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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.

Abstract 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 (

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 β-cells," has potential diagnostic value. [ABSTRACT FROM AUTHOR]

Nesidioblastoma and nesidioblastosis were terms given to neoplastic and nonneoplastic 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. [ABSTRACT FROM AUTHOR]

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.

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 β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 β-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.

The obesity epidemic has led to the growing number of bariatric operations and the expansion of indications for this operation as the most effective method of treatment, that’s why endocrinologists are increasingly faced the challenge of late complications, including postbariatric hypoglycemia. Postbariatric hypoglycemia is a rare but severe metabolic disorder that occurs months or years after upper gastrointestinal surgery. Postbariatric hypoglycemia can be accompanied by severe clinical symptoms and lead to disability and decreasing of the life’s quality. It is difficult to assess the prevalence of hypoglycemia after bariatric surgery due to the lack of clear diagnostic criteria, often a hidden clinical picture and ignorance of doctors and patients about this complication. Hypoglycemia in this case has postprandial and hyperinsulinemic nature. The mechanisms of development of this complication have recently been actively discussed. The exchange of incretins and dysregulation of insulin secretion are the subject of constant research in this area. Understanding the mechanisms of development of this condition makes it possible to develop optimal methods of diagnosis and treatment. The issues of pathophysiology, basic principles of diagnosis and treatment of post-bariatric hypoglycemia will be considered in this review.

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 x 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. [ABSTRACT FROM AUTHOR]