Endogenous Hyperinsulinemic Hypoglycemia Research Articles

MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia.

Glucose is the main substrate utilized by the brain and as such multiple regulatory mechanisms exist to maintain glucose concentrations. When these mechanisms fail or are defective, hypoglycemia ensues. Due to these robust mechanisms, hypoglycemia is uncommon and usually occurs in the setting of the treatment of diabetes using glucose-lowering agents such as sulfonylureas or insulin. The symptoms of hypoglycemia are non-specific and as such it is important to confirm hypoglycemia by establishing the presence of Whipple's triad before embarking on an evaluation for hypoglycemia. When possible, evaluation of hypoglycemia should be carried out at the time of spontaneous occurrence of symptoms. If this is not possible then one would want to create the circumstances under which symptoms occur. In cases where symptoms occur in the post absorptive state, a 72-h fast should be performed. Likewise, if symptoms occur after a meal then a mixed meal study may be the test of choice. The causes of endogenous hyperinsulinemic hypoglycemia include insulinoma, post-bariatric hypoglycemia and noninsulinoma pancreatogenous hypoglycemia syndrome. Autoimmune hypoglycemia syndrome is clinically and biochemically similar to insulinoma but associated with high levels of insulin antibodies and plasma insulin. Other important causes of hypoglycemia include medications, non-islet cell tumors, hormonal deficiencies, critical illness and factitious hypoglycemia. We provide an overview of the pathogenesis and management of hypoglycemia in these situations.

68Ga-Exendin-4 PET/CT in Evaluation of Endoscopic Ultrasound–Guided Ethanol Ablation of an Insulinoma

A 32-year-old man with endogenous hyperinsulinemic hypoglycemia was clinically diagnosed with an insulinoma. Conventional imaging result was negative, and a previous exploratory laparotomy with distal pancreatectomy failed to detect the tumor. Ga-exendin-4 PET/CT showed a lesion with intense radioactivity in the head of the pancreas suggestive of an insulinoma, and endoscopic ultrasound-guided ethanol ablation was performed. Postablation evaluation with Ga-exendin-4 PET/CT showed markedly decreased radioactivity of the tumor. The symptoms and blood glucose monitoring also suggested partial response of the insulinoma.

68Ga-exendin-4 PET/CT for the localization of insulinomas

Objective To determine whether glucagon-like peptide-1 (GLP-1) receptor PET/CT with 68Ga-exendin-4 is accurate in localizing insulinomas, by comparing with conventional imaging techniques. Methods In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia from March 2014 to November 2016 were recruited consecutively. 68Ga-exendin-4 PET/CT, CT, MRI, endoscopic ultrasound (EUS), and SSTR imaging were performed before elective surgery. Surgical pathology results were considered as the gold standard. Sensitivity based on patient-analysis and positive predictive value (PPV) based on lesion-analysis were calculated and compared using χ2 test and generalized score test. Results A total of 109 patients were recruited (47 males, 62 females; average age (45.1±14.8) years), and 96 of them with insulinomas proved pathologically were included in the main assessment. Thirteen patients with positive 68Ga-exendin-4 PET/CT findings did not undergo surgical intervention. Based on patient-analysis, the sensitivities of 68Ga-exendin-4 PET/CT, CT, MRI, EUS and SSTR imaging for detecting insulinomas were 98.96%(95/96), 81.25%(78/96), 79.41%(54/68), 81.40%(35/43) and 21.84%(19/87), respectively. Based on lesion-analysis, the PPV of the above 5 methods were 100%(102/102), 97.56%(80/82), 95.16%(59/62), 83.72%(36/43) and 90.48%(19/21), respectively. 68Ga-exendin-4 PET/CT showed the highest diagnostic sensitivity than others (all P<0.01) and higher PPV than MRI, EUS and SSTR imaging (all P<0.05). Conclusion 68Ga-exendin-4 PET/CT is a highly sensitive imaging technique for detection of insulinoma. Key words: Insulinoma; Positron-emission tomography; Tomography, X-ray computed; Glucagon-like peptide 1; Gallium radioisotopes

Decreased levels of Fibroblast Growth Factor 21 are correlated with improved hypoglycemia in patients with insulinoma

