Hypoglycemia--an enigmatic dilemma.

Hypoglycemia is a common disorder with a diverse etiology. True hypoglycemia, however, is probably less common than generally perceived, particularly as symptoms are commonly mimicked by a host of other disorders, both endocrine and nonendocrine. There are often individual variations in symptomatology of hypoglycemia, and some individuals can tolerate it better than others. Women are reportedly better adapted to withstand hypoglycemia and have a higher threshold than men. (1) Nonetheless, it is an important and critical diagnosis to make and should not be missed. All patients with a plasma glucose of less than 50 mg/dL warrant further investigation.

Symptoms of hypoglycemia include those of sympathetic activation resulting in diaphoresis, weakness, hunger, palpitations, and anxiety. As the glucose level continues to fall, symptoms of neuroglycopenia predominate in the form of headache, cognitive deficit, behavioral changes, seizure, and eventually coma. Sometimes these symptoms are erroneously confused with malingering and are misinterpreted as a manifestation of a psychiatric disorder. Patients may develop hypoglycemia unawareness due to recurrent hypoglycemia. (2)

One should not rely exclusively on the glucose level from a finger stick to diagnose hypoglycemia as it can be influenced by personal technique and local circulation or skin conditions. It is acceptable to perform a finger stick glucose determination in a patient suspected of hypoglycemia, but it should be confirmed by a venous sample as soon as possible. It should also be kept in mind that capillary and venous blood glucose levels may differ in the same individual. Whenever a physician is confronted with the possibility of hypoglycemia, the following conditions must be satisfied for diagnosis, which are collectively known as the Whipple triad (3) symptoms compatible with hypoglycemia, low serum glucose concentration at the time of hypoglycemic symptoms, and the alleviation of symptoms by administration of glucose.

Distinguishing fasting from postprandial hypoglycemia is the next step, which may not always be easy to accomplish. Fasting hypoglycemia is the hallmark of insulinoma, although variations can and do occur as exemplified in Prelipcean et al. (4) Patients with insulinoma generally tend to gain weight due to high caloric intake to correct their symptoms and due to the trophic effect of insulin. Weight loss in these patients by any means helps to improve insulin sensitivity and, thereby, facilitates symptomatic hypoglycemia leading to early diagnosis of insulinoma.

For best diagnostic yield, patients should undergo testing during an episode of spontaneous hypoglycemia. Alternatively, the fasting serum glucose and insulin levels may be checked, but the yield is often poor. A ratio of insulin to glucose of greater than 0.3 during fasting or a hypoglycemic state in a nondiabetic patient should alert the physician to the possibility of insulinoma. Sometimes it becomes necessary to institute a prolonged, 72-hour fast (3) to provoke hypoglycemia, and this should be done only in a supervised setting, such as a hospital. Caution should be exercised in the case of children and the elderly who have a lower threshold for seizures. Most of the patients with insulinoma (65%) become hypoglycemic within the first 24 hours. (5) Should the patients become symptomatic, or to prevent them from becoming hypoglycemic at the end of the fast, 1 mg of glucagon should be administered IV. A good response to glucagon is reflective of adequate glycogen stores in a patient with insulinoma. Localization of the tumor is the next logical step.

References

1. Merimee TJ, Fineberg SE. Homeostasis during fasting. II. Hormonesub-strate differences between men and women. JClin Endocrinol Metab 1973;37:698.

2. Mitrakou A, Fanelli C, Veneman T, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med 1993;329:834.

3. Whipple AO. The surgical therapy of hyperinsulinism. J Int Chir 1938;3:237.

4. Prelipcean MS, O'Neil PJ, Bell DSH. Hyperinsulinemic hypoglycemia precipitated by weight loss. South Med J 2005;98:726-728.

5. Service FJ, Natt N. The prolonged fast. J Clin Endocrinol Metab 2000;85:3973.

Ranjodh Gill, MD, FACP 

From the Department of Internal Medicine, Virginia Commonwealth University Health System, Richmond, VA.

Reprint requests to Ranjodh Gill, MD, Department of Internal Medicine, VCUHS, PO Box 980102, Richmond, VA 23298. Email: [e-mail]

Accepted March 23, 2005