Diagnosis: Insulinoma
This 12-year-old has an insulinoma until proven otherwise, given the classic triad of fasting hypoglycemia (glucose 20-30 mg/dL), inappropriately elevated insulin levels during hypoglycemia, and elevated liver enzymes suggesting hepatic glycogen depletion from chronic hyperinsulinism. 1, 2
Diagnostic Confirmation Required
The diagnosis hinges on documenting Whipple's triad during a supervised fast:
- Perform a 72-hour supervised fast with serial measurements of glucose, insulin, C-peptide, and proinsulin 1, 2
- Diagnostic criteria during hypoglycemia (glucose <55 mg/dL):
Critical pitfall: Some insulinomas present atypically with normal fasting tests but glucose-stimulated hypoglycemia 3, 4, 5. If the 72-hour fast is negative but clinical suspicion remains high:
- Perform an oral glucose tolerance test (OGTT) looking for paradoxical hyperinsulinemia followed by reactive hypoglycemia 1-3 hours post-glucose 3, 4, 6
- Consider glucagon stimulation test (1 mg IV), measuring insulin response—exaggerated insulin secretion with subsequent hypoglycemia suggests insulinoma 5
Essential Additional Testing
- Measure urinary sulfonylurea to exclude factitious hypoglycemia 1
- Screen for MEN-1 syndrome given her age (family history, calcium, PTH, prolactin) 1
- Hepatic imaging is mandatory even before localization studies, as elevated transaminases may indicate hepatic adenomas or other pathology 7
Tumor Localization
Once biochemical diagnosis is confirmed:
- Endoscopic ultrasound (EUS) is first-line, localizing ~82% of insulinomas 1
- Multiphasic CT or MRI of pancreas to assess for metastatic disease 1
- Octreoscan has limited utility for insulinomas (less octreotide-avid than other neuroendocrine tumors) and should only be performed if octreotide therapy is being considered 1
- Selective arterial calcium stimulation (Imamura-Doppman procedure) reserved for cases where other localization is negative or for recurrent disease 1
Immediate Management
Preoperative stabilization is essential:
- Frequent small meals with complex carbohydrates to prevent fasting hypoglycemia 1
- Diazoxide is first-line medical therapy to stabilize glucose (inhibits insulin secretion) 1
- Acarbose may help by slowing carbohydrate absorption 1
- AVOID octreotide unless tumor is proven Octreoscan-positive, as it can paradoxically worsen hypoglycemia in insulinomas lacking somatostatin receptors 1
- Prescribe glucagon emergency kit and train family members on administration for severe hypoglycemic episodes 1, 8
- Continuous glucose monitoring (CGM) should be implemented immediately to detect nocturnal hypoglycemia and guide treatment adjustments 1
Definitive Treatment
Surgical resection is curative in 90% of cases and should be pursued once localized 1, 2:
- Enucleation for small, superficial tumors
- Partial pancreatectomy for larger or deeper lesions
- 90% of insulinomas are benign and solitary 1
Differential Diagnosis to Exclude
While insulinoma is most likely, briefly consider:
- Glycogen storage disease (GSD): Would present with hepatomegaly from birth/early childhood, not at age 12 with new-onset symptoms; ketones would be present during hypoglycemia in GSD III/VI/IX (absent in hyperinsulinism) 7, 9
- Post-bariatric hypoglycemia: Not applicable—no surgical history 1
- Autoimmune hypoglycemia: Rare; check insulin antibodies if C-peptide/insulin relationship is discordant 10
- Exogenous insulin administration: Excluded by elevated C-peptide 2
The variability in morning glucose levels (some normal, some critically low) is consistent with insulinoma's episodic autonomous insulin secretion, particularly triggered by fasting states. 1, 3