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Non-Diabetic Hypoglycemia

Non-Diabetic Hypoglycemia. Medical Grand Rounds May 14, 2004 Dr. William Harper Assistant Professor of Medicine, McMaster University. Endocrinologist, Hamilton General Hospital www.drharper.ca. Hypoglycemia: case based. Diagnostic approach to hypoglycemia Iatrogenic hypoglycemia

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Non-Diabetic Hypoglycemia

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  1. Non-Diabetic Hypoglycemia Medical Grand Rounds May 14, 2004 Dr. William Harper Assistant Professor of Medicine, McMaster University. Endocrinologist, Hamilton General Hospital www.drharper.ca

  2. Hypoglycemia: case based • Diagnostic approach to hypoglycemia • Iatrogenic hypoglycemia • Tumor-associated hypoglycemia

  3. Case 1 • 18 year old male • Prior ADHD, school suspension-fighting • LOC, SZ, CBG 1.8 mM • Stepfather T2DM: glyburide • Grandfather T2DM: insulin

  4. Hypoglycemia: Symptoms • Sympathoadrenal: • diaphoresis, warmth, anxiety, tremor, nausea, hunger, palpitations/tachycardia • Neuroglycopenic: • Fatigue, dizziness, H/A, visual disturbance, drowsiness, difficulty speaking, inability to concentrate, amnesia, abnormal behaviour, mood changes, loss of consciousness, seizure, focal neurological deficit

  5. Response to Hypoglycemia

  6. Response to Hypoglycemia

  7. Hypoglycemic Disorders • Fasting vs. Post-prandial • Appearance: healthy vs. sick • Hyper-insulinemic vs. Hypo-insulinemic

  8. Post-prandial Hypoglycemia Sympathoadrenal symptoms only: • 2° to refined sugars/simple CHO • Alimentary Surgery (gastrectomy, etc) • Dumping syndrome  fluid shifts • Dysglycemia • IFG, IGT, Early Type 2 DM • 4-5h after

  9. Post-prandial Hypoglycemia Neuroglycopenic symptoms: • Unripe ackee fruit • Bariatric surgery? • Insulinoma, islet hypertrophy • Non-insulinoma pancreatogenous hypoglycemia (NIPHS)

  10. Post-prandial Hypoglycemia • Non-insulinoma pancreatogenous hypoglycemia (NIPHS) • Adult nesidioblastosis (islet hypertrophy) • Postprandial severe neuroglycopenia • 72h fast negative • Rare, M > F (insulinoma F > M) • Ca+ stimulation test • Rx: partial pancreatectomy

  11. Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars Fasting Hypoglycemia FPG >2.8 mM < 2.8 mM Insulin YES < 3 uU/mL (21.5 pM) Insulin/glucose < 0.3 > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 72h fast • AI, hypothyroid • Liver Disease, EtOH • Enzyme defects • Severe, protracted malnutrition • Non-islet cell tumor • Secretes IGF-II • Secretes IGFI-BP inhibitor BG < 2.8 mM? C-peptide NO > 0.2 nM < 0.2 nM • Vigorous exercise • Glucagon stimulation • (rise BS > 1.4 mM) • Insulinoma • OHA screen – • Prosinsulin: • > 5 pM • > 10-20% OHA OHA screen + Proinsulin: < 5 pM < 10-20% Surreptitious Insulin Anti-insulin Ab’s

  12. Case 1 • 18 year old male • Prior ADHD, school suspension-fighting • LOC, SZ, CBG 1.8 mM • No critical BW drawn • Stepfather T2DM: glyburide • Grandfather T2DM: insulin

  13. Critical Blood Work • Prior to treatment send venous BW: • Venous BS • Insulin, c-peptide, +/- pro-insulin • ACTH, cortisol

  14. Criteria: Endogenous hyperinsulinemia • BS < 2.8 mM and… • Insulin > 21.5 pM • C-peptide > 0.2 nM • Proinsulin > 5 pM • Insulin surrogates: • Glucagon 1mg IV   BS > 1.4 mM at 30 min • H < 2.7 mM (serum ketones)

