title: Clinical presentation in insulinoma predicts histopathological tumour characteristics.
abstract: BACKGROUND
  Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72-h fast. However, the prognostic value of parameters in the standardized 72-h fast on histopathological tumour criteria and clinical presentation has not been examined.
  
  
  METHODS
  In thirty-three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki-67 index. Cut-off values for classical grading (G(clas)) were set at G1(clas) ≤ 2%, G2(clas) 3-20% & G3(clas) >20% and for modified grading (G(mod)) at G1(mod) <5%, G2(mod) 5-20% & G3(mod) >20%.
  
  
  RESULTS
  When G(mod) criteria were applied, the initial blood glucose was lower in GII/III(mod) patients compared to GI(mod) (2.8 ± 0.8 vs 3.8 ± 1.3 mmol/l; P = 0.046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0.001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0.001) and c-peptide (basal c-peptide 5.4 ± 2.4 vs 2.7 ± 1.6 μg/l; P = 0.004; end of fast c-peptide 5.3 ± 2.4 vs 2.5 ± 1.4 μg/l; P = 0.001) were significantly higher in GII/III(mod) than in GI(mod). No differences between the groups were observed when G(clas) criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki-67 index and tumour size.
  
  
  CONCLUSIONS
  This study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72-h fast. Lower initial blood glucose levels and higher concentrations of insulin and c-peptide are associated with worse tumour grading and larger tumour size.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Wolf
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Yvonne
authors: Y
authors: Winhofer
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Sabina
authors: S
authors: Smajis
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy.|Medical Direction, Specialized Hospital Complex Agathenhof, Micheldorf, Austria.
authors: Christian-Heinz
authors: CH
authors: Anderwald
authors: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors: Christian
authors: C
authors: Scheuba
authors: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors: Bruno
authors: B
authors: Niederle
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Alois
authors: A
authors: Gessl
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Anton
authors: A
authors: Luger
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Krebs
authors: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors: Oskar
authors: O
authors: Koperek
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D015331:Cohort Studies; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007003:Hypoglycemia / Q000097:blood; D007328:Insulin / Q000097:blood*; D007340:Insulinoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology*; D012189:Retrospective Studies; D047368:Tumor Burden
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin