Endogenous Hyperinsulinism Research Articles

7940 Insulinoma as a Rare Manifestation of MEN4

Abstract Disclosure: H. Han: None. J. Moalem: None. A.R. Shih: None. B.J. Gigliotti: None. Background/Objective: Multiple endocrine neoplasia 4 (MEN4) is a rare syndrome that is caused by germline mutations in CKDN1B. Its phenotypic expression is similar to multiple endocrine neoplasia 1 (MEN1). Manifestations include primary hyperparathyroidism (PHPT), pituitary adenomas, and pancreatic neuroendocrine tumors (NET). Prevalence of MEN4 is less than one per million. Case Report: A 55-year-old female with history of hypercalcemia presented with symptomatic hypoglycemia. She had a fasting plasma glucose of 41mg/dL, proinsulin of 84.3 pmol/L, insulin level of 24 uIU/mL, c-peptide of 5.2 ng/mL, and beta hydroxybutyrate level of 0.34 mmol/L, consistent with endogenous hyperinsulinism. She was incidentally noted to have PHPT. CT abdomen showed a 1.5 x 1.1 x 1.0 cm pancreatic lesion consistent with an insulinoma. Pathology from subsequent Whipple surgery showed that it was a well-differentiated neuroendocrine tumor with no metastasis. She became normoglycemic after surgery. Germline testing revealed a variant of unknown significance in CDKN1B (p.R93W). Discussion: Increasing evidence suggests that MEN4 exhibits subtle differences in penetrance and natural history compared to MEN1. A recent systemic review of MEN4 cases showed that most gastrointestinal NETs in MEN4 are non-functional NETs and gastrinomas; to date, no insulinomas have been reported. PHPT in MEN4 may exhibit a lower risk of recurrence after parathyroidectomy. This case highlights the importance of germline genetic testing when a patient presents with clinical manifestations of MEN1. Conclusion: This is the first reported case of insulinoma in MEN4. Presentation: 6/3/2024

9337 Postprandial And “Fasting” Hypoglycemia In A Patient With A History Of Gastric Bypass Surgery And Carcinoid Syndrome

Abstract Disclosure: S. Ntelis: None. M. Pennant: None. Background: Hypoglycemia is an increasingly recognized complication of bariatric surgery that can occur years after the procedure. Episodes most commonly occur 1-3 hours after meals. Fasting hypoglycemia is not typical and raises concerns for other etiologies, including adrenal insufficiency and other causes of endogenous hyperinsulinism. Clinical Case: A 51-year-old woman with a history of carcinoid tumor of unknown origin with liver metastases, treated with monthly octreotide injections, and history of Roux-en-Y gastric bypass presented with multiple episodes of symptomatic hypoglycemia up to 24 mg/dl. Symptoms included tremor and diaphoresis and improved with juice. Morning cortisol was 22.7 mcg/dL (n > 19.4 mc/dL), ruling out adrenal insufficiency. A continuous glucose monitor (CGM) was placed, and she was advised to have frequent low-carbohydrate meals mixed with healthy fats and protein. She was also advised to add cornstarch to meals, until mixed-meal testing could be performed. She was hospitalized for a seizure provoked by hypoglycemia after a heavy high-carbohydrate meal, and treatment with acarbose 25 mg three times daily was started. Mixed-meal testing was consistent with post-prandial hyper-insulinemic hypoglycemia, with elevated insulin (58 mcIU/ml, n: 2.6-24.9 mcIU/ml) and c-peptide (11.2 ng/ml, n: 1.1-4.4 ng/ml) levels during an episode of symptomatic hypoglycemia (glucose 22 mg/dL) 2.5 hours after the patient’s meal. CGM showed hypoglycemia mostly occurring after meals and some episodes of hypoglycemia early in the morning, that occurred after late-night snacks. Clinical picture and laboratory testing were suggestive of post-bariatric surgery hypoglycemia. Poor hepatic glycogen reserve, secondary to the liver metastases, was considered a contributing factor. Interestingly, although hypoglycemia was mediated by hyperinsulinemia, treatment with a somatostatin analogue provided no benefit. The frequency of hypoglycemia decreased with adherence to a low-carbohydrate diet, and episodes mostly occurred when acarbose use was delayed. Octreotide was transitioned to lantreotide. Due to persistence of early-morning low glucose values on follow-up, further work-up was pursued to rule out etiologies of fasting hypoglycemia. Glucose values remained >70 mg/dl during 72 hours of fasting. IGF-I (115 ng/ml, n: 53-287 ng/ml) and IGF-II (608 ng/ml, n: 267-616 ng/ml) levels were normal, and insulin antibodies were undetectable. Post-bariatric surgery hypoglycemia was confirmed and acarbose dose was increased to 50 mg three times daily. Conclusion: Postprandial hypoglycemia is a late complication of bariatric surgery. Early-morning hypoglycemia can also be seen after bariatric surgery in patients who have late-night meals and snacks. Presentation: 6/1/2024

