Hypoglycemia redux

Thank you to Katie Sullivan for presenting a case last Thursday of a patient with hypoglycemia and eosinophilia who was found to have pan hypo pit.
In these pearls: https://ucsfmed.wordpress.com/2016/08/10/zsfg-endocrine-report-hypoglycemia/ We talked about organizing the hypoglycemia ddx by organ system and a good first pass workup. This time, we organized it differently – insulin-mediated vs insulin-independent. See below.
Insulin mediated
  • Exogenous
    • insulin
    • sulfonylureas (either due to excess intake or decreased clearance)
  • Endogenous
    • islet cell hyperplasia
    • insulinoma
    • Adrenal insufficiency
non-Insulin mediated
  • glucose consumption doesn’t meet demand
    • poor access to food
    • giant, rapidly divided tumors that consume all glucose
  • malabsorption of glucose (for example after gastric surgery)
  • decreased glycogen stores or poor gluconeogenesis
    • malnutrition
    • liver failure
    • ESRD
    • adrenal insufficiency
  • decreased glucagon
    • Lisa Murphy pearl! In any pancreatic failure state (chronic pancreatitis, post pancreatectomy), the patient loses both their alpha and beta cells. So not only do they develop diabetes, they have hard to manage hypoglycemia because they don’t make glucagon.
Bonus Lisa Murphy Pearls
  • Growth hormone is an under appreciated player in the hypoglycemia orchestra. It’s one of the counter-regulatory hormones, along with cortisol and glucagon. Growth hormone stimulates hepatic gluconeogenesis and reduces glucose utilization in the peripheral tissues.
    • While attempting to figure out the mechanism here, I found this only mildly relevant NEJM article from 1962 that provides some early experimental evidence about what growth hormone does.  It uses unfortunate terminology like “panhypopituitary dwarfs”. A good reminder that medical literature has come a long way in describing patients respectfully.
  • Hormone loss in pan hypo pit
    • When the pituitary is compressed or lost slowly over time, the hormone production disappears in a very evolutionarily rational way. The reproduction and growth-related hormones go first, while the necessary for life hormone (cortisol) goes last.
      • In other words, hormones are usually lost in this order:  Growth hormone -> gonadotropins-> thyroid hormones -> cortisol
  • Hypoglycemia in ESRD – pro tips
    • two mechanisms
      • gluconeogenesis – 20% in the kidneys, 80% in the liver
      • uremia impairs hepatic glycogen uptake
    • We talk often about ESRD as a risk factor for hypoglycemia. Lisa explained that ESRD-induced hypoglycemia is rare in isolation.  Along with ESRD, a patient needs a second hit to the counter-regulatory cascade – food insecurity, liver failure, adrenal insufficiency – to have clinically detectible hypoglycemia from ESRD.

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