Hypoglycemic Disorders

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

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)

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

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

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