Noninsulinoma Pancreatogenous Hypoglycemia Syndrome in a Patient With 1p36 Deletion Syndrome.

The 1p36 deletion syndrome involves a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. We report the case of a 21-year-old female patient with 1p36 deletion syndrome who was found to have noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after hospitalization for persistent falls. On admission, vital signs were normal and physical examination revealed a thin, nonverbal patient. During hospitalization and prolonged fasting (14-18 hours), she persistently developed hypoglycemia (serum glucose nadir 57 mg/dL [3.2 mmol/L] [70-100 mg/dL; 3.9-5.6 mmol/L]). Subjective symptoms of hypoglycemia were not confirmed due to patient's cognitive impairment. Hypoglycemic events continued despite feeding and dextrose-containing fluids. Further workup included a critical sample that revealed a serum glucose 59 mg/dL (3.3 mmol/L), insulin 20.6 µIU/mL (123.6 pmol/L [5-15 µIU/mL; 30.0-90 pmol/L]), proinsulin 33 pmol/L (3.6-22 pmol/L), C-peptide 1.74 ng/mL (0.58 nmol/L [0.8-3.85 ng/mL; 0.27-1.28 nmol/L]) and beta-hydroxybutyrate < 1.04 mg/dL (< 0.10 mmol/L; [< 4.2 mg/dL; < 0.4 mmol/L]). Insulin antibodies were negative. After confirmed insulin-mediated hypoglycemia, imaging studies followed. Pancreatic protocol abdominal computed tomography (CT), Ga-68 DOTATATE PET/CT scan, and endoscopic ultrasound found no pancreatic mass. Selective arterial calcium stimulation test showed a two-fold increase in insulin levels in 3/3 catheterized pancreatic territories. The patient started octreotide injections with resolution of hypoglycemia and was discharged on monthly lanreotide injections. To our knowledge, this is the first case reported of noninsulinoma pancreatogenous hypoglycemia in a patient with 1p36 deletion syndrome.

Diagnosis of pancreatic focal nesidioblastosis assisted by dual­nuclide tracer positron emission tomography/computed tomography: A case report.

Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults and its clinical features are similar to those of insulinoma with recurrent hypoglycemic attacks. The present study reports the case of a 48-year-old man who visited the Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a 5-year history of recurrent hypoglycemic symptoms such as dizziness and palpitations. Abdominal magnetic resonance imaging (MRI) showed a mass of ~1.2x1.0 cm in the head of the pancreas, which was suspected to be an insulinoma. For confirmation, the patient underwent both fluorine-18-fluorodeoxyglucose (18F-FDG) and gallium-68-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-teraacetic acid-d-Phel-Tyr3-Thr8-OC (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT), which showed a moderately increased uptake of 18F-FDG but no uptake of 68Ga-DOTATATE in the corresponding lesion. The patient subsequently underwent surgery to remove the lesion, which was pathologically confirmed as a pancreatic nesidioblastosis. This case showed that nesidioblastosis should be considered a differential diagnosis for insulinoma and that dual nuclear tracer PET/CT imaging is helpful for differentiating between the two. If conventional imaging techniques such as ultrasound, CT and MRI cannot identify the cause of hypoglycemia in future cases, dual-nuclide tracer PET/CT imaging should be considered.

Neoplasia endocrina múltiple tipo 1 en paciente con diagnóstico de nesidioblastosis. Presentación de un caso

Las neoplasias endocrinas múltiples engloban una serie de síndromes caracterizados por su origen genético y la afectación de una o más glándulas. Se describe el caso de un paciente masculino, de 23 años, con antecedentes de salud de nesidioblastosis diagnosticado a los 16 años de edad, quien acudió al Hospital General Docente Ambato por presentar convulsiones tónico clónicas, e hipoglucemia severa con posterior estatus epiléptico. Los estudios de laboratorio mostraron hiperparatiroidismo primario, y los de imagen identificaron lesiones sugerentes de adenoma paratiroideo e insulinoma de cabeza de páncreas. Después de analizar el caso, se identificaron dos criterios para plantear una neoplasia endocrina múltiple tipo 1: presencia de insulinoma e hiperparatiroidismo primario. Además de tratamiento con bifosfonato, se planificó interconsulta con el servicio de Genética, para estudio del paciente y familiares; y con Cirugía General, para programación de resolución quirúrgica. Debido a la poca frecuencia de esta enfermedad, resulta de interés describir el caso, con el objetivo de exponer las principales manifestaciones clínicas y conducta a seguir. Constituye una prioridad el diagnóstico de su causa en cada paciente.