Insulinoma in Patients with Diabetes- A Systematic Review of Previously Reported Cases

Abstract Introduction: Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes. Methods: We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: ‘insulinoma’, ‘diabetes’, ‘nesidioblastosis’, ‘endogenous hyperinsulinism’, ‘hypoglycaemia’, and ‘hyperglycaemia’ (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods. Results: Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17–96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%–8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis. Conclusion: This first systematic review provides insights into the uniqueness of insulinoma in diabetes.

Инсулинома: обзор литературы и описание клинического наблюдения

Insulinoma is a neuroendocrine tumor arising from β-cells of the islets of Langerhans, causing hypoglycemic attacks due to endogenous hyperinsulinism. The worldwide prevalence is approximately 1 case per 250,000–1,000,000 population, the incidence is 1–4 cases per million population per year. In most cases, the formation of insulinoma is sporadic (90%), less often it can be detected as part of the multiple endocrine neoplasia syndrome type 1 (10%). This review discusses the pathogenetic mechanisms of hypoglycemic syndrome, criteria for differential diagnosis, modern laboratory and imaging methods, and approaches to the treatment of insulinoma. A clinical observation is presented that demonstrates the difficulties of timely diagnosis of insulinoma due to nonspecific manifestations of hypoglycemia. The time that elapses from the first manifestations of hypoglycemic syndrome to diagnosis directly affects the prognosis and quality of life of a patient with insulinoma. It requires vigilance from doctors of all specialties regarding the clinical features of this disease.

Non-diabetic hypoglycemia

Glucose is the main substrate utilized by the brain, and therefore numerous counterregulatory mechanisms exist to maintain plasma glucose concentration. This makes it rare for hypoglycemia to develop in people who are not taking hypoglycemic drugs, such as insulin or sulfonylureas, for diabetes. The symptoms of hypoglycemia are nonspecific. The presence of Whipple’s triad is necessary for diagnosis. When symptoms occur spontaneously, the patient can be evaluated for hypoglycemia. If this is not possible, then a 72-hour fasting test or a mixed meal tolerance test can be performed to create conditions for symptoms to occur. Non-diabetic hypoglycemia is mainly divided into two main groups: insulin-mediated (hyperinsulinism) and insulin-independent. The main causes of hypoglycemia due to endogenous hyperinsulinism are insulinoma and islet cell hyperplasia (nesidioblastosis), post-bariatric surgery, and autoimmune hypoglycemia with the presence of anti-insulin antibodies. Other important causes of hypoglycemia include hypoglycemic drugs, non-islet cell tumors, hormonal deficiencies (primary adrenal insufficiency, anterior pituitary insufficiency), and critical illnesses (liver/kidney failure). In this article, we provide an overview of the pathogenesis and treatment of hypoglycemia.

Clopidogrel-induced non-diabetic hypoglycemia reported from Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a case report

