hypoglycemia
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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:
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
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 (only adrenergic) after eating?
Symptoms after fasting
or skipped meals?
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
72h fast
BG < 2.8 mM?
•
Vigorous
exercise
•
Glucagon
stimulation
(rise BS > 1.4 mM)
YES
NO
Insulin
> 3 uU/mL (21.5 pM)
Insulin/glucose > 0.3
< 3 uU/mL (21.5 pM)
Insulin/glucose < 0.3
C-peptide
> 0.2 nM
< 0.2 nM
Insulinoma
OHA screen –
Prosinsulin:
> 5 pM
> 10-20%
OHA
OHA screen +
Proinsulin:
< 5 pM
< 10-20%
Surreptitious Insulin
Anti-insulin Ab’s
•
AI, hypothyroid
•
Liver Disease, EtOH
•
Enzyme defects
•
Severe, protracted
malnutrition
•
Non-islet cell tumor
•
Secretes IGF-II
•
Secretes IGFI-
BP inhibitor
Case 1
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
Critical Blood Work
Critical Blood Work
Prior to treatment send venous BW:
Venous BS
Insulin, c-peptide, +/- pro-insulin
ACTH, cortisol
Criteria: Endogenous
Criteria: Endogenous
hyperinsulinemia
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
βHβ < 2.7 mM (serum ketones)
Whipple’s Triad
Whipple’s Triad
Koch’s postulates of Hypoglycemia
Koch’s postulates of Hypoglycemia
Symptoms
BS < 2.8 mM
Resolution of symptoms with CHO
Hypoglycemia
Symptoms (only adrenergic) after eating?
Symptoms after fasting
or skipped meals?
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
72h fast
BG < 2.8 mM?
•
Vigorous
exercise
•
Glucagon
stimulation
(rise BS > 1.4 mM)
YES
NO
Insulin
> 3 uU/mL (21.5 pM)
Insulin/glucose > 0.3
< 3 uU/mL (21.5 pM)
Insulin/glucose < 0.3
C-peptide
> 0.2 nM
< 0.2 nM
Insulinoma
OHA screen –
Prosinsulin:
> 5 pM
> 10-20%
OHA
OHA screen +
Proinsulin:
< 5 pM
< 10-20%
Surreptitious Insulin
Anti-insulin Ab’s
•
AI, hypothyroid
•
Liver Disease, EtOH
•
Enzyme defects
•
Severe, protracted
malnutrition
•
Non-islet cell tumor
•
Secretes IGF-II
•
Secretes IGFI-
BP inhibitor
Case 1
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
Hypoglycemia: Family Hx of DM?
Hypoglycemia: Family Hx of DM?
Access to insulin?
Access to oral hypoglycemia agents?
Case 2
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
Case 2
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