Multiple endocrine neoplasias encompass a series of syndromes characterized by their genetic origin and the involvement of one or more glands. A 23-years-old male patient with a health history of nesidioblastosis diagnosed at 16 years of age, who attended the Ambato General Teaching Hospital with tonic-clonic seizures and severe hypoglycemia with subsequent epileptic status, is described. Laboratory studies showed primary hyperparathyroidism, and imaging identified lesions suggestive of parathyroid adenoma and insulinoma of the head of the pancreas. After analyzing the case, two criteria were identified to suggest multiple endocrine neoplasia type 1: presence of insulinoma and primary hyperparathyroidism. In addition to treatment with bisphosphonate, consultation with the Genetics service was planned for study of the patient and family members; and with General Surgery, for scheduling surgical resolution. Due to the infrequency of this disease, it is of interest to describe the case, with the aim of exposing the main clinical manifestations and conduct to follow. Diagnosing its cause in each patient is a priority.

Sugar Swing After Surgery: Hyperinsulinemic Hypoglycemia With Possible Nesidioblastosis After Roux-en-Y Gastric Bypass Surgery.

Bariatric surgery is a procedure performed to achieve weight loss and manage obesity. However, it can result in various complications including post-surgical hypoglycemia. Nesidioblastosis is a rare hypoglycemic syndrome marked by diffuse hyperplasia of pancreatic ß cells with distinct histologic features. Recent case reports have indicated an association of nesidioblastosis with certain bariatric procedures, often specifically linked to Roux-en-Y gastric bypass (RYGB) surgery. In this case report, we describe a 78-year-old male with a complex medical history who presented with altered mental status and severe hypoglycemia (13 mg/dL), despite having no history of diabetes or use of hypoglycemic medications. The patient's clinical condition improved after receiving a 50% intravenous dextrose injection and subsequently placed on a 10% dextrose infusion. Adrenal insufficiency was ruled out with normal cortisol level, and tests for ß-hydroxybutyrate, dehydroepiandrosterone (DHEA) sulfate, and hypoglycemia panels were all negative. However, further investigations were significant for elevated serum insulin, C-peptide, and proinsulin levels. The patient then underwent an abdominal computed tomography (CT) scan, which revealed a grossly normal liver, spleen, pancreas, and adrenal glands, along with evidence of prior gastric bypass surgery. Further evaluation confirmed a history of Roux-en-Y gastric bypass surgery, which was performed to address morbid obesity and obstructive sleep apnea. Following the procedure, the patient began experiencing hypoglycemic episodes. Subsequently, the patient was diagnosed with hyperinsulinemic hypoglycemia with possible nesidioblastosis. This diagnosis was made based on severe recurrent postprandial hypoglycemia, accompanied by elevated endogenous insulin production, and a pancreas that appeared grossly normal on imaging. The patient was treated with acarbose to prevent carbohydrate-driven blood sugar and insulin spikes, octreotide to inhibit insulin secretion, and dietary guidance to avoid high glycemic index foods. This case emphasizes the potential link between bariatric surgeries and metabolic disturbances, underscoring the importance of identifying uncommon hypoglycemic syndromes.

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult.

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), without previous bariatric surgery, is a rare form of hypoglycemia in adult patients and is associated with nesidioblastosis. Adult-onset nesidioblastosis in diabetic patients is rare and histologically identical to "non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)". Nesidioblastosis is rare in adults and clinically and biochemically mimics Insulinoma. In the literature, there have only been four cases of adult nesidioblastosis that followed diabetes mellitus. We report a case of nesidioblastosis in a 36-year-old diabetic female presenting with dizziness, sweating, and palpitations for three years. Selective non-invasive techniques failed to detect a tumor. Based on the pursuit of an insulinoma, a distal pancreatectomy specimen was received at our laboratory, and a diagnosis of nesidioblastosis was made. She is currently on follow-up with a favorable outcome. The definitive diagnosis of nesidioblastosis is made on a histological basis. The preferred form of treatment is pancreatic surgical resection. Nesidioblastosis should be taken into consideration in cases where diabetes transforms into hyperinsulinemic hypoglycemia.

Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens.

BACKGROUND: Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. METHODS: We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. RESULTS: There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. CONCLUSIONS: Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in ß-cells," has potential diagnostic value.

Pathological features in non-neoplastic congenital and adult hyperinsulinism: from nesidioblastosis to current terminology and understanding.

Nesidioblastoma and nesidioblastosis were terms given to neoplastic and non-neoplastic lesions of the pancreas associated with pancreatogenous hyperinsulinaemic hypoglycaemia. While nesidioblastoma was rapidly replaced by islet cell tumour, nesidioblastosis, defined as the proliferation of islet cells budding off from pancreatic ducts, was the diagnostic term associated with congenital hyperinsulinism of infancy (CHI) and adult non-neoplastic hyperinsulinaemic hypoglycaemia (ANHH). When it was shown that nesidioblastosis was not specific for CHI or ANHH, it was no longer applied to CHI but kept for the morphological diagnosis of ANHH. In severe CHI cases, a diffuse form with hypertrophic ß-cells in all islets can be distinguished from a focal form with hyperactive ß-cells changes in a limited adenomatoid hyperplastic area. Genetically, mutations were identified in several ß-cell genes involved in insulin secretion. Most common are mutations in the ABCC8 or KCNJ11 genes, solely affected in the diffuse form and associated with a focal maternal allelic loss on 11p15.5 in the focal form. Focal CHI can be localized by 18F-DOPA-PET and is thus curable by targeted resection. Diffuse CHI that fails medical treatment requires subtotal pancreatectomy. In ANHH, an idiopathic form can be distinguished from a form associated with gastric bypass, in whom GLP1-induced stimulation of the ß-cells is discussed. While the ß-cells in idiopathic ANHH are diffusely affected and are either hypertrophic or show only little changes, it is controversial whether there is a ß-cell increase or ß-cell hyperactivity in patients with gastric bypass. Recognizing morphological signs of ß-cell hyperactivity needs a good knowledge of the non-neoplastic endocrine pancreas across all ages.

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 ß-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.

An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS).

Neurovegetative and autonomic symptoms are common presentations of various diseases, ranging from psychosomatic to severe organic disorders. A 23-year-old man presented with a history of recurrent presyncope, dizziness, and tachycardia. Repeated diagnostic work-up in various clinical settings could not identify any definite cause for approximately eight years. However, the incidental detection of postprandial and exercise-induced hypoglycemia was suggestive of an insulin-related disorder. A 72 h plasma glucose fasting test revealed endogenous hyperinsulinism. Upon imaging studies, no tumor mass potentially indicating insulinoma could be detected. 68Ga-DOTA-Exendin-4 PET/CT showed diffuse tracer enrichment throughout the whole pancreas. A subtotal pancreatectomy was performed, and the diagnosis of diffuse, adult-onset nesidioblastosis was established histopathologically. This corresponds to the clinical findings of a functional ß-cell disorder, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). After nine months, the symptoms recurred, making complete pancreatectomy necessary. Postoperative laboratory evaluation exhibited no residual endogenous C-peptide production. This case illustrates the diagnostic challenges in patients presenting with unspecific, neurovegetative and autonomic symptoms with a severe and rare underlying cause.

Incidence, predictors and outcomes of redo pancreatectomy in infants with congenital hyperinsulinism: a 16-year tertiary center experience.

PURPOSE: Recurrent severe hypoglycemic attacks often persist even after performing pancreatectomy for medically unresponsive congenital hyperinsulinism (CHI). In this study, we present our experience with redo pancreatectomy for CHI. METHODS: We reviewed all children who underwent pancreatectomy for CHI between January 2005 and April 2021 in our center. A comparison was made between patients whose hypoglycemia was controlled after primary pancreatectomy and patients who required reoperation. RESULTS: A total of 58 patients underwent pancreatectomy for CHI. Refractory hypoglycemia after pancreatectomy occurred in 10 patients (17%), who subsequently underwent redo pancreatectomy. All patients who required redo pancreatectomy had positive family history of CHI (p = 0.0031). Median extent of initial pancreatectomy was lesser in the redo group with borderline level of statistical significance (95% vs. 98%, p = 0.0561). Aggressive pancreatectomy at the initial surgery significantly (p = 0.0279) decreased the risk for the need to redo pancreatectomy; OR 0.793 (95% CI 0.645-0.975). Incidence of diabetes was significantly higher in the redo group (40% vs. 9%, p = 0.033). CONCLUSION: Pancreatectomy with 98% extent of resection for diffuse CHI, especially with positive family history of CHI, is warranted to decrease the chance of reoperation for persistent severe hypoglycemia.

