Hyperinsulinemic Hypoglycemia Research Articles

Insulin Autoimmune Syndrome: A Systematic Review.

Insulin autoimmune syndrome (IAS) is a rare endocrine disorder characterized by recurrent episodes of severe hypoglycemia, markedly elevated serum insulin, and positive insulin autoantibodies. In recent years, various countries have reported it one after another. It can be seen that we must pay attention to this disease. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. High levels of insulin autoantibodies are found in patients, and C-peptide is not parallel to insulin, which could be diagnostic. IAS is a self-limiting disease with a good prognosis. Its treatment mainly includes symptomatic supportive treatment, such as adjusting the diet and using acarbose and other drugs to delay the absorption of glucose to prevent hypoglycemia. For patients with severe symptoms, available treatments may include drugs that reduce pancreatic insulin secretion (such as somatostatin and diazoxide), immunosuppressants (glucocorticoids, zaprin, and rituximab), and even plasma exchange to remove autoantibodies from the body. This review provides a comprehensive analysis of the epidemiology, pathogenesis, clinical manifestations, diagnosis and identification, and monitoring and treatment management of IAS.

Pancreatic microexons regulate islet function and glucose homeostasis.

Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their abnormal function causes diabetes or hypoglycaemia. Here we uncover a conserved programme of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural programme that are particularly sensitive to SRRM3 levels. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in human and rat beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, mice harbouring mutations in Srrm3 display defects in islet cell identity and function, leading to hyperinsulinaemic hypoglycaemia. Importantly, human genetic variants that influence SRRM3 expression and IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk. Taken together, our data identify a conserved microexon programme that regulates glucose homeostasis.

A case of malign insulinoma diagnosed with liver metastasis

Abstract Introduction Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells and is the most common cause of hyperinsulinemic hypoglycemia. Herein, a rare case of metastatic insulinoma in which many treatment alternatives were used will be presented. Clinical Case A 52-year-old male patient with no known history of chronic disease applied to us with complaints of numbness in the hands, inability to wake up in the morning and fainting. The patient, who worked as a professional referee, stated that he went to football matches with sugar in his pocket and ate sugar when he felt bad during the football matches. The patient needed to eat many times during the day. It was learned that the patient was treated with the diagnosis of transient ischemic attack and vertigo in another hospital where he applied with these complaints. In our hospital, random glucose was determined as 30 mg/dl. Prolonged fasting test was performed. Plasma glucose: 28 md/dl, insülin: 30,81 Uıu/ml, c-peptid 6,17 ng/ml were measured at 6th hour of the test. In abdominal computarized tomography, a 6.5×9.5 cm mass in the tail section of the pancreas and a subcentimetric metastatic nodular lesion in liver were detected. The patient diagnosed with metastatic insulinoma and distal pancreatectomy and liver metastasectomy operations were performed. Pathological examination showed insulinoma in the pancreas and neuroendocrine tumor metastasis in the liver (figure 1). No hypoglycemia was seen after operation. In the postoperative 24th month, fasting plasma glucose: 176 mg/dl and HBA1c: 8.6 were found and diabetes mellitus was diagnosed, insulin detemir was started. At the postoperative 36th month, a metastatic nodular lesion was detected in the liver. Fine needle aspiration biopsy was performed and in pathological examination, neuroendocrine carcinoma metastasis is seen. Octreotide LAR 20 mg/month treatment was started. In the follow-up, another metastasis was detected in two separate foci in liver so, patient's treatment was changed to lanreotide 120 mg/month. Four sessions of radiofrequency ablation were performed to the metastatic liver lesions. The patient is still being followed up by us and has no complaints of hypoglycemia. Plasma glucose values are in the normal range and Hba1c varies between 7.1–7.6%. Conclusion Although insulinoma cases are mostly benign, metastatic cases can also be seen rarely. The main treatment of the disease is surgery. Somatostatin analogues can be used in postoperative recurrence or inoperable metastatic disease. Radiofrequency ablation has an important role in local treatment.