  15. Whipple’s TriadKoch’s postulates of Hypoglycemia • Symptoms • BS < 2.8 mM • Resolution of symptoms with CHO

  16. Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars Fasting Hypoglycemia FPG >2.8 mM < 2.8 mM Insulin YES < 3 uU/mL (21.5 pM) Insulin/glucose < 0.3 > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 72h fast • AI, hypothyroid • Liver Disease, EtOH • Enzyme defects • Severe, protracted malnutrition • Non-islet cell tumor • Secretes IGF-II • Secretes IGFI-BP inhibitor BG < 2.8 mM? C-peptide NO > 0.2 nM < 0.2 nM • Vigorous exercise • Glucagon stimulation • (rise BS > 1.4 mM) • Insulinoma • OHA screen – • Prosinsulin: • > 5 pM • > 10-20% OHA OHA screen + Proinsulin: < 5 pM < 10-20% Surreptitious Insulin Anti-insulin Ab’s

  17. Case 1 • Serum screen negative for OHA x 2 • Admit 72h fast: • Lowest CBG 4.1 mM, VBG 3.9 mM • Serum ketones trace during fast • End of fast: • 1 mg IV glucagon • Glucose rise < 1.4 mM • D/C home without any imaging • No further episodes LOC/SZ/low BS • Advised to avoid insulin, OHA • Final Diagnosis: surreptitious use insulin +/- OHA

  18. Hypoglycemia: Family Hx of DM? • Access to insulin? • Access to oral hypoglycemia agents?

  19. Case 2 • 71M, admit with ascites • Known cirrhotic 2° EtOH, abstinate x 7y • BS 6-8 mM in-hospital until day 14 • Awoke with BS 3.4 mM • BS 2.0-2.9 despite + + po CHO intake • Next day BS 1.5-1.9 mM • D10W IV gtt @ 100-150/h x 2-3d

  20. Case 2 • Meds: amiodarone, altace, ASA, lasix, aldactone, cipro, ativan qhs PRN • AST, ALT, GGT mildly elevated • Albumin 39, INR 1.2 • Critical BW: • Venous BS 1.5 mM • Insulin 317 pM, C-peptide 4.0 nM • ACTH 7 pM, cortisol 751 nM

  21. Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars Fasting Hypoglycemia FPG >2.8 mM < 2.8 mM Insulin YES < 3 uU/mL (21.5 pM) Insulin/glucose < 0.3 > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 72h fast • AI, hypothyroid • Liver Disease, EtOH • Enzyme defects • Severe, protracted malnutrition • Non-islet cell tumor • Secretes IGF-II • Secretes IGFI-BP inhibitor BG < 2.8 mM? C-peptide NO > 0.2 nM < 0.2 nM • Vigorous exercise • Glucagon stimulation • (rise BS > 1.4 mM) • Insulinoma • OHA screen – • Prosinsulin: • > 5 pM • > 10-20% OHA OHA screen + Proinsulin: < 5 pM < 10-20% Surreptitious Insulin Anti-insulin Ab’s

  22. Case 2 • Serum glyburide: • Oct 22, 2003: 60 nM • Oct 23, 2003: 66 nM (Patient not prescribed glyburide) • Diagnosis: iatrogenic hypoglycemia 2° to dispensing error • Treatment: P&T committee  review OHA stock drawer policy

  23. Case 3 • 49M, Fall 2002: LBP & abdominal mass • Retroperitoneal seminoma • Chemotherapy: • Etoposide, Cisplatinum, Bleomycin • Tumor: good response

  24. Case 3 • Chemo  anorexia • Spells of bizzare behaviour, confusion, lethargy • Random BS 3.6 mM, HbA1c 3.4% • PHx: 10y of early AM spells, relieved with snacks/O.J., weight gain > 100 lbs.