BackgroundRecurrent episodes of hypoglycemia may be caused by several factors, including drugs, critical illnesses, hormonal deficiency, non-islet cell tumor endogenous hyperinsulinism, and accidental, surreptitious, or malicious hypoglycemia. Multiple drugs have been previously reported as causes of hypoglycemia, with moderate and low-quality evidence. However, Clopidogrel as a cause of non-diabetic hypoglycemia is rarely reported. Here we describe a single non-diabetic patient who experienced recurrent episodes of hypoglycemia after initiation of clopidogrel for clinical suspicion of acute coronary syndrome.Case presentationThe patient, a 33-year-old Ethiopian male with documented hypertension on antihypertensive medication, has started receiving treatment for acute coronary syndrome after experiencing angina symptoms. He experienced hypoglycemia following the start of Clopidogrel, but it subsided once it was stopped. Currently, he has a follow-up at the cardiac clinic with a normal measurement of his serum blood glucose level.ConclusionNon-diabetic hypoglycemia is a rare illness characterized by low blood glucose levels in people who do not have diabetes. Patients with severe hypoglycemia may become unconscious or have seizures as a result of low blood sugar. Severe hypoglycemia is fatal and must be treated as soon as possible. Therefore, if non-diabetic hypoglycemia occurs, a thorough evaluation of the causes is essential, particularly any potential drug as a cause of hypoglycemia should be evaluated.

FRI665 Hirata's Syndrome: Autoimmune Hypoglycemia Diagnostic Pathway, A Mexican Case Report

Abstract Disclosure: G. Gonzalez De La Cruz: None. D. Porras Farret: None. Introduction: Autoimmune hypoglycemia or Hirata syndrome is a very rare cause of hypoglycemia in western populations, as an example, in Mexico until 2015, there was only a single case reported with these characteristics. Diagnosis is based on episodes of spontaneous, fasting or postprandial hypoglycemia, with endogenous hyperinsulinism, without pancreatic lesions on imaging and positive tests. Objective: To describe the approach to a patient with hypoglycemia, specifically to those with characteristics of autoimmune hypoglycemia syndrome, as well as the general approach to hypoglycemia of endogenous origin and the differential approach in those with a history of type 2 diabetes or drug use with secondary effects. Case description: An 86-year-old woman with a history of high blood pressure, prediabetes, and osteoporosis, presented episodes of dizziness, palpitations, diaphoresis, and syncope, documenting plasma glucose of 40 mg/dl. She was attended by paramedics responding adequately to oral glucose. She was evaluated by Cardiology, Holter was performed with predominant sinus rhythm, frequent atrial extrasystoles (2%) and infrequent ventricular extrasystoles. Next, she was referred to Endocrinology for evaluation and treatment, she was taken empagliflozin as prediabetes medication, and it was suspender. Laboratory studies are requested to address hypoglycemia, with serum insulin levels greater than 600 mU/l, c-peptide 3.9 ng/ml, TSH 6.1, T4T 7.5, T3T 67.8, T4L 1.1, ALT 26 U/L, AST 18 U/L, DHL 247 U/L, GGT 26 U/L, Cortisol 13.8 mcg/dl. An MRI of the upper abdomen was performed where there is no evidence of pancreatic injury. A profile of serum hypoglycemic agents (sulfonylureas in blood) was requested, which were not detected. Subsequently, anti-insulin studies were requested, which were reported in amounts greater than 100 U/ml. The diagnosis of autoimmune hypoglycemia syndrome was made, starting management with prednisone 70 mg every 24 hours, in addition to dietary changes. Conclusion: The approach to hypoglycemia in patients without clear evidence of exogenous administration of hypoglycemic agents must be ordered, taking into account differential diagnoses such as autoimmune causes. In the case of autoimmune hypoglycemia, remission is expected at 6 months, with constant monitoring and adjustment of drugs for underlying pathologies. Presentation: Friday, June 16, 2023

THU391 A Case Of Unrecognized Hypoglycemia Due To Methadone Use In A Non-Diabetes Patient