Fibroblast growth factor-21 (FGF-21) improves insulin sensitivity and lipid metabolism in obese or diabetic animal models and has been proposed as a potential therapeutic agent for treating T2DM, obesity, and their related complications. However, little is known about the changes of FGF21 levels in response to endogenous hyperinsulinemic hypoglycemia. To explore its relationship with parameters of glucose metabolism in patients with insulinoma, eleven subjects with pathological insulinoma and twenty-two healthy subjects were recruited for this study. Interestingly, we found that the serum FGF21 levels increased significantly in patients with insulinoma at baseline compared with the control group (381.36 ± 107.12 vs. 62.59 ± 10.48 pg/mL; P = 0.001). Furthermore, FGF21 was positively correlated with insulin (r = 0.80, P = 0.003) and proinsulin (r = 0.72, P = 0.012) in subjects with insulinoma. Multiple stepwise regression analysis showed that FGF21 was independently associated with insulin (β = 0.80, P = 0.003). In addition, FGF21 decreased significantly after surgery, and its change was still correlated positively with the changes in insulin (r = 0.61, P = 0.048) and proinsulin (r = 0.84, P = 0.001). These findings suggested that the serum FGF21 levels could be involved in a complex adaptive response to insulin secretion and glucose metabolism in humans.

"Riding High on Low Fuel" - Our Experience with Endogenous Hyperinsulinemic Hypoglycemia.

Introduction:Endogenous hyperinsulinemic hypoglycemia (EHH) is a condition in which the insulin levels are inappropriately high in the presence of low plasma glucose.Materials and Methods:We did a retrospective analysis of case records of those patients admitted and evaluated for EHH from June 2004 to June 2016 in our center, excluding those that were diagnosed with reactive hypoglycemia. We collected data regarding demographics, clinical presentation, laboratory results, localization techniques, and treatment administered.Results:Sixteen patients who were admitted for evaluation based on history suggestive of repeated hypoglycemic episodes were included in the study. All but one pregnant patient was subjected to a supervised fast in the hospital. All patients developed hypoglycemia (defined using Whipple's triad) within the first 24 h. Three patients had autoimmune hypoglycemia which differed significantly from insulinoma-mediated hypoglycemia in certain clinical and laboratory parameters. They were older in age with marked fluctuations in the 24 h glucose profile ranging from frank hypoglycemia to frank hyperglycemia. The insulin levels were markedly elevated in this group of patients along with a significantly elevated insulin C peptide molar ratio (ICMR) when compared with patients with insulinoma-mediated hypoglycemia.Conclusions:Although insulinoma is the most common cause of EHH, autoimmune hypoglycemia should be considered as a differential diagnosis, particularly in older individuals with plasma glucose values increasing to the hyperglycemic range. Degree of elevation of insulin levels and ICMR may provide additional clues. Overall, the survival and prognosis of patients with EHH are excellent.

Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma

Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Histologically, diffuse islet hyperplasia with increased number and size of islet cells is present and confirms the diagnosis. Differentiating NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy is the procedure of choice; however, recurrence of symptoms, although less debilitating, occurs commonly. Medical management with diazoxide, verapamil and octreotide can be used for persistent symptoms. Ultimately, near-total or total pancreatectomy may be necessary. We report a case of a 67-year-old male with hypoglycemia in whom preoperative workup, including computerized tomography abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH instead.

Imagerie des récepteurs du GLP-1 dans l’exploration des sécrétions inappropriées d’insuline

Endogenous hyperinsulinemic hypoglycemia is a rare disorder (incidence 2–4/Mio/year). In adult patients, the differential diagnosis includes benign and malignant insulinoma, insulinoma in the context of MEN-1 and nesidioblastosis whereby benign insulinoma is the most frequent diagnosis. The preoperative localization of benign insulinomas is challenging using conventional imaging procedures since these lesions are small (0.5–2 cm). GLP-1R imaging (SPECT/CT and PET/CT) using 111 In-DOTA-exendin-4 and a 68 Ga-DOTA-exendin-4, respectively and is an emerging technique targeting the GLP-1R expressed in very high density on insulinomas. All patients included in the prospective studies had a confirmed endogenous hyperinsulinemic hypoglycemia with neurogylcopenic symptoms. GLP-1R imaging using SPECT/CT ( n = 30) showed a sensitivity of 95% in detecting insulinomas (gold standard: histology), whereas conventional imaging exhibited a sensitivity of 47%. The follow-up study that compared GLP-1R SPECT/CT with PET/CT technique (ongoing study) confirmed the high sensitivity of this imaging procedure with an advantage for the PET/CT technique. Patients with NEM-1 develop multicentric pancreatic islet tumors, the most common functional ones being gastrinomas and insulinomas. Surgery is the only treatment option. However, the surgical intervention should be limited as surgery cannot cure patients with MEN-1. It is therefore, mandatory to correctly localize tumor lesions. The experience with 6 patients suggests that adding GLP-1R imaging to conventional imaging is a helpful tool in differentiating insulinomas from other pancreatic islet lesions. Adding GLP-1R imaging to conventional imaging is a very useful technique in preoperatively localizing benign insulinomas and insulinomas in the context of MEN-1.