The use of selective arterial calcium stimulation test in the diagnosis of the hyperinsulinemic hypoglycemia

We examined the patients with hyperinsulinemic hypoglycemia who were performed non-invasive imaging techniques with doubtful or failed results. We compared the performances of the Selective Arterial Calcium Stimulation Test (SACST) and non-invasive imaging techniques. Eight patients with hyperinsulinemic hypoglycemia, performed SACST after evaluating with imaging modalities were examined retrospectively. Three patients were diagnosed with Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS), 4 with insulinoma, and 1 with autoimmune hypoglycemia after SACST. While the concordance between the SACST and surgery-proven pathology for insulinoma was 50% (2/4), the accuracy in the localization of insulinoma was 25%. Although SACST does not have high concordance with surgery-proven pathology and accuracy in the localization of insulinoma, it may be preferred in the differential diagnosis of hyperinsulinemic hypoglycemia in medical centers where other imaging techniques are not available, or in cases where other imaging methods obtain suspicious/inadequate diagnosis.

Successful Treatment of Congenital Hyperinsulinism Due to KJNJ11 Gene Mutation with Long-Acting Release Octreotide: A Case Report from the Arab Region

AbstractCongenital hyperinsulinism is a rare hereditary condition that is caused by various gene mutations related to the function of the pancreatic β-cells. It is characterized by dysregulation of insulin secretion leading to profound and recurrent hypoglycemia. Its clinical presentation, histology, response to treatment, and underlying genetic defects are variable making it a heterogeneous condition. Pancreatectomy is indicated in diazoxide un-responsive cases. However, surgical treatment is associated with the possibility of persistent hypoglycemia and iatrogenic diabetes. We report a 3 months old girl who presented with hyperinsulinemic hypoglycemia. She was born to consanguineous parents and had a history of four neonatal deaths in siblings. Whole exome sequencing detected a KCNJ11 variant c.350_352del p.(Phe117del) in a homozygous state. Pancreatic scan (positron emission tomography/computed tomography) showed a diffusely increased radioisotope uptake in the head and tail of the pancreas. She was resistant to diazoxide and nifedipine and was shifted to octreotide treatment through multiple daily subcutaneous injections initially. Treatment was changed to monthly depot injection of octreotide that resulted in euglycemia. She kept a normal rate of growth, insulin-like growth factor-1, and liver function. This case is an example of an alternative effective medical therapy that avoids major surgical intervention and prevents long-term complication of recurrent hypoglycemia and iatrogenic diabetes resulting after surgery.

The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

P167: Atypical Sotos syndrome with normal length and late hyperinsulinemic hypoglycemia presentation

P167: Atypical Sotos syndrome with normal length and late hyperinsulinemic hypoglycemia presentation

A Case of Hyperinsulinemic Hypoglycemia in Premature Infant Treated with Oral Diazoxide

Neonatal hyperinsulinism, whether permanent or transient, results in prolonged hypoglycemia, which increases the risk of hypoglycemic brain injury. Therefore, prompt diagnosis and management of hyperinsulinemic hypoglycemia is important. Drawing a “critical sample” at the time of hypoglycemia is useful for diagnosis. Genetic testing for defective insulin-regulating genes in pancreatic beta-cells might also be helpful in cases of prolonged hypoglycemia. High-calorie feeding or glucose infusion is necessary to maintain normoglycemia. Diazoxide is the treatment of choice for hyperinsulinism and should be continued until the hypoglycemia resolves. We describe a case of transient neonatal hyperinsulinemia hypoglycemia in a small-for-gestational-age preterm infant who underwent diazoxide treatment and achieved a favorable outcome.

Diazoxide for Neonatal Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension.

Hypoglycemia in neonates is associated with long-term neurodevelopmental effects. Hyperinsulinemic hypoglycemia (HH) is the most common cause of persistent hypoglycemia in neonatal intensive care units. Diazoxide is the only medication that is currently recommended for treatment of HH in neonates. However, the use of diazoxide in neonates is associated with pulmonary hypertension as an adverse effect. In this article, we review the literature on the mechanism of action and adverse effects with the use of diazoxide in neonatal hyperinsulinism. We then present a case series of neonates treated with diazoxide in our neonatal intensive care unit over a 5-year period. Among 23 neonates who received diazoxide, 4 developed pulmonary hypertension and 1 died. All infants who developed pulmonary hypertension were born preterm at less than 36 weeks gestation and had pre-existing risk factors for pulmonary hypertension. HH in preterm neonates, with pre-existing pulmonary hypertension or with risk factors for pulmonary hypertension requires thoughtful management.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