Abstract Disclosure: D. Owais: None. J.R. Fredrick: None. Y. Jamal: None. S. Sajnani: None. Introduction: Methadone is a rare cause of insulin-mediated hypoglycemia. Hypoglycemia can be manifested as autonomic instability (palpitations and diaphoresis) and neuroglycopenia (agitation and altered mentation). We present the case of hypoglycemia in a non-diabetic patient with no renal insufficiency and who was on a high dose of Methadone. Case: A 76-year-old male with a medical history of HTN, CAD, CVA, dementia, chronic opioid use (on methadone 80 mg) initially presented two times to an outside hospital for intractable seizures. The diagnosis of seizure disorder was made and was discharged on valproate. Per his wife, he had a few low blood sugars during those hospitalizations. Within a month of discharge, he was admitted to another hospital for severe bradycardia and had undergone pacemaker implantation. He was then discharged to nursing home (NH). In the NH, the routine laboratory work showed a serum blood glucose of 42; however, it was interpreted as a lab error. The next day, he developed severe metabolic encephalopathy, intractable seizures and transferred to our hospital. On arrival, serum blood sugar was 59, corrected by 50% of dextrose. His physical examination was significant for a thin-built elderly male, lethargic but in no acute distress. The dose of antiseizure medication was adjusted. The Methadone 80 mg daily was resumed. He continued to have intermittent hypoglycemia to as low as 33 despite being on intravenous (IV) dextrose solutions. His symptoms used to improve temporarily after the correction of hypoglycemia. (Positive Whipple’s triad). Blood cultures and urine cultures were negative. Serum cortisol level, IGF -1, TSH levels, blood pressure, and electrolytes were within normal limits. The hypoglycemia workup performed in a fasting state (off IV dextrose) showed endogenous hyperinsulinism with insulin level >3, C-peptide level >0.2, beta-hydroxybutyrate level of <2.7, and negative sulfonylurea screen. CT scan and ultrasound of the abdomen were performed to rule out insulinoma; however, it demonstrated complete atrophy of the pancreas. Therefore, a high dose of methadone was assumed to cause hypoglycemia, as the patient had no hypoglycemic episodes when he could not receive two doses of methadone due to encephalopathy. The trough levels of methadone in the blood were high at 650 ng/dl. Methadone dose was tapered to 60 mg daily. He was also started on octreotide to manage his hypoglycemia. However, the patient developed severe pneumonia, and family opted for hospice. Conclusion: Our case is unique as the patient was developing severe signs of hypoglycemia, including bradycardia and seizures, and treated with a pacemaker and antiseizure medications. His Methadone-induced hypoglycemia was identified late as the cause of his symptoms. Therefore, it is crucial to recognize this side effect of Methadone in differentials in a patient with hypoglycemia. Presentation: Thursday, June 15, 2023

Insulinoma in a thin Lean Indian male

Insulinoma is a tumor that secretes insulin, leading to hypoglycemia as a result of excessive insulin release. The diagnosis of insulinoma is based on the presence of Whipple’s triad, which includes the following criteria: symptoms of hypoglycemia such as tremor, sweating, irritability, uneasiness, and weakness; a plasma glucose concentration of less than 55 mg/dL (3.0 mmol/L); and resolution of symptoms upon administration of glucose. A 30-year-old male presented with recurrent episodes of palpitations, sweating, dizziness, and vision difficulty, primarily occurring in a fasting state and relieved by food ingestion. Investigations revealed hypoglycemia during an episode, along with endogenous hyperinsulinism. Imaging studies showed a hyperenhancing lesion in the pancreatic body, which was confirmed as a neuroendocrine tumor on histology and immunohistochemistry. The patient underwent enucleation of the lesion, resulting in the normalization of plasma glucose levels postoperatively.

Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia.

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.

C-peptide level concomitant with hypoglycemia gives better performances than insulin for the diagnosis of endogenous hyperinsulinism: a monocentric study of 159 fasting trials

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

C-peptide level concomitant with hypoglycemia gives better performances than insulin for the diagnosis of endogenous hyperinsulinism: a single-center study of 159 fasting trials.

Diagnosis of endogenous hyperinsulinism relies on the occurrence of a hypoglycemia, concomitant with inadequate high insulin and C-peptide levels. However, diagnostic cutoffs are not consensual among the different learned societies. The objective of this work was to propose optimized cutoffs for these three parameters for the diagnosis of endogenous hyperinsulinism. All the patients having performed a fasting trial in Cochin Hospital Endocrinology Department between February 2012 and August 2022 were included. The results of glycemia, insulin and C-peptide levels during fasting trial were collected and analyzed. One hundred and fifty-nine patients were included: 26 with endogenous hyperinsulinism and 133 without endogenous hyperinsulinism. ROC analysis of glycemia nadir during fasting trial identified the value of 2.3 mmol/L as the optimal cutoff, ensuring a sensitivity of 100% associated with a specificity of 81%. ROC analysis of insulin and C-peptide levels concomitant with hypoglycemia <2.3 mmol/L showed very good diagnostic performances of both parameters with respective cutoffs of 3.1 mUI/L (=21.5 pmol/L; sensitivity = 96%; specificity = 92%) and 0.30 nmol/L (sensitivity = 96%; specificity = 100%). Insulin to glycemia ratio as well as C-peptide to glycemia ratio (in pmol/mmol) at the time of glycemia nadir did not show better diagnostic performances than C-peptide alone. A C-peptide level 0.3 nmol/L concomitant with a hypoglycemia <2.3 mmol/L appears as the best criterion to make the diagnosis of endogenous hyperinsulinism. Insulin level can be underestimated on hemolyzed blood samples, frequently observed in fasting trial, and thus shows lower diagnostic performances.

