Adult-onset nesidioblastosis is an exceedingly rare yet significant cause of persistent hyperinsulinemic hypoglycemia. This condition is often associated to bariatric surgeries such as Roux-en-Y gastric bypass and sleeve gastrectomy. Characterized by abnormal β-cell hyperplasia and hypertrophy, its diagnosis presents a unique challenge due to overlapping features with insulinomas and post-bariatric hypoglycemia syndrome (PBHS). We report a 55-year-old woman with a history of gastric sleeve and Roux-en-Y gastric bypass surgeries who presented with a 1.5-year history of recurrent hypoglycemic episodes. Her symptoms, including blurred vision, tremors, and altered consciousness, persisted despite medical therapy with octreotide, acarbose, and nifedipine. Extensive imaging, including magnetic resonance imaging and endoscopic ultrasound, ruled out insulinomas, raising suspicion of non-insulinoma pancreatogenous hypoglycemia syndrome. The patient underwent laparoscopic subtotal distal pancreatectomy with spleen preservation. Histopathological examination confirmed nesidioblastosis, revealing irregular islet distribution and β-cell hypertrophy. Post-surgery, the patient achieved normoglycemia without recurrence of hypoglycemic episodes during follow-up. This case highlights the complexity of diagnosing nesidioblastosis in adults, especially following bariatric surgeries. Nesidioblastosis involves β-cell hyperplasia and hypertrophy driven by hormonal factors like GLP-1, whereas PBHS results from altered incretin patterns causing excessive insulin release. Advanced imaging and multidisciplinary collaboration are important for accurate diagnosis. Surgical management remains a cornerstone for refractory cases, as demonstrated in this patient's remarkable recovery. Nesidioblastosis is a rare condition but should be considered in the differential diagnosis of post-bariatric surgery hypoglycemia. This case highlights the importance of distinguishing nesidioblastosis from PBHS to ensure appropriate and effective management strategies.

Hypoglycaemia is a medical emergency requiring an immediate intervention to prevent neuroglycopenic symptoms such as confusion, seizures, and coma. While evaluating for the cause of hypoglycemia, after excluding common causes like insulin use or sepsis, other causes involving endogenous hypoglycemia need to be evaluated. A cause to be considered is nesidioblastosis. This rare entity is also known as non-insulinoma pancreatogenous hypoglycemia syndrome. There have been instances where this disorder has been mistaken as insulinoma due to the characteristics shared by the two. Here, we present a case of a non-diabetic male experiencing symptoms of giddiness and palpitations for the past two years who had been extensively evaluated to rule out insulinoma and was diagnosed with nesidioblastosis.

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.

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.