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Obesity Research & Clinical Practice 2016Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) due to the changes in gut hormonal... (Review)
Review
Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) due to the changes in gut hormonal milieu. Physicians should be aware of this complication to ensure timely and effective treatment of post-RYGB patients, who present to them with hypoglycemic symptoms. Possible causes of hypoglycemia in these patients include late dumping syndrome, nesidioblastosis and rarely insulinoma. Systematic evaluation including history, biochemical analysis, and diagnostic testing might help in distinguishing among these diagnoses. Continuous glucose monitoring is also a valuable tool, revealing the episodes in the natural environment and can also be used to monitor treatment success. Treatment should begin with strict low carbohydrate diet, followed by medication therapy. Therapy with diazoxide, acarbose, calcium channel blockers and octreotide have been proven to be beneficial, but the response apparently is highly variable. When other treatment options fail, surgical options can be considered.
Topics: Bariatric Surgery; Humans; Hyperinsulinism; Hypoglycemia; Obesity, Morbid
PubMed: 26522879
DOI: 10.1016/j.orcp.2015.07.003 -
Frontiers in Endocrinology 2020Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and...
Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma. The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels ( < 0.0001) and reduction of nocturnal hypoglycemia episodes ( = 0.0002). This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.
Topics: Adult; Blood Glucose; Circadian Rhythm; Congenital Hyperinsulinism; Diagnosis, Differential; Female; Humans; Hypoglycemia; Insulinoma; Nesidioblastosis; Pancreatectomy; Pancreatic Neoplasms; Starch
PubMed: 32047477
DOI: 10.3389/fendo.2020.00010 -
Polish Journal of Pathology : Official... 2017Congenital and adult-onset hyperinsulinism (CHI) must be taken under consideration in the differential diagnosis of hypoglycaemia symptoms with endogenous... (Review)
Review
Congenital and adult-onset hyperinsulinism (CHI) must be taken under consideration in the differential diagnosis of hypoglycaemia symptoms with endogenous hyperinsulinism, especially in cases in which there was failure to find an insulinoma. Histological examination is necessary for a definitive diagnosis. CHI is a disorder with three histopathological variants: focal CHI, diffuse CHI, and atypical CHI. These variants are clinically indistinguishable. According to published statistics, 0.5 to 5% of nesidioblastosis cases occur in adults. Clinical manifestation ranges from mildly symptomatic up to life-threatening hypoglycaemia. Early diagnosis and treatment are important in young and very young patients because early treatment accounts for favourable mental outcomes.
Topics: Female; Humans; Hyperinsulinism; Infant; Male; Middle Aged; Nesidioblastosis
PubMed: 29025242
DOI: 10.5114/pjp.2017.69684 -
Endocrinology, Diabetes & Metabolism... Dec 2022Adult-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...
SUMMARY
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.
LEARNING POINTS
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.
PubMed: 36571473
DOI: 10.1530/EDM-22-0361 -
World Journal of Gastroenterology Jan 2011Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia... (Review)
Review
Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults, which may or may not be associated with bariatric surgery. α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia. Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels, and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.
Topics: Adult; Aged; Animals; Endocrine System; Female; Humans; Hyperinsulinism; Hyperplasia; Hypoglycemia; Insulin-Secreting Cells; KATP Channels; Male; Mice; Middle Aged; Neuroendocrine Tumors; Pancreas; Phenotype; Receptors, Glucagon
PubMed: 21245985
DOI: 10.3748/wjg.v17.i2.137 -
Journal of Nuclear Medicine : Official... Jul 2021The glucagon-like peptide-1 receptor (GLP-1R) is an emerging target due to its high expression in benign insulinomas as well as in islet cell hypertrophia/hyperplasia...