Hypoglycemia In Non-Diabetic Patient: Report of Two Cases of Insulinoma

Background: Insulinoma is a B-cell tumor of the islets of the pancreas with an incidence of 4 per 1 million people per year, which produces excess insulin and can cause symptoms related to hypoglycemia at the level of the central nervous system or symptoms related to excess release of catecholamines. The presence of hypoglycemia, elevated insulin, proinsulin, and c-peptide levels suggest endogenous hyperinsulinism, which together with imaging findings suggestive of neuroendocrine tumor, allow establishing the diagnostic impression of Insulinoma. Case Report: Patients with neuroglycopenic symptoms, biochemical profile of hypoglycemia, endogenous hyperinsulinemia and radiological finding compatible with insulinoma are reported, who were treated by surgical resection of the tumor, with complete resolution of the initial symptoms. Conclusion: The clinical presentation, diagnosis and treatment of insulinoma represents a clinical challenge, since it is a rare pathology and the delay in diagnosis can have catastrophic consequences for the patient such as permanent brain damage and death.

Insulinoma - The Approach to the Diagnosis, Based on a Case Report

Insulinoma is the most common cause of endogenous hyperinsulinism. Most are benign and solitary. Hereby the authors present a 36-year-old woman who was admitted for confusion, aggressive behaviour, and visual hallucinations. Initial investigation revealed hypoglycaemia, and the patient recovered after the administration of intravenous glucose. The 72-hour fasting test was compatible with hyperinsulinism. Endoscopic ultrasound detected a nodule in the tail of the pancreas. Surgical resection of the nodule was performed, and histological examination revealed a pancreatic neuroendocrine tumour. The patient had a favourable outcome with resolution of the symptoms.

ODP626 Weekend Hypoglycemia: A Case of Intermittent Endogenous Hyperinsulinemic Hypoglycemia Caused by Prolonged Interval Between Hemodialysis Sessions in ESRD

Abstract Background Hypoglycemia is a common clinical dilemma with burden of risk to life, bothersome symptoms and expensive workup. With many different causes for hypoglycemia, initial workup includes differentiating insulin-dependent versus non-insulin dependent causes. Elevated insulin levels correlated with a C-peptide level can separate endogenous versus exogenous hyperinsulinemic hypoglycemia. If endogenous hyperinsulinism is discovered, further investigation into a wide array of pathology is warranted. We highlight a case of hyperinsulinemic hypoglycemia in a patient with end-stage renal disease on hemodialysis. Given limited treatment options, this case illustrates the importance of patient specific behavioral modifications. Case A 43-year-old man with T2DM with ESRD on hemodialysis (MWF) presents with recurrent episodes of severe hypoglycemia with altered mental status. On admission, serum glucose was 29 mg/dL and patient was treated with IV dextrose with resolution of symptoms. Patient denied taking anti-hyperglycemic medications. Patient was recently and similarly admitted two weeks prior where his insulin regimen (patient confirmed compliance) was discontinued due to severe hypoglycemia. Serum insulin and C-peptide at the time of this admission were 93.8 mg/dLand 29.57 nmol/L respectively. Insulin antibodies were negative. Although both values indicate an endogenous source for hyperinsulinemia, exact interpretation is unclear given his ESRD. Patient underwent hemodialysis on hospital day one. On hospital day two, patient's labs indicated hyperinsulinemic hypoglycemia again, with glucose of 56 mg/dL and an insulin of 24 mg/dL. Subsequently, an abdominal CT scan with triple phase washout was negative for an intra-pancreatic process. He had normal thyroid function, and history of adrenal insufficiency which was stable on maintenance doses of glucocorticoids. Patient also confirmed good appetite, stable weight, and albumin levels were appropriate. On hospital day 3, patient underwent his normally scheduled dialysis. Both pre- and post-dialysis insulin and C-peptide levels were collected, and insulin levels decreased &amp;gt;50% following dialysis. Patient was also started on diazoxide to reduce endogenous hyperinsulinemia after this session. No further hypoglycemia occurred during hospital stay. He was subsequently discharged home on hospital day 4 and educated on the increased likelihood of hypoglycemia during extended periods of time without dialysis, which in his case was weekends. In order to address this, he was instructed to have small, frequent mixed macronutrient meals and snacks on Sundays, leading up to Monday's dialysis session. Conclusion This case of "weekend hypoglycemia" highlights a perplexing presentation in a patient with ESRD on HD, of hyperinsulinemic hypoglycemia occurring only during prolonged interval (&amp;gt;2 days) between hemodialysis sessions. This is postulated secondary to a combination of ESRD with associated impaired renal clearance of insulin and impaired renal gluconeogenesis and resultant hyperinsulinemia that improved with dialysis sessions. Patient education on compliance with dialysis sessions and dietary counseling to reduce risk of hypoglycemia is key in management. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP215 Insulinoma Evaluation Before and After Development of End Stage Renal Failure: A Case Report

