2/8 Hypoglycemia and Insulinoma - Amorosa Flashcards
why is hypoglycemia so problematic?
glucose is critical to CNS, which needs glucose and O2 to fx
- 20% of daily energy expenditure goes toward producing glucose for CNS
- brain can metabolize ketoacids as alternative, but that requires a slow adaptation
- therefore, decline in brain clucose is CRISIS
body responses to decline in glucose
neuroendocrine and adrenergic response
1. pancreas
- decr insulin
- incr glucagon
2. brain
- pituitary
- incr growth hormone
- incr ACTH → cortisol (adr cortex)
- SNS outflow
- adrenal medulla → epi
- SNS postgang neurons → norepi, Ach
gluconeogenic response
- decr insulin, incr glucagon, incr epi → stimulates liver to produce glucose (from FFA)
- decr insulin, incr epi → stimulates kidney to produce glucose
hormonal response to falling blood sugar
signs/sx of hypoglycemia
NEUROGENIC (adrenergic or sympathetic: NE and E)
- anxiety, sweating, tremor, tachycardia, HTN, palpitations, nausea
NEUROGLYCOPENIC
- blurry vision, headache, drowsiness, confusion, aggression, memory loss, coma, seizures
Whipple’s triad
definition of hypoglycemia
signs/sx that indicate hypoglycemia vs nonspecific activation of SNS
- fasting hypoglycemia ( < 45 )
- symptomatic
- value depends on brains acclimation
- sx can occur with rapid decline into or above normal range (bc brain acclimates to steady state glucose and reacts against any change in that steady state)
- immediate resolution of sx with interventions raising glucose level
ddx hypoglycemia
FUNCTIONAL
- reactive (idiopathic, mostly postprandial)
- other (factitious, iatrogenic, pseudohypoglycemic, ketogenic, alcoholic, nonhypogly)
ORGANIC (usually fasting) : structural issues
- neuroendo tumor (insulinoma)
- islet cell hyperplasia: priimary/inborn or secondary/post-bariatric-surg
- IgF1 tumors, IgF2 sarcomas
- disorders of glucose homeostasis (liver, kidney, CHF, pituitary, adrenals)
- autoimmune
ractive or post-prandial hypoglycemia
earliest sign of DM2
- delay in first phase insulin secrtion to carbohydrate load
- accentuated second phase insulin secretion → precipitous drop in glucose
seen with accelerated gastring emptying following GI surg or some kind of imbalanced GI auto tone
ketotic hypoglycemia (childhood)
ex. very active child
- activity → oxidation of all stored glycogen (muscle and liver) → insulin decline initiates lipolysis and ketogenesis
- brain is slow to change fuel source form glucose to beta-hydroxybutyrate oxidation
- child becomes lethargic or hysterical or ill w hypoglycemia
alcoholic hypoglycemia
- alcohol metabolism blocks gluconeogenesis by depleting energy producing substrates (NAD)
- depleted hypatic glycogen reserves (bc fasting/not eating)
- alc metabolism requires alcohol dehydrogenase → incr cell redox state (NADH+/NAD)
- lack of NAD → gluconeogenesis is decr
- over time, brain metabolism adjusts to tolerate hypoglycemia
- incr SNS activity and glucagon and suppressed insulin response is supposed to overcome hypoglycemia →→→ alcoholic keoacidosis
pseudohypoglycemia
potential causes
- glucose falls about 7/hr for every 10,000 WBC
- RBC will consume glucose if test tube is untreated
- drawing from hematomas in fingertips (from coagulopathy)
insulinoma
fasting/post-absorptive hypoglycemia
- beta cell hyperplasia (nesidioblastosis)
- neonatal presentation
- post gastric bypass surgery
- large tumor mass or ectopic production of IgF1 by stromal tumors, IgF2 by mesenchymal tumors
- autoimmune disorders: abs to insulin or insulin receptor
clinical hypoglycemia
tests
- glucose
- insulin, insulin/glucose
- C-peptide
- proinsulin
- beta hydroxybutyrate
- sulfonylurea and meglitinide screen
- anti-insulin ab
dx when…
number for inapprop insulin level for glucose value?
high insulin with low proinsulin, c-peptide, sulfonylurea, anti-insulin ab?
v high anti-insulin abs, all other markers low?
if I/G > 0.3, abnormal (normal = 0.1)
high insulin with low proinsulin, c-peptide, sulfonylurea, anti-insulin ab?
insulin use
v high anti-insulin abs, all other markers low?
SLE, rheumatoid arthritis, etc
hypoglycemic unawareness
repeated hypoglycemia attenuates counterreg sympathetic response → no sx of hypoglycemia