Adult focal ß-cell nesidioblastosis: A case report.

BACKGROUND: Nesidioblastosis usually refers to a series of clinical manifestations caused by the proliferation of ß-cells in pancreatic islets, and these clinical manifestations are hyperinsulinemia and persistent hypoglycemia. According to the size of the lesion, nesidioblastosis is divided into focal nesidioblastosis, diffuse nesidioblastosis and atypical nesidioblastosis, and its pathogenesis is still unclear. Nesidioblastosis is mainly seen in infants and rarely reported in adults, especially focal nesidioblastosis, which is difficult to distinguish from insulinoma. CASE SUMMARY: We report a case of adult focal ß-cell nesidioblastosis in which the preoperative diagnosis was insulinoma. The patient was a 48-year-old male who suffered from repeated morning and fasting palpitations, sweating, and severe disturbance of consciousness for 5 years. His blood glucose was found to be as low as 1.79 mmol/L during an attack. However, abdominal computed tomography showed no abnormalities. Magnetic resonance imaging and endoscopic ultrasonography demonstrated a nodular mass in the head of the pancreas, combined with hyperinsulinemia and high serum C-peptide. The patient was diagnosed with insulinoma and underwent Beger surgery; however, the postoperative pathological results showed nesidioblastosis. CONCLUSION: Although surgical resection is the preferred option for nesidioblastosis, some cases can be treated non-surgically. In order to increase clinicians' understanding of nesidioblastosis, it is necessary to review the pathogenesis, diagnosis and treatment of this disease.

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult

ABSTRACT Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), without previous bariatric surgery, is a rare form of hypoglycemia in adult patients and is associated with nesidioblastosis. Adult-onset nesidioblastosis in diabetic patients is rare and histologically identical to "non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)". Nesidioblastosis is rare in adults and clinically and biochemically mimics Insulinoma. In the literature, there have only been four cases of adult nesidioblastosis that followed diabetes mellitus. We report a case of nesidioblastosis in a 36-year-old diabetic female presenting with dizziness, sweating, and palpitations for three years. Selective non-invasive techniques failed to detect a tumor. Based on the pursuit of an insulinoma, a distal pancreatectomy specimen was received at our laboratory, and a diagnosis of nesidioblastosis was made. She is currently on follow-up with a favorable outcome. The definitive diagnosis of nesidioblastosis is made on a histological basis. The preferred form of treatment is pancreatic surgical resection. Nesidioblastosis should be taken into consideration in cases where diabetes transforms into hyperinsulinemic hypoglycemia.

Juvenile hyperinsulinism in a Maine Coon kitten.

Case summary: A 5.5 month-old intact male Maine Coon cat was presented to a referral hospital for a history of muscle fasciculations, lethargy and seizures associated with refractory hypoglycemia. Diagnostic testing for hypothyroidism, hyposomatotropism or hypoadrenocorticism, inborn errors of metabolism (ie, storage diseases and urea cycle disorders), infection or iatrogenic hypoglycemia were negative. An inappropriately high serum insulin level was noted in the face of marked hypoglycemia. The insulin:glucose ratio was 0.44 (<0.3) and the amended insulin:glucose ratio was 1268 (<30). Thoracic radiography and abdominal ultrasonography did not identify a cause for this elevated insulin level. Stabilization with a low, but adequate, blood glucose occurred with corticosteroid therapy, with further significant improvement with the addition of diazoxide. Peripheral neuropathy developed several months later, and concerns for quality of life led to humane euthanasia approximately 1 year after the initial diagnosis. Insulin levels remained high at the time of euthanasia. Necropsy found no gross lesions, though microscopic degeneration of the sciatic nerve and subjectively mildly increased size and number of pancreatic islets was noted. These findings were consistent with a diagnosis of congenital hyperinsulinism. Relevance and novel information: This is the first reported case of congenital hyperinsulinism in a cat and may parallel the diffuse form of hypoglycemic hyperinsulinism reported in humans and a single dog. It should be considered a differential diagnosis in kittens presenting for refractory hypoglycemia.