Localization of benign insulinomas using glucagon-like peptide-1 receptor (GLP1-R) SPECT/CT and PET/CT in a prospective clinical study

358 Objectives The aim of our study is to compare the detection rate of GLP-1R PET/CT and GLP-1R SPECT/CT in patients with a biochemically proven endogenous hyperinsulinemic hypoglycemia highly suspicious for an insulinoma. Preliminary results of an ongoing study are reported. Methods Thirty-three patients (25 females, 8 males, age range 18-80 years, mean 49 years) with neuroglycopenic symptoms due to endogenous hyperinsulinemic hypoglycemia were enrolled (ClinicalTrials.gov, NCT02127541). The patients received a SPECT/CT 72 hours after injection of 111In-DOTA-exendin-4 and PET/CT 2.5 hours after injection of 68Ga-DOTA-exendin-4 in a randomized fashion within a week. Histological diagnosis after surgery was used as reference standard. Two expert readers reviewed PET/CT and SPECT/CT data in a standardized, randomized and blinded fashion. Results Previously performed cross-sectional imaging (CT/MRI) was negative or not conclusive in 25/33 (76%) of patients. So far 22 patients have been operated. In this collective, the histological diagnosis of a benign insulinoma was confirmed in 19 patients, 1 patient had adult islet cell hyperplasia. In 1 patient both intraoperative palpation as well as the histological diagnosis did not confirm an insulinoma. In 1 patient symptoms of endogenous hypoglycemia ceased postoperative but histological diagnosis did not confirm the diagnosis of a benign insulinoma or nesidioblastosis. Only this patient was excluded from evaluation as the final diagnosis remained unclear. Two patients refused surgery. Five patients are awaiting surgery. In 4 patients PET/CT, SPECT/CT as well as the previous performed conventional imaging did not find any suspicious lesion and were thus not operated up to date. In this interim analysis PET/CT showed an overall pooled sensitivity of 93 % SPECT/CT at 72 hours showed an overall pooled sensitivity of 75 % PET/CT was the only modality which correctly identified the area of islet cell hyperplasia (adult nesidioblastosis) within the pancreas. Conclusions Our interims analysis suggests that GLP-1R PET/CT performs better than GLP-1R SPECT/CT at a lower radiation dose and shorter examination time. GLP-1R PET/CT will be a useful diagnostic tool in patients where cross sectional imaging (CT/MRI) fails to localize the insulinoma.

Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics.

We aimed to determine the frequency of isoattenuating insulinomas, to investigate their clinicopathological features and to assess their regional pancreatic perfusion characteristics. Institutional review board approval was obtained, and patient informed consent was waived. From July 2010 to June 2014, 170 patients (66 male, 104 female) with endogenous hyperinsulinemic hypoglycemia underwent biphasic contrast-enhanced CT before surgery, and 129 of those patients also received preoperative whole-pancreas CT perfusion. A total of 181 tumours were proved histopathologically after surgery. Enhancement pattern and regional pancreatic perfusion characteristics were analyzed. Clinical features, tumour size and pathological grading were investigated. The frequency of isoattenuating tumours was 24.9%. Tumour size and WHO grading was not significantly different between isoattenuating and hyperattenuating tumours. Tumour-free regions had identical blood flow (BF) regardless of their location (p = 0.35). Isoattenuating tumour-harbouring regions had lower BF compared with hyperattenuating tumour-harbouring regions; both showed higher BF compared with tumour-free neighbourhood regions (all p < 0.01). For patients with isoattenuating tumours, the overall hospital stay was longer (p < 0.01). A substantial subset of insulinomas were isoattenuating on biphasic CT. CT perfusion showed higher BF in tumour-harbouring regions compared to tumour-free regions, providing a clue for tumour regionalization. • About a quarter of all insulinomas were isoattenuating on biphasic contrast-enhanced CT. • CT perfusion finds tumour-harbouring regions have higher blood-flow compared to tumour-free regions. • CT perfusion provides important information for tumour regionalization, for isoattenuating tumours.

