What is nesidioblastosis and how is it managed?

Nesidioblastosis: Definition, Diagnosis, and Management

Nesidioblastosis is a rare condition characterized by diffuse proliferation of pancreatic islet cells budding from ductal epithelium, causing hyperinsulinemic hypoglycemia that requires medical management with diazoxide as first-line therapy or surgical intervention in refractory cases. 1

Definition and Epidemiology

• Nesidioblastosis was first described by Laidlaw in 1938 as diffuse proliferation of pancreatic islet cells budding from ductal epithelium 1
• While primarily recognized as the main cause of persistent hyperinsulinemic hypoglycemia in infants, it is a very rare entity in adults, representing only 0.5-5% of cases of organic hyperinsulinemia 1
• In adults, insulinoma accounts for most cases of hyperinsulinemic hypoglycemia, with nesidioblastosis being much less common 2

Clinical Presentation

• Patients present with symptoms of hypoglycemia, including:
  • Recurrent or chronic hypoglycemic episodes 3
  • Neurological manifestations (altered consciousness, seizures) 3
  • Patients are often misdiagnosed with epilepsy due to seizures and loss of consciousness 3
• Delayed diagnosis can lead to irreversible damage to the central nervous system 3
• Clinical features are often identical to those of insulinoma, making differentiation challenging 2

Diagnostic Approach

• Laboratory findings typically show:

  • Low blood glucose levels 3
  • Insulin levels that are inappropriate for the degree of hypoglycemia (though often within normal range) 3
  • Normal proinsulin-like component of circulating immunoreactive insulin (unlike insulinoma) 2

• Diagnostic criteria include:

  • Supervised fasting test showing inappropriately high insulin and C-peptide levels 4
  • Low free fatty acid and ketone body concentrations 4
  • Glycemic response to glucagon 4
  • Absence of ketonuria 4

• Imaging studies have limited utility:

  • Conventional imaging (ultrasound, CT, MRI) typically fails to identify lesions 3
  • Somatostatin receptor scintigraphy may show diffuse uptake in severe cases 3
  • GLP-1 analog scintigraphy may detect focal uptake in some cases 3

• When imaging fails to identify a tumor, more invasive techniques may be necessary:

  • Selective arterial calcium stimulation testing for gradient-guided surgery in adults 4
  • Percutaneous transhepatic pancreatic venous sampling in neonates 4

Histopathology

• Histopathologic criteria for nesidioblastosis include:
  • Hypertrophic islets with beta cells showing pleomorphic nuclei 4
  • Ductuloinsular complexes 4
  • Neoformation of islets from ducts 4
  • Can present as diffuse or focal forms 4
  • Positive immunohistochemical staining for insulin 3

Management

Medical Management

• Diazoxide is the first-line pharmacological treatment:

  • FDA-approved for management of hypoglycemia due to hyperinsulinism in adults with inoperable islet cell adenoma/carcinoma and in children with nesidioblastosis 5
  • Should be used after definitive diagnosis is established 5
  • May be used preoperatively as a temporary measure and postoperatively if hypoglycemia persists 5

• GLP-1 receptor antagonists:

  • Exendin 9-39 has shown promise in correcting hypoglycemia in similar conditions (post-gastric bypass hypoglycemia) 6
  • This approach is consistent with the role of GLP-1 in postprandial hypoglycemia 6
  • However, evidence is still limited as these pharmacologic interventions have only been evaluated in small studies 6

Surgical Management

• Surgical intervention is indicated when medical therapy fails to control hypoglycemia 2

• The extent of pancreatic resection is challenging to determine:

  • Limited resection may not relieve symptoms 7
  • Extensive resection (>90%) may lead to insulin dependency and permanent diabetes 2
  • In adults, resection of up to 90% of the pancreas has relieved symptoms in some patients 7
  • In focal forms, partial pancreatectomy may be sufficient 4
  • In diffuse forms, 95% pancreatectomy may be necessary, especially in neonates 4

• Outcomes of surgical intervention:

  • Success rates vary, with approximately 50% of patients achieving symptom relief after extensive resection 7
  • There is a delicate balance between successful treatment, persistence of disease, and pancreatic endocrine insufficiency 7

Special Considerations

• Nesidioblastosis has been associated with post-Roux-en-Y gastric bypass hypoglycemia, though this connection remains controversial 6
• Some studies suggest that the development of hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover 6
• Continuous glucose monitoring (CGM) is an important tool for individuals at risk of severe hypoglycemia due to nesidioblastosis 6
• Conservative management approaches should be pursued before attempting surgical intervention 6

Pitfalls and Challenges

• Misdiagnosis is common due to similarity with other causes of hypoglycemia, particularly insulinoma 2
• Conventional imaging techniques (US, CT, MRI) are often ineffective for diagnosis 3
• The extent of surgical resection is difficult to determine, with a fine line between under-treatment and causing diabetes 7
• Delayed diagnosis can lead to irreversible neurological damage 3
• Even after extensive pancreatic resection, hypoglycemia may recur, suggesting the possibility of coexisting insulinoma 3