Insulinoma

Incidence and Presentation

Most common functioning PNET
- Average age at diagnosis 45, often have years of symptoms prior to diagnosis
Symptoms vary, get Whipple’s Triad
- Fasting hypoglycaemia (<50 mg/dL or <2.7 mmol/L)
- Symptoms of hypoglycaemia
- Immediate relief of symptoms after the administration of intravenous glucose
Distributed evenly throughout pancreas, despite β cells being more in body/tail
Rarely can also be in Duodenum, Splenic hilum, Gastrocolic ligament
Most tumours small (1-1.5cm), benign (> 90%) and solitary
Most sporadic, 5% associated with MEN 1

Rare syndrome
Characterized by endogenous hyperinsulinaemic hypoglycaemia that is not caused by an insulinoma
Pancreas shows
- Beta cell hypertrophy
- Islets with enlarged and hyperchromatic nuclei
- Increased islets budding from periductular epithelium
In patients that fail to find an insulinoma on localisation studies a selective arterial calcium stimulation test with hepatic venous sampling should be performed to establish the hyperinsulinemia is of pancreatic origin
Treatment - low carb diet, Acarbose, Graded pancreatectomy

History
- Timing of symptoms related to meals
- Medications taken by patient and family
- Family and social history
Diagnosis requires
- Inappropriate high serum insulin levels during an episode of hypoglycaemia
Bloods
- If spontaneous episode, measure
  - Plasma glucose, insulin, C-peptide, proinsulin and beta-hydroxybutyrate
- Gold standard test – 72hr monitored fast

Glucose
- Document timing of hypoglycaemia and symptoms
Insulin
- Will be high if insulinoma (and other causes)
Can measure insulin antibodies or insulin receptor antibodies
- To R/O Insulin autoimmune hypoglycaemia
C-peptide
- Breakdown product of insulin production
- Will be high in insulinoma, low if exogenous administration
Proinsulin
- Precursor for insulin
- Will be high in insulinoma, low if exogenous administration
Beta-hydroxybutyrate
- Insulin is antiketogenic, levels will be low if insulinoma
72 Hour Monitored Fast
- Calorie free, caffeine free beverages only
- Blood samples every 6 hours, then more frequently
- Fast stopped at 72hrs or when BSL < 3.1 or symptomatic, bloods taken again at this stage
- Test should show a inappropriately elevated insulin in the setting of hypoglycaemia

Same as general Pancreatic neuroendocrine neoplasms localisation principles
- Except SRS/DOTATE PET less indicated in insulinomas as they rarely express somatostatin receptors (still usually done however)
If not located pre-op
- Blind exploration with IO USS
- Careful palpation of entire pancreas and duodenum
- Completely mobilise pancreas
- If cannot be localised, biopsy pancreas tail for Non-insulinoma Pancreatogenous Hypoglycaemia Syndrome

Mainstay: Surgical resection, only cure
- Pre-op glycaemic control
  - Glucose infusions
  - Diazoxide (decreases beta cell insulin release)
Enucleation preferred surgery
- 90% are benign
- Contraindication:
  - 2cm in size
  - < 2mm from the main pancreatic duct
Anatomic resection may be necessary

Isolated liver disease can be resected alongside the primary tumour
- Although typically not curable the slow growing nature of the tumor means good life expectancy
Tumour debulking in metastatic disease may give biochemical cure
Chemotherapy (Streptozocin + Doxorubicin)
- Median survival with metastatic disease is 5yrs

Life expectancy normal after complete excision of benign insulinoma
Persistent high insulin can be managed with
- Somatostatin analogues
- Hepatic artery embolisation
- Diazoxide