A case of severe hypoglycemia after gastric bypass surgery in a woman with nonalcoholic fatty liver disease (NAFLD)

Post-gastric bypass hypoglycemia is characterized by postprandial hypoglycemia with pancreatic islet-cell hypertrophy in patients who have undergone a bariatric surgery and may be prone to hypoglycemia due to NAFLD, obesity, and impaired insulin and glucagon secretion.We present the case of a 44-year-old obese woman with NAFLD who underwent a Roux-en-Y gastric bypass and years later presented with severe hypoglycemia. She was diagnosed with endogenous hyperinsulinemic hypoglycemia and beta-cell hyperplasia.Post-gastric bypass hypoglycemia is a scenario that will be faced more often; therefore, it is important to take it into account for a timely treatment.

Nesidioblastosis: an uncommon complication seen post Roux-en-Y gastric bypass.

Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication. Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially. The incidence is 0.1-0.3% of all post Roux-en-Y gastric bypass patients. The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases. Pathological specimen of pancreas will show diffuse hypertrophy of beta cells. Management includes acarbose and total or subtotal pancreatectomy, which can be curative. With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.

Abstract #1319041: Hyperinsulinism-Hyperammonemia Syndrome in a Toddler With Recurrent Episodes of Loss of Consciousness

Hyperinsulinism-hyperammonemia syndrome (HI/HA) is one of the causes of hyperinsulinemic hypoglycemia in young children, which is responsive to diazoxide and protein restriction. Hypoglycemia of various etiologies in young children can lead to impaired neurological development. Early diagnosis and hence accurate management, is extremely important to prevent significant sequelae. We present a case of HI/HA, showing the importance of implementing the accurate approach for hypoglycemia in reaching the right diagnosis.

Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience.

To evaluate and present the data regarding clinical, laboratory, radiological and the results of molecular genetic analysis of patients with hyperinsulinemic hypoglycemia in our clinics. A total of 9 patients with CHI followed at Istanbul Medipol University. Data related to gender, age at presentation, birth weight, gestational age, consanguinity, glucose and insulin levels at diagnosis, treatment modalities, response to treatment, the results of genetic analysis and radiological evaluation were gathered from the files. The oldest age at presentation was 6months. KATP channel mutation was detected in 55% (n: 5). Diazoxide unresponsiveness was seen in 55% (n: 5). Octreotide was effective in 3 of them. 18F-DOPA PET performed in 4 diazoxide unresponsive patients revealed focal lesion in 3 of them. Spontaneous remission rate was 66% (n:6). All the patients with normal genetic result achieved spontaneous remission. Spontaneous remission was even noted in diazoxide unresponsive patients and in patients with focal lesion on 18F-DOPA PET. Clinical presentation of patients with congenital hypereinsulinism is heterogeneous. Spontaneous remission rate is quite high even in patients with severe clinical presentation. It is important to develop methods that can predict which patients will have spontaneous remission. Reporting the clinical and laboratory data of each patient is important and will help to guide the management of patients with hyperinsulinemic hypoglycemia.

MEHMO syndrome: complexity of verifying the diagnosis

MEHMO syndrome (OMIM: 300148; ORPHA: 85282) is a disease appears by mental retardation, epilepsy seizures, hypogonadism, microcephaly, and obesity. Pathology is associated with mutations in the EIF2S3 gene located on the X chromosome and leads usually to serious disability of patients. The article presents a clinical observation of the case of the syndrome in two male cousins with microcephaly, manifested by a complex of endocrinopathies (hyperinsulinemic hypoglycemia, multiple adenohypophysis hormone deficiency) and accompanied by severe neurological abnormalities (epilepsy, spastic tetraparesis, optic nerve atrophy). The complexity of the diagnostic due to the rarity of this syndrome, is described.

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 >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 (>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.