The glucagon-like peptide-1 receptor (GLP-1R) is an emerging target due to its high expression in benign insulinomas as well as in islet cell hypertrophia/hyperplasia (nesidioblastosis) and pancreatic β-cells. In 2008, occult insulinomas were localized for the first time in men using the metabolically stable radiolabeled glucagon-like peptide-1 (GLP-1) agonist [Lys(Ahx-DTPA-In)NH]-exendin-4 (In-DTPA-exendin-4). Afterward, several radiopharmaceuticals for GLP-1R PET/CT imaging were synthesized and evaluated, for example, [Nle,Lys(Ahx-DOTA-Ga)NH]-exendin-4 (Ga-DOTA-exendin-4), [Cys(MAL-NOTA-Ga)NH]-exendin-4 (Ga-NOTA-exendin-4), and [Lys(NODAGA-Ga)NH]-exendin-4 (Ga-NODAGA-exendin-4). Several prospective comparison studies provided evidence that GLP-1R PET/CT is significantly more sensitive than contrast-enhanced MRI (ceMRI), contrast-enhanced CT (ceCT), GLP-1R SPECT/CT, somatostatin receptor PET/CT, and SPECT/CT in the detection of benign insulinomas, and insulinomas in the context of multiple endocrine neoplasia type 1. As a result, the European Neuroendocrine Tumor Society guidelines recommend GLP-1R imaging or selective intraarterial calcium stimulation and venous sampling (ASVS) in patients for whom there is a clinical suspicion of having an insulinoma but who have a negative ceMRI/ceCT or negative endoscopic ultrasound. Furthermore, there is growing evidence that GLP-1R PET/CT can visualize and localize adult nesidioblastosis. This is clinically relevant as the distinction between focal and diffuse nesidioblastosis is critical in directing a therapeutic strategy in these patients. Prospective studies have proven the clinical relevance of GLP-1R imaging as it is often the only imaging modality able to localize the insulinoma or nesidioblastosis. It is therefore likely that this noninvasive imaging modality will replace the invasive localization of insulinomas using ASVS. More experimental indications for GLP-1R imaging include the diagnosis of an insulinoma/nesidioblastosis in patients with postprandial hypoglycemia after bariatric bypass surgery and monitoring β-cells in patients with brittle type 1 diabetes after islet-cell transplantation. We believe that these indications and possibly future indications will bring GLP-1R imaging to the clinic.
Topics: Acetates; Animals; Glucagon-Like Peptide-1 Receptor; Heterocyclic Compounds, 1-Ring; Insulinoma; Positron Emission Tomography Computed Tomography
PubMed: 34230073
DOI: 10.2967/jnumed.120.246009 -
Acta Medica Portuguesa Jun 1995The islets of Langerhans provide energy storage and disposal, and protection from plasma glucose excursions, especially hypoglycemia. Insulin-dependent diabetes mellitus... (Review)
Review
The islets of Langerhans provide energy storage and disposal, and protection from plasma glucose excursions, especially hypoglycemia. Insulin-dependent diabetes mellitus (IDDM) results from autoimmune beta-cell damage. Prevention of IDDM has already been achieved in animal investigation and some centers are now screening and treating individuals at high risk for developing IDDM. Immunosuppressive drugs can induce transient remission of recent-onset IDDM. Intensive insulin treatment of IDDM delays the onset and slows the progression of long-term complications. Non-insulin dependent diabetes mellitus (NIDDM) is the result of beta-cell malfunction and is strongly associated with X syndrome. Diet and exercise are of undoubted importance in NIDDM prevention and treatment. Functional endocrine tumors of the pancreas (FET) are rare hormone and peptide-secreting neoplasms. These peptides may or may not occur naturally in the islets. FETs often occur with multiple endocrine neoplasia 1 (MEN 1) so that MEN-1 screening should always be performed, and extended to family members whenever diagnosed. Drugs--alcohol, insulin and sulfonilureas--are the main cause of hypoglycemia. Insulinoma is the main cause of post-absorptive organic hypoglycemia. Non islet-cell tumors seldom cause hypoglycemia. Insulinoma often is a solitary tumor, but it may be multicentric and may coexist with cell hyperplasia and nesidioblastosis. Symptoms of neuroglycopenia may be mistaken for neuropsychiatric disease. The diagnosis is based on confirmation of post absorptive hypoglycemia and hyperinsulinism. Gastrinoma causes Zollinger-Ellison syndrome (ZES) which is characterized by fulminating peptic ulcer disease. The tumor is often malignant, and it may be multicentric and may occur with cell hyperplasia and nesidioblastosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adenoma, Islet Cell; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Islets of Langerhans; Multiple Endocrine Neoplasia Type 1; Zollinger-Ellison Syndrome
PubMed: 7653306
DOI: No ID Found -
Biomedicines Jun 2023Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by... (Review)
Review
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.