Pattern of Weight Loss after Successful Enucleation of an Insulin-producing Pancreatic Neuroendocrine Tumor

We report the case of a patient with hypoglycemic symptoms and weight gain. Biochemical investigations revealed endogenous hyperinsulinemic hypoglycemia. A CT scan and MRI of the abdomen were initially not successful in localizing a pancreatic mass. However, an endoscopic ultrasound was able to demonstrate a pancreatic head mass. Enucleation of the mass resulted in clinical and biochemical improvement. This report also demonstrates the pattern of weight loss after surgery, showing an initial phase of gradual weight loss followed by a rapid loss of weight. This pattern of weight loss after successful removal of an insulin-producing pancreatic neuroendocrine tumor is a novel addition to the existing knowledge we have about this condition.

Selective Arterial Calcium Stimulation With Hepatic Venous Sampling Differentiates Insulinoma From Nesidioblastosis.

In adult patients with endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging, insulinoma and non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS) resulting from diffuse nesidioblastosis must be considered in the differential diagnosis. It is not known whether the biochemical results of selective arterial calcium stimulation (SACST) with hepatic venous sampling can differentiate insulinoma from diffuse nesidioblastosis. To determine the specificity of SACST with hepatic venous sampling in differentiating insulinoma from diffuse nesidioblastosis. Retrospective review (January 1996 to March 2014). Tertiary referral center. A total of 116 patients with biochemical evidence of endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging who were subsequently shown at surgery to have insulinoma (n = 42) or nesidioblastosis (n = 74) after undergoing SACST with hepatic venous sampling. SACST with hepatic venous sampling before pancreatic exploration. Receiver operating characteristic curves were generated from the biochemical results of SACST to determine the specificity of the maximum hepatic venous insulin concentration (mHVI) and the relative-fold increase in hepatic venous insulin concentration (rHVI) over baseline after calcium injection from the dominant artery in differentiating insulinoma from nesidioblastosis. The mHVI (21.5-fold; P < .001) and rHVI (3.9-fold; P < .001) were significantly higher in the insulinoma group compared to the nesidioblastosis group. The areas under the receiver operating characteristic curve for mHVI and rHVI were excellent (0.94; P < .0001) and good (0.83; P < .0001), respectively, for differentiating insulinoma from nesidioblastosis. mHVI cutoffs of > 91.5 and > 263.5 μIU/mL were 95 and 100% specific for insulinoma, respectively. A 19-fold increase in rHVI over baseline was 99% specific for insulinoma. These data suggest that the mHVI and rHVI at SACST may be useful in differentiating insulinoma from nesidioblastosis with high specificity in patients with hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging.

Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.

(111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

Adult onset nesidioblastosis treated by subtotal pancreatectomy.

Nesidioblastosis is a rare cause of non insulinoma pancreatogenous hypoglycemic syndrome seen in adults. It is characterized by postprandial hypoglycemia with high insulin and C-peptide levels without any detectable pancreatic lesion. The definitive diagnosis can be made only on histopathological examination of the resected specimen. We report a case of a 50-year-old lady presenting with hypoglycemic attacks being misdiagnosed preoperatively as insulinoma and treated with enucleation leading to recurrence of symptoms after 6 months. Later medical therapy was tried which failed and patient needed subtotal pancreatectomy for resolution of symptoms. Nesidioblastosis should be suspected in patients with endogenous hyperinsulinemic hypoglycemia without any detectable pancreatic tumor on preoperative imaging.

Clinical features and causes of endogenous hyperinsulinemic hypoglycemia in Korea.

BackgroundEndogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.MethodsTo evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.ResultsAmong the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.ConclusionThe results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Management of Refractory Noninsulinoma Pancreatogenous Hypoglycemia Syndrome with Gastric Bypass Reversal: A Case Report and Review of the Literature.