When a Histologic Diagnosis Becomes Factitious: A Case of Munchausen Syndrome.

Recurrent episodes of hypoglycemia are uncommon in non-diabetic patients. The workup investigation must confirm hypoglycemia and distinguish between endogenous versus exogenous hyperinsulinism. Simultaneous measurements of plasma glucose, insulin, C-peptide, and a screen for oral hypoglycemic agents should be performed. According to the results, further imaging studies may be necessary. A 43-year-old woman suffering from recurrent hypoglycemia presented to the emergency room (ER) with a hypoglycemic coma. She has had multiple episodes of documented hypoglycemia for the last 13 years. The case was initially investigated, and laboratory studies revealed endogenous hyperinsulinism. Screening for sulfonylureas, anti-insulin and anti-insulin receptor antibodies were negative. Body imaging and positron emission tomography (PET) with 68Ga-DOTANOC did not show evidence of an insulinoma. The patient was submitted to a pancreatectomy, which revealed nesidioblastosis in the histologic examination. Since then, the patient became hyperglycemic but the insulin doses were progressively reduced until new episodes of hypoglycemia recurred and the insulin was stopped. Again, inappropriately high levels of insulin were found at the time of hypoglycemic episodes. Computed tomography (CT) and PET scans did not find evidence of an insulinoma. A C-peptide was later found to be negative and insulin ampoules were found in her possession, making a diagnosis of a factitious disorder. Although rare, factious disorders are frequently overlooked and challenging to diagnose. Since they are very resource and time-consuming, self-inflicted illnesses should always be considered and ruled out beforehand.

Case report: A particularly rare case of endogenous hyperinsulinemic hypoglycemia complicated with pregnancy treated with short-acting somatostatin analog injections.

Hyperinsulinemic hypoglycemia is a rare disease, and only two cases complicated with pregnancy were published previously when our patient became pregnant. We introduce a successful management of a pregnancy in a patient with endogenous hyperinsulinemic hypoglycemia, a condition also known as non-insulinoma pancreatogenous hypoglycemia syndrome or formerly as nesidioblastosis. A 29-year-old female patient was treated with endogenous hyperinsulinemic hypoglycemia since the age of 4 months, taking daily 3 × 75 mg diazoxide, which adds up to 225 mg per day. Adequate glycemic control could be achieved with this therapy. Genetic testing and various imaging examinations were carried out earlier to specify the disease and to exclude focal forms. The patient came to the clinic with a positive pregnancy test and consequential hypoglycemic episodes. Hospital admission was needed to correct the metabolic condition. Although the patient was informed about the potential risks, she decided to carry out the pregnancy. According to the quite limited literature, somatostatin analogs are the only therapy used previously during pregnancy in hyperinsulinemic hypoglycemic patients. One publication reported normal pregnancy outcomes, but in another case, restricted fetal growth was observed. In our case, we stopped diazoxide and parallelly introduced short-acting somatostatin analog octreotide in the therapy, and further dietetic changes were proposed. In addition to daily regular self-blood glucose monitoring, regular gynecological controls were carried out monthly, and healthy fetal development was confirmed. The patient gave birth to her first child, a well-developed female neonate, in the 38th week, by a cesarean section.

[Mature teratoma of the anterior mediastinum with a predominance of the pancreatic component and signs of focal nesidioblastosis]. / Zrelaya teratoma perednego sredosteniya s preobladaniem pankreaticheskogo komponenta i priznakami fokal'nogo nezidioblastoza.

A case of a mature anterior mediastinal teratoma with a predominance of the pancreatic component (80% of the tumor) and signs of nesidioblastosis in a 46-year-old woman is presented. During histological examination, all components of the pancreatic parenchyma were determined - acini with interlobular and intralobular ducts, endocrine cells and islets of Langerhans of various sizes and shapes, as well as islet-duct complexes scattered in the acinar tissue. In addition to pancreatic tissue, cartilage, bronchial respiratory epithelium, small intestine tissue, hair follicles, and sebaceous glands were found in the neoplasm. Immunohistochemical examination revealed signs of focal nesidioblastosis. In the islets, insulin-positive ß-cells (80.0% of the volume of the islets), as well as endocrine cells expressing glucagon and somatostatin (10.0% of the volume of the islets) were determined. By 2020, only 4 such cases have been published in the English-language literature.

