Reactive hypoglycemia may take several forms. In a diabetic patient, it may result from the administration of too much insulin or, less commonly, too much oral antidiabetic medication. In a patient with mild diabetes (or in the early stages of diabetes mellitus), reactive hypoglycemia may result from delayed and excessive insulin production after carbohydrate ingestion. Increased physical activity without a change in insulin dosages can also lead to hypoglycemia. Similarly, a nondiabetic patient may suffer reactive hypoglycemia from a sharp increase in insulin output after a meal. Sometimes called postprandial hypoglycemia, this type of reactive hypoglycemia usually disappears when the patient eats something sweet. In some patients, reactive hypoglycemia may have no known cause (idiopathic reactive) or may result from total parenteral nutrition for gastric dumping syndrome or from impaired glucose tolerance.

Fasting hypoglycemia usually results from an excess of insulin or insulin–like substance or from a decrease in counter regulatory hormones. It can be exogenous, resulting from external factors, such as alcohol or drug ingestion, or endogenous, resulting from inorganic problems. Endogenous hypoglycemia may result from tumors or liver disease. Insulinomas, small islet cell tumors in the pancreas, secrete excessive amounts of insulin, which inhibits hepatic glucose production. These tumors are usually benign (in 90% of patients). Extrapancreatic tumors, although uncommon, can also cause hypoglycemia by increasing glucose utilization and inhibiting glucose output. Such tumors occur primarily in the mesenchyma, liver, adrenal cortex, GI system, and lymphatic system. They may be benign or malignant.

Among nonendocrine causes of fasting hypoglycemia are severe hepatic diseases, including hepatitis, cancer, cirrhosis, and liver congestion associated with heart failure. All of these conditions reduce the uptake and release of glycogen from the liver.

Endocrine causes include destruction of pancreatic islet cells; adrenocortical insufficiency,
which contributes to hypoglycemia by reducing the production of cortisol and cortisone needed for gluconeogenesis; and pituitary insufficiency, which reduces corticotropin and growth hormone levels.