study reveals that life expectancy of middle-aged individuals with prediabetes is more than 4 years shorter than of normoglycemic individuals. As expected, diabetes was associated with the greatest LYL in this long-term cohort study. Disclosure M. Rapoport: None. A. Chetrit: None. I. Novikov: None. D. Cantrell: None. R. Dankner: None.

Objective: While osteoporotic fractures are reported in up to 40% of adults with post-poliomyelitis syndrome (PPS), clinical guidelines regarding bone mineral density (BMD) and indications for treatment are scarce. We investigated the characteristics of PPS patients, focusing on fractures and osteoporosis as the primary outcomes. Methods: A cross-sectional retrospective data analysis from medical records of 204 PPS patients regarding their clinical characteristics and long-term outcome, with emphasis on bone metabolism status. Results: Our cohort included 53% women, mean age was 65 years at study entry, and 1.7 years at the diagnosis of acute poliomyelitis. The lower limb was involved in 97.5% of patients, and the BMD in the affected limb tended to be lower than the unaffected, with a T score (Tsc) of -1.64 vs. -1.19, respectively (p=0.06). Recurrent falls were documented in 39.2% of patients, and osteoporosis in 20.6%, being more frequent in women (p=0.003) and patients with fractures (p=0.002). At least one fracture occurred in 52.2% of patients, and more than one in 40.3%. The median age for the first fracture was 57.5 years (range 30-83), and most fractures occurred in the affected limb (73.2%). Conclusion: Underdiagnosis and delayed treatment of osteoporosis in late-adulthood post-poliomyelitis patients underlie the need for comprehensive clinical guidelines to manage these patients, including recommendations on bone health assessment, medical treatment, and their inclusion as a high-risk group for bone fractures.

BACKGROUND Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown. OBJECTIVES To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment. METHODS Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined. RESULTS Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found. CONCLUSIONS Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

OBJECTIVE Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. METHODS Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. RESULTS The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI ( P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. CONCLUSION Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines. ABBREVIATIONS ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin.

Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear–nose–throat (ENT) surgeons and endocrinologists.

BACKGROUND Facing the prevailing concept that increased diagnosis with no change in mortality drives the increased incidence of differentiated thyroid cancer (DTC), considerable modifications have been introduced in the new edition of the tumor node metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to compare a group of DTC patients before and after restaging, by mortality, disease severity, and disease outcomes. METHODS DTC patients (N = 433) were restaged according to the eighth TNM/AJCC edition, and the results were compared to the seventh edition for clinicopathologic data, treatment modalities, and disease outcomes. RESULTS When switched to the eighth edition, 97.5% of patients fell into stage I-II compared to 76.4% before, and only 11/102 patients remained in stages III-IV. Disease-specific mortality was recorded in 11/433 patients, six of whom were in stages I-II upon restaging, compared to none before (p > 0.05). In addition, more recurrences were seen in stages II (p = 0.05) and III (p = 0.03) using the eighth edition compared to the seventh edition. Stage II was affected the most, with recurrence risk increasing from 29% to 76% (p = 0.001) and persistence at last visit from 19% to 43% when switching to the eighth edition (p = 0.01). Considering stages I and II together, the recurrence risk increased from 16.7% to 28.2% (p = 0.01), lymph node metastases from 1.9% to 26.5% (p = 0.01), and persistence at last visit from 10% to 15% (p > 0.05). Of the 129 patients in the 45- to 54-year-old age group, 53 shifted to stage I (20 from stage II, 29 from stage III, and 4 from stage IV) and five shifted to stage II (all from stage IV). When comparing this age group in stage II only, the eighth edition showed more lymph node metastases (p = 0.001), more distant metastases (p = 0.003), higher recurrence risk (p = 0.002), and more persistence at the last visit (p > 0.05). CONCLUSION The eighth TNM/AJCC edition provides a more accurate system to discriminate mortality and persistence in DTC patients. Yet, the severity of disease, especially in the 45- to 55-year-old age group and in stage II patients, should not be underestimated following the downstaging of these patients.

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

T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R) expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO) by high-energy (HE) diet and by streptozotocin (STZ) in Sprague Dawly (SD) rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.