OR03-4 Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery; Assessment of Novel Dosing Regimens in an Expanded Indication

Abstract Post-bariatric hypoglycemia (PBH) is a rare disease characterized by recurrent episodes of severe, symptomatic hyperinsulinemic hypoglycemia (HH). The predominant form occurs after Roux-en-Y gastric bypass (RYGB). However, severe cases also present after other upper-gastrointestinal procedures. The mechanisms mediating PBH have long been debated, though a critical role for excessive postprandial secretion of glucagon-like peptide-1 (GLP-1) has been established. Avexitide (exendin 9-39) is a first-in-class GLP-1 receptor antagonist in development for treatment of PBH. Prior studies with avexitide administration have shown normalization of postprandial insulin concentrations and reductions in the occurrence of symptomatic hypoglycemia. In the Phase 2 multicenter PREVENT trial, avexitide administered to post-RYGB patients at a total daily dose of 60 mg [30mg twice daily (BID) or 60mg once daily (QD)] for 28 days was well-tolerated and demonstrated significant reductions in the rates of hypoglycemia, symptoms, and percent time in hypoglycemia. Based on the favorable safety and tolerability profile and dose-response relationship observed, we sought to evaluate whether higher doses of avexitide may further enhance the pharmacodynamic response. In addition, we sought to extend the evaluation to patients with HH after vertical sleeve gastrectomy, esophagectomy, gastrectomy or Nissen fundoplication. In this Phase 2b, open label, cross over study (NCT04652479), eligible patients included males and females (>18 years of age; BMI ≤40 kg/m2) with a history of recurrent hypoglycemia refractory to medical nutrition therapy (MNT) and exhibiting at least two severe hypoglycemia events while adhering to MNT over a 14-day period. Metabolic and symptomatic parameters were assessed by self-monitoring of blood glucose (SMBG), e-Diary, and blinded continuous glucose monitor (CGM) during 14 days of MNT as compared to 14 days of MNT + avexitide administered by subcutaneous injection at a dose of 45mg BID and 90mg QD in crossover design and random order, for a total of 28-days of treatment. An interim analysis (mixed-effect model) at ∼50% completion was conducted (n=8). The primary and secondary endpoints were met with statistical significance. Compared with MNT alone, avexitide 45mg BID and 90mg QD reduced the rate of Level 1 hypoglycemia (SMBG<70 mg/dL) by 66% (p=0.022) and 74% (p=0.010); Level 2 hypoglycemia (SMBG <54 mg/dL) by 70% (p=0.003) and 93% (p=0.001); and Level 3 hypoglycemia (severe event characterized by altered mental and/or physical function requiring assistance) by 77% (p=0.002) and 93% (p=0.001), respectively. Objective assessment by blinded CGM corroborated SMBG/e-Diary results, demonstrating significant reductions in the rates of hypoglycemia and improvements in percent time in hypoglycemia. Responses were comparable across surgical subtypes. Greater improvements were consistently observed with once daily (90 mg QD) than twice daily (45 mg BID) dosing and exceeded those reported in the PREVENT trial. Avexitide was well-tolerated, with no serious adverse events. Complete study results will be presented. Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.

PSUN253 Cocaine Use Resulting in Inadvertent Sulfonylurea Overdose

Abstract Introduction Most street cocaine is cut with other substances to increase drug volume. Often, cutting agents are used that change or intensify the effects of the drug. We present a case in which sulfonylurea-laced cocaine resulted in life-threatening hypoglycemia. Clinical Case A 61-year-old male with a history of heart failure with reduced ejection fraction, moderate aortic stenosis, and substance abuse was found unconscious with a fingerstick of 25 mg/dL. He had no personal history of diabetes. No one in his household had diabetes, and he denied any use of insulin or oral anti-diabetic medications. In the emergency department, he had recurrent hypoglycemia despite D10 boluses, glucagon, oral glucose tablets, and a full meal. He required initiation of a continuous intravenous D10 drip, which was titrated to 250 mL/hr to maintain normoglycemia. The endocrinology service was consulted for further evaluation and treatment. The patient recalled smoking a new supply of cocaine prior to his current admission. He had been admitted to two other hospitals within the month prior with similar episodes of severe hypoglycemia. Biochemical evaluation during a prior hospitalization suggested hyperinsulinemic hypoglycemia and a CT abdomen did not visualize an insulinoma. However, diagnostic evaluation was not completed at that time as the patient left against medical advice.Tests during this hospitalization included a low serum glucose 42 mg/dL, high insulin 107 uIU/mL (normal <3), high proinsulin 42.8 pmol/L (normal <5 pmol/L), high c peptide 13 ng/mL (normal <0.6) and low beta-hydroxybutyrate 1.2 mg/dL (normal >2.7mg/dL), consistent with hyperinsulinemic hypoglycemia. Other results included negative insulin antibody, normal TSH, and appropriately elevated cortisol levels. Given desire to rapidly wean D10 drip to avoid volume overload, octreotide therapy was initiated. He received octreotide 50mcg subcutaneously three times over a span of 24 hours, and the D10 drip was discontinued. His sulfonylurea screen subsequently resulted positive for glipizide. Considering the timing of cocaine use preceding the onset of hypoglycemia, it was postulated that the hyperinsulinemic hypoglycemic event was due to use of cocaine that was intermixed with sulfonylurea. Conclusion In cases of hypoglycemia with a known history of illicit substance abuse, clinicians should consider the presence of contributing cutting agents, such as sulfonylureas. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Adult-onset nesidioblastosis: a challenging diagnosis revealed by glucagon-like-peptide-1 receptor imaging