Abstract Introduction Fasting hypoglycemia in chronically ill patients with kidney disease is frequently multifactorial. Patients with chronic kidney disease are prone to hypoglycemia due to decreased renal clearance of insulin, impaired renal gluconeogenesis and increased prevalence of other medical problems and medications. However, ruling out the presence of an insulinoma can be difficult in this patient population due to the impact of kidney disease on laboratory evaluation of hypoglycemia. Case A 43-year-old male with history of paraplegia from gunshot wound, neurogenic bladder, colostomy, chronic osteomyelitis, frequent polymicrobial bacteremia was noted to have persistent, asymptomatic hypoglycemia during multiple inpatient hospitalizations dating back to 2007. He was taking no medications associated with hypoglycemia. Following normal ACTH stimulation and thyroid testing, he underwent a 72-hour fast in 2017 when his creatinine was 1.32 mg/dL and GFR was &amp;gt;60; BMI was 22.32 kg/m 2 with prealbumin of 15 mg/dL. The fast was concluded after 23.5 hours with serum glucose of 46 mg/dL, insulin level of 3.1 uIU/mL, c-peptide of 2.4 ng/mL, undetectable proinsulin, and beta-hydroxybutyrate of 0.62mmol/L and a negative sulfonylurea screen. Administration of glucagon at time of fast completion improved glucose to 65 mg/dL. He was started on diazoxide 85mg every 8 hours during that hospitalization, which he discontinued without medical recommendation in 2018. He developed end stage renal disease requiring hemodialysis in 2019. During an admission in 2020, serum fasting glucose as low as 30mg/dL. Further laboratory evaluation at that time revealed glucose of 47 mg/dL, with insulin level 39.1 uIU/mL, c-peptide 18.2 ng/mL, and proinsulin of 20.1 pmol/L. Multiple CT abdomen imaging studies confirmed normal pancreas. Diazoxide 110mg every 8 hours was resumed and patient had decreased frequency of hypoglycemia episodes. Diazoxide has since the tapered to 80mg twice daily without increase in hypoglycemia frequency, with goal to taper further in the future. Conclusion Here we present the case of an individual patient who underwent laboratory evaluation of hypoglycemia before and after development of end stage renal disease with profound differences in lab results despite similar degree of hypoglycemia. It has been demonstrated previously that c-peptide and insulin levels are elevated in patients with end stage renal disease and that these labs decrease with hemodialysis while remaining above normal range. The elevation of c-peptide in this population is thought to be due to the kidney being the main site of beta-cell polypeptide degradation. Additionally, this case suggests successful use of diazoxide therapy in patients without classic endogenous hyperinsulinism. Presentation: No date and time listed

Comparison Between Sporadic and Multiple Endocrine Neoplasia Type 1-Associated Insulinoma.

