hypoglycemia

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: Hypoglycemia: case based case based 1. Diagnostic approach to hypoglycemia 2. Iatrogenic hypoglycemia 3. Tumor-associated hypoglycemia Case 1 Case 1  18 year old male  Prior ADHD, school suspension-fighting  LOC, SZ, CBG 1.8 mM  Stepfather T2DM: glyburide  Grandfather T2DM: insulin Hypoglycemia: Symptoms 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 Response to Hypoglycemia Response to Hypoglycemia Blood Glucose Symptoms < 3.3 mM Sweating, tremor, anxiety, palpitations, hunger 2.8 – 3.1 mM Early cognitive dysfn. (confusion, mood changes) 2.5 – 2.8 mM Lethargy, obtundation < 1.7 mM Coma < 1.1 mM Convulsions …Death Response to Hypoglycemia Response to Hypoglycemia Blood Glucose Hormonal response < 4.4 mM Insulin ↓ to low levels 3.6 - 3.9 mM Glucagon & catecholamines < 3.3 mM Growth Hormone & cortisol < 2.5 mM Pancreas: no insulin release Hypoglycemic Disorders Hypoglycemic Disorders  Fasting vs. Post-prandial  Appearance: healthy vs. sick  Hyper-insulinemic vs. Hypo-insulinemic Post-prandial Hypoglycemia 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 Post-prandial Hypoglycemia Post-prandial Hypoglycemia Neuroglycopenic symptoms:  Unripe ackee fruit  Bariatric surgery?  Insulinoma, islet hypertrophy  Non-insulinoma pancreatogenous hypoglycemia (NIPHS) [...]...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 Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT Fasting Hypoglycemia 75g glucose,...  Glucagon 1mg IV  ↑ BS > 1.4 mM at 30 min βHβ < 2.7 mM (serum ketones) Whipple’s Triad Koch’s postulates of Hypoglycemia Symptoms  BS < 2.8 mM  Resolution of symptoms with CHO  Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT Fasting Hypoglycemia 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars FPG >2.8 mM 72h fast BG < 2.8... Glucose rise < 1.4 mM   No further episodes LOC/SZ/low BS   D/C home without any imaging Advised to avoid insulin, OHA Final Diagnosis: surreptitious use insulin +/- OHA Hypoglycemia: Family Hx of DM? Access to insulin?  Access to oral hypoglycemia agents?  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... 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 Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT Fasting Hypoglycemia 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars FPG >2.8 mM 72h fast BG < 2.8 mM? NO •Vigorous exercise •Glucagon... of early AM spells, relieved with snacks/O.J., weight gain > 100 lbs  Case 3 BS 1.8 mM  Insulin 155 pM  C-peptide 1.9 nM  Pro-insulin 133 pM  Hypoglycemia Symptoms after fasting or skipped meals? Symptoms (only adrenergic) after eating? OGTT Fasting Hypoglycemia 75g glucose, BS q30min x 5h BS < 2.8 mM? If yes: avoid refined sugars FPG >2.8 mM 72h fast BG < 2.8 mM? NO •Vigorous exercise •Glucagon... pM) Insulin/glucose > 0.3 Proinsulin: < 5 pM < 10-20% Anti-insulin Ab’s 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  Case 3 49M, Fall 2002: LBP & abdominal mass  Retroperitoneal seminoma  Chemotherapy:    Etoposide, Cisplatinum,... •Secretes IGFIOHA screen – OHA screen + BP inhibitor Surreptitious Insulin YES Prosinsulin: > 5 pM > 10-20% > 3 uU/mL (21.5 pM) Insulin/glucose > 0.3 Proinsulin: < 5 pM < 10-20% Anti-insulin Ab’s 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 . Hospital www.drharper.ca Hypoglycemia: Hypoglycemia: case based case based 1. Diagnostic approach to hypoglycemia 2. Iatrogenic hypoglycemia 3. Tumor-associated hypoglycemia Case 1 Case. Post-prandial Hypoglycemia Post-prandial Hypoglycemia Neuroglycopenic symptoms:  Unripe ackee fruit  Bariatric surgery?  Insulinoma, islet hypertrophy  Non-insulinoma pancreatogenous hypoglycemia. hypertrophy  Non-insulinoma pancreatogenous hypoglycemia (NIPHS) Post-prandial Hypoglycemia Post-prandial Hypoglycemia  Non-insulinoma pancreatogenous hypoglycemia (NIPHS)  Adult nesidioblastosis (islet hypertrophy)  Postprandial