A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. 68Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months. Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia. The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different. 68Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia. Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis. Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.

PMON313 Hyperinsulinemic Hypoglycemia and Growth Hormone Deficiency Secondary to 20p11 Deletion

Abstract Introduction Hyperinsulinism (HI) and growth hormone deficiency (GHD) are known causes of hypoglycemia but not commonly found together. We present a 4-month-old boy with hypoglycemia found to have both HI and GHD with subsequent genetic diagnosis of 20p11 deletion. This deletion has been associated with panhypopituitarism. This case represents a few to report HI as a manifestation of this deletion. Treatment with both recombinant human growth hormone (rhGH) and Diazoxide led to blood glucose (BG) normalization. Clinical Case A 4-month-old, full-term, large for gestational age (96th percentile), born to a nondiabetic mother presented with hypoglycemic seizures. He had transient hypoglycemia at birth, normal newborn screen, and exclusively breastfeeding with normal growth and development. He had a negative 60-hour video EEG. Further work-up was significant for serum glucose of 54 mg/dL despite blood draw being 20 minutes after a breastfeed, prompting endocrinology evaluation. Physical exam showed no dysmorphism and normal genitalia. He had a serum glucose of 39 mg/dL while asymptomatic. Critical sample revealed detectable insulin (3.2 mcIU/mL), low beta hydroxybutyrate (145.6 mcmol/L) and low growth hormone (GH) (4.2 ng/dL). He had normal cortisol, lactic acid and ammonia. A glucagon challenge showed an increase in BG of 26 mg/dL (35-->61 mg/dL). He had a GH stimulation test with arginine (peak GH 3.8 ng/dL) and glucagon (peak GH 6.6 ng/dL). He had mildly elevated liver enzymes that resolved on repeat testing. Plasma amino acid, plasma acylcarnitine profile, urine organic acids, and brain MRI were normal. He was initially started on rhGH with continued hypoglycemia, hence, Diazoxide, and chlorothiazide were added. His BG was monitored until dextrose infusion was successfully weaned, while maintaining normoglycemia. Genetic testing with next-generation sequencing revealed 20p11.22-p11.21 deletion. He was discharged on Diazoxide (12 mg/kg/day), chlorothiazide, and rhGH (0.27 mg/kg/week). Conclusion It is important to determine the cause of hypoglycemia so specific treatment can be provided. HI is a common cause of hypoglycemia in infants due to abnormal insulin secretion in the pancreatic beta cells. GHD can also cause hypoglycemia and be associated with other pituitary hormone deficiencies. Evaluation of our patient's hypoglycemia revealed HI, GHD and 20p11 deletion. This deletion has been associated with hypoglycemia due to GHD and few reports with HI. This patient will need to be regularly screened for other pituitary hormone abnormalities. Other features of 20p11 deletion include cognitive delay, craniofacial dysmorphisms, gastrointestinal and genitourinary anomalies. While hypoglycemia is often the result of a single cause, this case shows that there are pathological conditions that can present with both GHD and HI, so the differential diagnosis for hypoglycemia should remain broad. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.