  25. Case 3 • BS 1.8 mM • Insulin 155 pM • C-peptide 1.9 nM • Pro-insulin 133 pM

  26. Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars Fasting Hypoglycemia FPG >2.8 mM < 2.8 mM Insulin YES < 3 uU/mL (21.5 pM) Insulin/glucose < 0.3 > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 72h fast • AI, hypothyroid • Liver Disease, EtOH • Enzyme defects • Severe, protracted malnutrition • Non-islet cell tumor • Secretes IGF-II • Secretes IGFI-BP inhibitor BG < 2.8 mM? C-peptide NO > 0.2 nM < 0.2 nM • Vigorous exercise • Glucagon stimulation • (rise BS > 1.4 mM) • Insulinoma • OHA screen – • Prosinsulin: • > 5 pM • > 10-20% OHA OHA screen + Proinsulin: < 5 pM < 10-20% Surreptitious Insulin Anti-insulin Ab’s

  27. Case 3 • Hypoglycemia treated with: • Diazoxide • Prednisone (bleomycin lung toxicity) • ICC of retroperitoneal tumor negative for insulin • CT scan: bulky pancreatic tail • Octreoscan: negative • MRI: tumor in tail of pancreas

  28. Case 3 • Intraoperative U/S: single tumor confirmed at tail of pancreas  resected • Postop: no further spells, weight loss • MOT contacted for license resinstatement

  29. Insulinoma • Rare neuroendocrine tumor of pancreas • 4 cases/million person-years • Originating outside pancreas: 1-2 cases reports only (cervical cancer) • 59% female • Most (80-90%) benign • Sporadic or part of MEN-1

  30. Insulinoma • Diagnosis: • Biochemical • Localization: • CT Scan • Octreoscan (60% Sen) • Intraop U/S – most sensitive test • Selective arterial Ca2+ stimulation

  31. Insulinoma

  32. Insulinoma • Treatment: • Surgical resection • Diazoxide • Octreotide • Inteferon alpha • Malignant: • Octreotide-idium 111 • Chemo: streptozozin, doxorubicin

  33. Case 4 • 57M, well until Oct 2003 • Transient spells: drowsiness, vertigo or dysequilibrium • No relationship with food • Florida over the winter… • Mar 5, 04: felt drunk despite no EtOH, went to sleep early, next AM was unable to be aroused

  34. Case 4 • Taken to Florida ER, given IV glucose, d/c from ER, told to “eat more” • Next AM: unable to be aroused • EMS called again, this time admitted • BS 1.8 mM • Insulin 20 pM, C-peptide 3.1 nM • CT scan: large retroperitoneal mass contiguous with pancreas • Octreoscan positive…

  35. Case 4 • Inoperable • TPN/D5W, high CHO diet as tolerated • Diazoxide, Octreotide • Hepatic artery embolization • Octreotide-indium 111 ?

  36. Hypoglycemia: case based • Diagnostic approach to hypoglycemia • Iatrogenic hypoglycemia • Tumor-associated hypoglycemia

  37. Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars Fasting Hypoglycemia FPG >2.8 mM < 2.8 mM Insulin YES < 3 uU/mL (21.5 pM) Insulin/glucose < 0.3 > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 72h fast • AI, hypothyroid • Liver Disease, EtOH • Enzyme defects • Severe, protracted malnutrition • Non-islet cell tumor • Secretes IGF-II • Secretes IGFI-BP inhibitor BG < 2.8 mM? C-peptide NO > 0.2 nM < 0.2 nM • Vigorous exercise • Glucagon stimulation • (rise BS > 1.4 mM) • Insulinoma • OHA screen – • Prosinsulin: • > 5 pM • > 10-20% OHA OHA screen + Proinsulin: < 5 pM < 10-20% Surreptitious Insulin Anti-insulin Ab’s

  38. Criteria: Endogenous hyperinsulinemia • BS < 2.8 mM and… • Insulin > 21.5 pM • C-peptide > 0.2 nM • Proinsulin > 5 pM • Insulin surrogates: • Glucagon 1mg IV   BS > 1.4 mM at 30 min • H < 2.7 mM (serum ketones)

  39. END

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