Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 27-06: The Hypoglycemic States + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Symptoms begin at plasma glucose levels of ~60 mg/dL (3.3 mmol/L), brain function impairment at ~50 mg/dL (2.8 mmol/L) Two types of spontaneous hypoglycemia: fasting and postprandial Fasting: Often subacute or chronic; usually presents with neuroglycopenia Postprandial: Relatively acute, with symptoms of neurogenic autonomic discharge (sweating, palpitations, anxiety, tremulousness) +++ General Considerations +++ Fasting hypoglycemia ++ Endocrine disorders (eg, hypopituitarism, Addison disease, myxedema) Liver malfunction (eg, acute alcoholism, liver failure) End-stage chronic kidney disease on dialysis In absence of endocrine disorders, rule out hyperinsulinism due to Either pancreatic B-cell tumors, iatrogenic, or surreptitious administration of insulin or sulfonylurea Hypoglycemia caused by extrapancreatic tumors Alcohol-related hypoglycemia Due to hepatic glycogen depletion combined with alcohol-mediated inhibition of gluconeogenesis Most common in malnourished alcohol abusers However, can occur in anyone unable to ingest food after an acute alcoholic episode followed by gastritis and vomiting +++ Postprandial (reactive) hypoglycemia ++ May be seen after gastrointestinal surgery and is particularly associated with the dumping syndrome after gastrectomy and Roux-en-Y gastric bypass surgery Occult diabetes very occasionally presents with postprandial hypoglycemia Rarely, it occurs with islet cell hyperplasia–the so-called noninsulinoma pancreatogenous hypoglycemia syndrome + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Whipple triad is characteristic of hypoglycemia regardless of the cause A history of hypoglycemic symptoms An associated low plasma glucose level (40–50 mg/dL) Relief of symptoms upon ingesting fast-acting carbohydrates in approximately 15 minutes Weight gain can result from overeating to relieve symptoms Symptoms often develop in the early morning, after missing a meal, or occasionally after exercise Because of hypoglycemic unawareness, autonomic symptoms may be mild or late and the initial symptoms are due to neuroglycopenia Blurred vision Headache Feelings of detachment Slurred speech Weakness Personality changes may occur and range from anxiety to psychotic behavior Convulsions or coma may occur if symptoms are ignored and untreated +++ Differential Diagnosis ++ Fasting hypoglycemia Hyperinsulinism: pancreatic B-cell tumor and surreptitious insulin or sulfonylureas Extrapancreatic tumors Postprandial early hypoglycemia: alimentary (eg, postgastrectomy) Postprandial late hypoglycemia: functional (increased vagal tone), occult diabetes mellitus Delayed insulin release resulting from B-cell dysfunction Counterregulatory deficiency Idiopathic Alcohol-related hypoglycemia Immunopathologic hypoglycemia: antibodies to insulin receptors, which act as agonists Pentamidine-induced hypoglycemia Islet hyperplasia (noninsulinoma pancreatogenous hypoglycemia syndrome) + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ An elevated circulating proinsulin level (> 5 pmol/L) in the presence of fasting hypoglycemia is characteristic of most B-cell adenomas and does not occur in factitious hyperinsulinism In patients with epigastric distress, history of renal calculi, or menstrual or erectile dysfunction, obtaining a serum calcium, gastrin, or prolactin level may be useful in screening for MEN-1 associated with insulinoma Obtain samples of plasma glucose, insulin, C-peptide, proinsulin, sulfonylurea screen, serum ketones, and antibodies to insulin when fingerstick blood glucose is < 50 mg/dL Patient should undergo an inpatient supervised 72-hour fast when outpatient observation does not result in symptoms or hypoglycemia and when the clinical suspicion remains high Insulinoma patients become symptomatic when plasma glucose drops to subnormal levels, because inappropriate insulin secretion restricts ketone formation Diagnostic criteria for insulinoma after a 72-hour fast are listed in Table 27–12 ++Table Graphic Jump LocationTable 27–12.Diagnostic criteria for insulinoma after a 72-hour fast.View Table||Download (.pdf) Table 27–12. Diagnostic criteria for insulinoma after a 72-hour fast. Laboratory Test Result Plasma glucose < 45 mg/dL (2.5 mmol/L) Plasma insulin (RIA) ≥ 6 microunits/mL (36 pmol/L) Plasma insulin (ICMA) ≥ 3 microunits/mL (18 pmol/L) Plasma C-peptide ≥ 200 pmol/L (0.2 nmol/L, 0.6 ng/mL) Plasma proinsulin ≥ 5 pmol/L Beta-hydroxybutyrate ≤ 2.7 mmol/L Sulfonylurea screen (including repaglinide and nateglinide) Negative ICMA, immunochemiluminometric assays; RIA, radioimmunoassay. + Treatment Download Section PDF Listen +++ +++ Medications +++ Inoperable pancreatic B-cell tumors ++ Diazoxide Divided doses of 300–400 mg/day usually suffice although an occasional patient may require up to 800 mg/day Hydrochlorothiazide, 25–50 mg daily, can be used to counteract the sodium retention and edema as well to potentiate diazoxide's hyperglycemic effect Octreotide, 50 mcg subcutaneously twice daily +++ Surgery ++ Surgical treatment for endocrine tumors +++ Therapeutic Procedures +++ Inoperable pancreatic B-cell tumors ++ Carbohydrate feeding every 2–3 h +++ Postprandial (reactive) hypoglycemia ++ Frequent feedings with smaller portions of less rapidly assimilated carbohydrate combined with more slowly absorbed fat and protein +++ Functional alimentary hypoglycemia ++ Support and mild sedation are mainstays of therapy Dietary manipulation is an adjunct: reduce proportion of carbohydrates in the diet, increase the frequency and reduce the size of the meals + Outcome Download Section PDF Listen +++ +++ Complications ++ Indiscriminate use and overinterpretation of glucose tolerance tests have led to an overdiagnosis of functional hypoglycemia As many as one-third or more of normal individuals have blood glucose levels as low as 40–50 mg/dL with or without symptoms during a 4-h glucose tolerance test + References Download Section PDF Listen +++ + +Bernard V et al. Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia. Eur J Endocrinol. 2013 Apr 15;168(5):665–74. [PubMed: 23392213] + +Cryer PE et al; Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009 Mar;94(3):709–28. [PubMed: 19088155] + +Mathur A et al. Insulinoma. Surg Clin North Am. 2009 Oct;89(5):1105–21. [PubMed: 19836487]