ERM2 - Hypoglycemia

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Author:
jknell
ID:
184689
Filename:
ERM2 - Hypoglycemia
Updated:
2012-11-20 16:25:04
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Endocrine Reproductive Pathology
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Description:
Endocrine and Reproductive Pathology
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  1. What is hypoglycemia
    • -plasma glucose concentration low enough to cause sx
    • -~ 55mg/dL
  2. Insulin Functions
    • 1. Increase glucose transport into cells
    • 2. Increase glucose utilization and ATP generation
    • 3. Increase production of glycogen in LV and SKM
    • 4. Increase AA absorption and protein synthesis
    • 5. Increase TG synthesis
  3. Glucagon Functions
    • 1. Increase breakdown of glycogen (glycogenolysis)
    • 2. Increase breakdown of fats to FAs
    • 3. Increase hepatic glucose synthesis
  4. Whipple's Triad
    • 1. hypoglycemic sx
    • 2. low plasma glucose
    • 3. reversal of sx with food or glucose
  5. Hypoglycemia: Symptoms
    • 1. Autonomic
    •      -diaphoresis
    •      -hunger
    •      -paresthesias
    •      -tremulousness
    •      -palpitations
    •      -anxiety

    • 2. Neuroglycopenic
    •      -cognitive impairement
    •      -visual changes
    •      -behavioural changes
    •      -weakness
    •      -lethargy
    •      -dizziness
    •      -seizures
    •      -coma
  6. Primary Defenses Against Hypoglycemia
    • -decreased insulin
    • -increased glucagon
    • -increased Epi (accentuates insulin and glucagon responses)
  7. Late Defenses Against Hypoglycemia
    • -increased growth hormone (increased lipolysis, antagonize insulin)
    • -increased cortisol (increase lipolysis, prot catabolism and liver gluconeogenesis)
  8. DDx of Hypoglycemia
    • 1. Insulin Mediated
    • -endogenous hyperinsulinism
    • -exogenous hyperinsulinism

    • 2. Non-Insuling Mediated
    • -drugs, alcohol
    • -critical illnesses
    • -non-islet tumor
  9. Endogenous Hyperinsulinism
    -failure to suppress insulin levels as glucose falls

    • Pro-insulin: increased
    • C peptide: increased
    • insulin: increased

    • BHB levels < 2.7 mM/L (insulin inhibits ketogenesis)
    • Increase glucose >25 mg/dL in response to glucagon
  10. Causes of Endogenous Hyperinsulinism
    • 1. Insulinoma
    • 2. Non-insulinoma Pancreatogenous Hypoglycemia Syndrome
    • 3. Autoimmune Hyperinsulinism (anti-insulin Ab)
  11. Insulinoma
    • -neuroendocrine tumor of islet cells
    • -typically have fasting hypoglycemia
    • -can be part of MEN1
    • -less than 10% become malignant
  12. NIPHS
    • -nesidioblastosis: diffuse islet hypertrophy/hyperplasia
    • -typically post prandial hypoglycemia
    • -very rare: can develop months after gastric bypass
  13. Non-Endogenous Hyperinsulinism
    1. Medication-Induced
  14. Medication-Induced Hypoglycemia
    • -Sulfoylureas: stimulate insulin secretion
    • -Meglitinides: stimulate insulin secretion

    • Pro-Insulin: increased
    • C-peptide: increased
    • Insulin: increased

    *distinguish from endogenous hyperinsulinism with SFU panel
  15. Causes of Non-Insulin Mediated Hypoglycemia
    • 1. Non-islet cell tumor hypoglycemia
    • 2. Autoimmune hypoglycemia
    • 3. Alcohol-related hypoglycemia
  16. Non-islet cell tumor hypoglycemia
    • -seen in a small number of patients with non-islet cell tumors
    • -usually large tumors

    MOA: secrete a form of IGF-II that has insulin-like activity (incompletely processed, has less affinity for IGFBP than WT --> increased free IGF-II)

    • Pro-insulin: suppressed
    • C-peptide: suppressed
    • Insulin: suppressed
  17. Autoimmune Hypoglycemia
    • 1. Abs to endogenous insulin
    • -unregulated binding/dissociation of the Ab to insulin leads to hyperinsulinism

    • 2. Abs to insulin R
    • -activation of the R in the absence of insulin
  18. Alcohol-Related Hypoglycemia
    -during fasting in normal ppl gluconeogenesis in the liver is responsible for the majority of glucose production

    -Alcohol metabolism produces excess NADH, shunting precursors away from the gluconeogenesis pathway

    --> inhibits gluconeogenesis

    -also tend to be malnourished and have poor hepatic glycogen stores
  19. Treatment of Hypoglycemia
    • -tx underlying disorder
    • -dietary modification (frequent small meals)
    • -surgery
    • -medical therapy to control sx in unresectable disease
  20. Medications used to tx hypoglycemia
    • 1. diazoxide: decreases insulin secretion
    • 2. Octreotide: inhibits insulin secretion
    • 3. Verapamil/Phenytoin: may decrease insulin secretion
    • 4. Glucocorticoids: increase insulin resistance
    • 5. Everolimus: inhibits mTOR

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