Approach to the patient with spontaneous hypoglycemia

• A spontaneous hypoglycemic event should be seen as a red flag.
• Patients should be stratified according to clinical status.
• Analysis of the hypoglycemic event offers valuable diagnostic information.
• Imaging is necessary when insulinoma is suspected.
• Treatment consists of an urgent treatment and prevention of recurrence.

Hypoglycemia is common in daily clinical practice and often occurs during the treatment of diabetes mellitus. However, a small minority of hypoglycemia encountered in clinical practice is spontaneous and thus not induced by glycemic lowering agents. These spontaneous hypoglycemic events confront the clinician with a diagnostic enigma. Although the trained clinician can recognize the autonomic and neuroglycopenic symptoms of hypoglycemia even in a patient not on insulin, it remains challenging to decipher the etiology of a spontaneous hypoglycemic event. A logical and stepwise approach to the spontaneous hypoglycemic event allows for a conclusive diagnosis. This diagnostic process consists of adequately diagnosing hypoglycemia by fulfilling Whipple's triad, stratifying patients according to their clinical status and analyzing a full hypoglycemic blood panel. A complete hypoglycemic blood panel should include the analysis of glucose, insulin, C-peptide, pro-insulin, insulin antibodies and the presence of oral hypoglycemic agents. For patients with episodes of hypoglycemia induced by excessive endogenous insulin, additional imaging is often required to detect the presence of an underlying insulinoma. By diagnosing the underlying cause of the spontaneous hypoglycemia, the physician also diagnosis the mechanism by which the hypoglycemic event occurs. Allowing for a problem orientated therapeutic approach.MethodologyThe present review is based upon a comprehensive PubMed search between 1985 and 2013. This uses search terms of spontaneous hypoglycemia, insulinoma, nesidioblastosis, insulin auto-immunity, noninsulinoma pancreatogenous hypoglycemia syndrome, hormone deficiency, pro-IGF II, and pro-insulin growth factor II, and cross reference searching of pivotal articles in the subject.