Diazoxide during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum: a case report.

Safety information on diazoxide for pregnant and lactating women with hypoglycemia is limited. In this case report, we assessed diazoxide concentrations in maternal and infant blood, cord blood, and breast milk. We described a 30-year-old pregnant woman diagnosed with hypoglycemia due to nesidioblastosis at 4 months of age. Before becoming pregnant, she was treated with oral diazoxide (75-375 mg). All medications were discontinued after she was discovered to be pregnant. During gestational week 25, diazoxide treatment was resumed at 150-175 mg daily for repeated hypoglycemic episodes. Diazoxide administration was continued in combination with diet treatment until delivery. Glucose levels were well controlled. During gestational week 40, a male infant weighing 3069 g was delivered via spontaneous vaginal delivery with no pregnancy or neonatal complications. Diazoxide concentrations detected in maternal serum at 2.5-11.6 h after oral treatment ranged from 12.4 to 32.7 µg/mL. In cord blood, the diazoxide concentration was 18.5 µg/mL at 7.2 h after the last dose. During lactation, no hypoglycemia or hyperglycemia was observed. The approximate calculated ratio of diazoxide in breast milk and maternal serum was 0.09. The calculated daily infant dose was 0.47 mg/kg/day. The relative infant dose via breast milk ranged from 3.1% to 5.9%. Diazoxide transferred from maternal blood to the fetus across the placenta. It also transferred into breast milk, but there were no harmful effects on the infant.

Hyperinsulinemic hypoglycemia in adolescents: case report and systematic review.

BACKGROUND: Hyperinsulinemic hypoglycemia is the most common cause of severe and persistent hypoglycemia in neonates and children. It is a heterogeneous condition with dysregulated insulin secretion, which persists in the presence of low blood glucose levels. CASE PRESENTATION: We report a case of a 15 year-old male with hyperinsulinemic hypoglycemia, who underwent a subtotal pancreatectomy after inadequate response to medical therapy. Pathological examination was positive for nesidioblastosis (diffuse ß-cell hyperplasia by H-E and immunohistochemical techniques). The patient's blood glucose levels normalized after surgery and he remains asymptomatic after 1 year of follow-up. The systematic review allowed us to identify 41 adolescents from a total of 205 cases reported in 22 manuscripts, from a total of 454 found in the original search done in PubMed and Lilacs. CONCLUSIONS: Although very well reported in children, hyperinsulinemic hypoglycemia can occur in adolescents or young adults, as it happens in our reported case. These patients can be seen, treated and reported by pediatricians or adult teams either way due to the wide age range used to define adolescence. Most of them do not respond to medical treatment, and subtotal distal pancreatectomy has become the elected procedure with excellent long-term response in the vast majority.

Adult-Onset Focal Nesidioblastosis With Nodular Formation Mimicking Insulinoma.

Nesidioblastosis is defined as the neoformation of the islets of Langerhans from the pancreatic ductal epithelium and is recognized as the most common cause of hyperinsulinemic hypoglycemia in infants. We herein report an extremely rare case of adult-onset focal nesidioblastosis with the unusual feature of hyperplastic nodular formation. A 55-year-old woman was admitted to our hospital for a tumor detected in the body of the pancreas by magnetic resonance imaging screening. Laboratory examinations showed a high insulin level in the blood. Contrast-enhanced computed tomography and the selective arterial calcium injection test suggested the presence of multiple insulinomas in the body and tail of the pancreas, and, thus, the patient underwent distal pancreatectomy. A histopathological examination of the tumor in the body of the pancreas showed the nodular hyperplasia of islet-like cell clusters. In addition, many small intralobular ductules and islet cells appeared to be budding from the proliferating ductal epithelium, forming "ductuloinsular complexes". No other abnormal lesion was detected in the remainder of the pancreas. The histopathological diagnosis was focal nesidioblastosis. The patient has remained free of the recurrence of hypoglycemic episodes for more than 31 months. The present case of rare adult-onset focal nesidioblastosis with hyperplastic nodular formation was preoperatively identified as an apparent pancreatic tumor mimicking insulinoma. Nesidioblastosis and insulinoma need to be considered in cases of hyperinsulinemic hypoglycemia, even in adult patients.