Background. Roux-en-Y gastric bypass (RYGB) is a commonly performed, effective bariatric procedure; however, rarely, complications such as postprandial hypoglycemia due to noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) may ensue. Management of refractory NIPHS is challenging. We report a case that was successfully treated with RYGB reversal. Case Report. A 58-year-old male with history of RYGB nine months earlier for morbid obesity presented for evaluation of postprandial, hypoglycemic seizures. Testing for insulin level, insulin antibodies, oral hypoglycemic agents, pituitary axis hormone levels, and cortisol stimulation was unrevealing. Computed tomography (CT) scan of the abdomen was unremarkable. A 72-hour fast was completed without hypoglycemia. Mixed meal testing demonstrated endogenous hyperinsulinemic hypoglycemia (EHH) and selective arterial calcium stimulation testing (SACST) was positive. Strict dietary modifications, maximal medical therapy, gastrostomy tube feeding, and stomal reduction failed to alleviate symptoms. Ultimately, he underwent laparoscopic reversal of RYGB. Now, 9 months after reversal, he has markedly reduced hypoglycemia burden. Discussion. Hyperfunctioning islets secondary to exaggerated incretin response and altered intestinal nutrient delivery are hypothesized to be causative in NIPHS. For refractory cases, there is increasing skepticism about the safety and efficacy of pancreatic resection. RYGB reversal may be successful.

Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques. In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically. Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0.011). (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI. Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Increased plasma β-hydroxybutyrate levels during the fasting test in patients with endogenous hyperinsulinaemic hypoglycaemia

The objective of the present study was to determine whether a plasma β-hydroxybutyrate (BOHB) level >2700 μmol/l during the 72-h fasting test is sufficient to rule out the diagnosis of endogenous hyperinsulinaemic hypoglycaemia (EHH). We retrospectively studied BOHB levels in 39 patients with EHH who had undergone a 72-H fasting test to make the diagnosis of EHH, and we compared EHH patients with BOHB levels 2700 MOL/L (group 1), EHH PATIENTS with BOHB levels 2700 MOL/L (group 2) and 59 controls (median glycaemia: 3.2 mmol/l and median BOHB: 6095 μmol/l). During a 72-h fasting test, nine patients (group 1) had BOHB levels >2700 μmol/l (median 6140 and range 2957-7824) and 30 patients (group 2) had BOHB levels <2700 μmol/l (median 542 and range 0-2607). In group 1, four patients had undergone partial pancreatectomy previously and were evaluated for the recurrence of hypoglycaemia, whereas none of the group 2 patients had been operated. The duration of the fasting test was longer in group 1 than in group 2 (P<0.0001), and at the end of the fasting test, plasma glucose concentrations were not significantly different (P=0.0617), but insulin (P=0.004), C-peptide (P=0.0015) and proinsulin (P=0.0038) levels were significantly lower in group 1 patients than in group 2 patients, suggesting lower insulin secretion and/or impaired glycaemic counter-regulation. During a fasting test, a BOHB level >2700 μmol/l is observed in some EHH patients, suggesting that BOHB levels cannot rule out the recurrence of EHH, in particular, after partial pancreatectomy.

PS13 - 63. Pasireotide prevents post-gastric bypass endogenous hyperinsulinaemic hypoglycaemia

Endogenous hyperinsulinaemic hypoglycaemia is a rare but serious complication of gastric bypass surgery occurring from a few months up to 8 years after surgery. A 50 year old woman developed frequent severe hypoglycaemic episodes with loss of consciousness usually one hour after meal 4 months after succesfull laparoscopic roux-eny gastric bypass (RYGB).

Octreotide-Treated Diabetes Accompanied by Endogenous Hyperinsulinemic Hypoglycemia and Protein-Losing Gastroenteropathy

Occurrence of hypoglycemia in diabetes patients is very rare. We report here a case of frequent hypoglycemic attacks caused by inappropriate endogenous hyperinsulinemia in a female patient with poorly controlled diabetes and protein-losing gastroenteropathy. The blood glucose profiles of the patient were unstable. Results of the fasting test performed to investigate the cause of hypoglycemia suggested endogenous hyperinsulinism. Repeated selective arterial calcium injection tests suggested that hyperinsulinemia might be extrapancreatic in origin. However, efforts to detect a responsible lesion such as insulinoma were unsuccessful. Octreotide was used for the treatment of hypoglycemia and protein-losing gastroenteropathy. After treatment, although her leg edema caused by hypoalbuminemia persisted, hypoglycemia almost disappeared.

Von der Frau, der das Essen nicht bekam

We report the case of a 59-year-old women with idiopathic insulin auto-immune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia. It is characterized by extremely high levels of insulin in the presence of high titers of insulin antibodies despite the absence of previous insulin injections. Early postprandial increase in glucose concentrations due to impaired insulin action resulting from the buffering effect of the antibodies and late postprandial hypoglycemia as a consequence of the dissociation of insulin from the antibodies was observed. A correct diagnosis is important to avoid unnecessary investigations and surgery in these patients who are best treated conservatively - with a good prognosis - by fractionating carbohydrate intake during the day.