PubMed: 37371827
DOI: 10.3390/biomedicines11061732 -
The Journal of Clinical Endocrinology... Mar 2016Congenital hyperinsulinism (HI) is the most common cause of hypoglycemia in children. The risk of permanent brain injury in infants with HI continues to be as high as... (Review)
Review
CONTEXT
Congenital hyperinsulinism (HI) is the most common cause of hypoglycemia in children. The risk of permanent brain injury in infants with HI continues to be as high as 25-50% due to delays in diagnosis and inadequate treatment. Congenital HI has been described since the birth of the JCEM under various terms, including "idiopathic hypoglycemia of infancy," "leucine-sensitive hypoglycemia," or "nesidioblastosis."
EVIDENCE ACQUISITION
In the past 20 years, it has become apparent that HI is caused by genetic defects in the pathways that regulate pancreatic β-cell insulin secretion.
EVIDENCE SYNTHESIS
There are now 11 genes associated with monogenic forms of HI (ABCC8, KCNJ11, GLUD1, GCK, HADH1, UCP2, MCT1, HNF4A, HNF1A, HK1, PGM1), as well as several syndromic genetic forms of HI (eg, Beckwith-Wiedemann, Kabuki, and Turner syndromes). HI is also the cause of hypoglycemia in transitional neonatal hypoglycemia and in persistent hypoglycemia in various groups of high-risk neonates (such as birth asphyxia, small for gestational age birthweight, infant of diabetic mother). Management of HI is one of the most difficult problems faced by pediatric endocrinologists and frequently requires difficult choices, such as near-total pancreatectomy and/or highly intensive care with continuous tube feedings. For 50 years, diazoxide, a KATP channel agonist, has been the primary drug for infants with HI; however, it is ineffective in most cases with mutations of ABCC8 or KCNJ11, which constitute the majority of infants with monogenic HI.
CONCLUSIONS
Genetic mutation testing has become standard of care for infants with HI and has proven to be useful not only in projecting prognosis and family counseling, but also in diagnosing infants with surgically curable focal HI lesions. (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET scans have been found to be highly accurate for localizing such focal lesions preoperatively. New drugs under investigation provide hope for improving the outcomes of children with HI.
Topics: Congenital Hyperinsulinism; Humans; Infant, Newborn; Insulin; Insulin Secretion; KATP Channels
PubMed: 26908106
DOI: 10.1210/jc.2015-3651 -
Case Reports in Endocrinology 2022Nesidioblastosis is a rare pancreatic disorder involving enlarged beta cells throughout the pancreas, causing elevated insulin production. We present the case of a...
Nesidioblastosis is a rare pancreatic disorder involving enlarged beta cells throughout the pancreas, causing elevated insulin production. We present the case of a 53-year-old woman with the initial symptom of fasting hypoglycemia. No pancreatic lesions were indicated on computed tomography and magnetic resonance imaging scans, and an octreotide scan was negative for insulinoma. Selective arterial calcium stimulation (SACST) showed increased insulin production from the stimulation of 3 out of 5 arteries. The SACST results suggested a diagnosis of nesidioblastosis, which was confirmed by histopathology after a subtotal distal pancreatectomy. The patient has normal glucose tolerance after surgery with no further problems of hypoglycemia, indicating that this is a rare case of nesidioblastosis extending only partially through the pancreas.
PubMed: 36248221
DOI: 10.1155/2022/2802975