The differences between sporadic and multiple endocrine neoplasia type 1 (MEN-1)-associated insulinoma are not well described. Herein, we compared demographics, neoplasm characteristics, presentation, and survival in patients with sporadic vs MEN-1 insulinomas including benign and malignant disease. A retrospective study identified insulinoma patients. MEN-1 was defined based on genetic testing or clinically in patients with 2 or more primary MEN-1 tumor types. A total of 311 patients were identified: 84% benign and 16% malignant. The incidence of malignancy was similar (18% vs 16%, MEN-1 vs sporadic, p = 0.76). Within malignant patients, the median (interquartile range) age was 33 (25 ,44) years in MEN-1 vs 54 (41, 70) years in sporadic insulinoma (p = 0.04). There was no difference in sex or tumor size between MEN-1 and sporadic malignant insulinoma (p &gt; 0.05). Of the 260 patients with benign insulinoma, 7% had MEN-1 syndrome. MEN-1 patients presented with insulinoma at a younger age: median (interquartile range) age was 38 (24, 49) years vs 52 (43, 65) years (p &lt; 0.01). Resection of benign insulinoma was performed in 78% of the MEN-1 and 94% of the sporadic group (p = 0.03). Resected benign tumors were larger in the MEN-1 group: 2.0 (1.65, 2.45) cm vs 1.5 (1.2, 2.0) cm, respectively (p = 0.03). Concurrent insulinomas were more common in MEN-1 (17% vs 2%; p &lt; 0.01). MEN-1 patients present with insulinoma at younger age and have larger benign pancreatic lesions at the time of resection compared with sporadic neoplasms. Younger patients and those with multifocal pancreatic neuroendocrine tumor in the setting of endogenous hyperinsulinism should be evaluated for MEN-1.

Recidiverende hypoglykemie bij een patiënt zonder diabetes mellitus: een casusbespreking

Recurrent hypoglycemia in a patient without diabetes mellitus: a case report Hypoglycemia is an uncommon clinical problem in patients not being treated for diabetes mellitus. The presence of a hypoglycemic disorder in a person without diabetes mellitus should only be suspected in those patients in whom Whipple’s triad is documented. In this case report, the diagnostic exploration of a 79-year-old nondiabetic woman who presented with recurrent deep hypoglycemia, is described. The diagnosis of an insulinoma was established based on extensive laboratory testing (glucose, insulin, C-peptide, beta-hydroxybutyrate, proinsulin and sulfonylurea/meglitinide screening), a provocative fasting test and finally by localizing the tumor by means of magnetic resonance imaging. An insulinoma is a rare pancreatic islet cell tumor which may cause endogenous hyperinsulinism with frequent life-treating hypoglycemia, for which surgical enucleation is considered to be the therapy of choice. This case highlights the challenges endocrinologists face in the differential diagnosis of endogenous hyperinsulinism.

P-209 Management of insulinoma, changing trends in developing world

Insulinoma is uncommon endocrine tumors that have a prevalence of around 1 per 100,000 person-years. However; they represent the most common functioning endocrine tumor of the pancreas and is the main cause for hypoglycemia due to endogenous hyperinsulinism. In the presence of significant financial constraints in the patient population pancreatic insulinoma's management is difficult. In last 20 years development in diagnosis and surgery minimize complications.

Hypoglycemia in Non-Diabetic Patient: Report of Two Cases of Insulinoma

Background: Insulinoma is a B-cell tumor of the islets of the pancreas with an incidence of 4 per 1 million people per year, which produces excess insulin and can cause symptoms related to hypoglycemia at the level of the central nervous system or symptoms related to excess release of compensatory catecholamines. The presence of hypoglycemia, elevated insulin, proinsulin, and c-peptide levels suggest endogenous hyperinsulinism, which together with imaging findings suggestive of neuroendocrine tumor, allow establishing the diagnostic impression of Insulinoma. Cases report: Patients with neuroglycopenic symptoms, biochemical profile of hypoglycemia, endogenous hyperinsulinemia and radiological finding compatible with insulinoma are reported, who were treated by surgical resection of the tumor, with complete resolution of the initial symptoms. Conclusion: The clinical presentation, diagnosis and treatment of insulinoma represents a clinical challenge, since it is a rare pathology and the delay in diagnosis can have catastrophic consequences for the patient, stories such as permanent brain damage and death.