Whipple Triad: Definition, History and Current Use

It is a collection of three criteria that suggest that a patient’s symptoms are the result of a hypoglycemia that may indicate insulinoma.

A diagnosis of hypoglycaemia is not based solely on symptoms. On the contrary, endocrinologists look for the presence of Whipple’s triad. These three factors help doctors diagnose hypoglycaemia or low blood sugar levels (blood glucose).

The triad of Whipple is the clinical presentation of pancreatic insulinomas , it is established in several versions, but the essential conditions are:

  • Symptoms known or that may be caused by hypoglycemia, especially after fasting or intense exercise, fasting hypoglycemia (<50mg / dl) low blood glucose level.
  • A low plasma glucose (in plasma), measured by a precise method at the time of symptoms, is also called hypoglycaemia symptoms at the time of low glucose level.
  • Immediate relief of symptoms after administration of IV glucose, when glucose rises to normal.

The symptoms of hypoglycemia are:

  • Neuroglucopenic symptoms such as behavioral changes, fatigue, seizures, altered consciousness.
  • Adrenergic symptoms such as palpitations, tremors, anxiety.
  • Cholinergic symptoms such as sweating, hunger and altered sensations.

The cutoff value for hypoglycemia is 70 mg / dL which is equal to 3.9 mmol / L.

The relief of symptoms can be done as follows:

  • Initially 20 mg of carbohydrates containing fluids or foods can be administered if the patient can tolerate them orally.
  • Intravenous glucose 25g of bolus at 2mg / kg / min followed by 10g / h. 250 ml of 10% dextrose is better than 50 ml of 50% dextrose as there is less thrombophlebitis.
  • Glucagon 1mg subcutaneously or intramuscularly works as fast as dextrose and is a good method when there is no intravenous access available and the patient is unconscious, but it will not work in a drunk patient.

Insulinomas are clinically characterized by Whipple’s triad: episodic hypoglycaemia, central nervous system (CNS) dysfunction temporarily related to hypoglycemia (confusion, anxiety, stupor, paralysis, convulsions, coma) and dramatic reversal of central nervous system abnormalities by glucose administration.

When the Whipple triad is mentioned, one thinks classically of insulinomas, but these characteristics are not insulinoma specific.

According to the textbook Henry’s Clinical Diagnosis and Management by Laboratory Methods, a blood glucose level equal to or lower than 50 mg / dL (normal blood glucose is 80-120) without the presence of diabetes justifies an adequate medical evaluation.

Fasting or reactive hypoglycemia is diagnosed by a blood test to measure blood glucose. The test can be done after fasting during the night, physical activity or between meals.

Of course, if your endocrinologist suspects a hormonal deficiency, a pancreatic tumor or another cause of hypoglycaemia, more testing and evaluation is required.


As a good piece of trivia, one might suspect that Whipple’s disease, Whipple’s triad, and Whipple’s procedure, since they are all grouped around the same region, would all have been named by Whipple himself.

In fact, there are two Whipples. One for the disease and another for the triad and the procedure. He was appointed by Allen Oldfather Whipple (1881-1963), American surgeon.

The criteria date back to the 1930s, when it was discovered that some patients with symptoms of hypoglycaemia (such as tremors, syncope, or sweating) due to hypoglycemia could be cured by surgery to remove an insulinoma.

However, it also became evident that a large proportion of people with symptoms suggestive of hypoglycaemia did not need surgery.

Diagnostic tests were rudimentary: beyond a crude trial to reduce substances as an indirect measure of blood glucose, there was no way to measure hormones and metabolites such as insulin, or imaging procedures for internal organs such as pancreas.

Allen O. Whipple was a well-known surgeon who had been a pioneer in pancreatic surgery. In an article entitled “Surgical therapy of hyperinsulinism,” in J Internat Chir 3: 237-276 (1938), he proposed that pancreatic surgery should not be performed to look for an insulinoma unless these criteria are met.

Current use of the whipple triad

The use and importance of the criteria have evolved over the last century as our understanding of the various forms of hypoglycemia increases and our diagnostic tests and imaging procedures have improved.

The Whipple criteria are no longer used to justify the surgical exploration of an insulinoma, but to separate “true hypoglycemia” (in which a low glucose can be demonstrated) from a variety of other conditions (eg, postprandial syndrome). idiopathic) in which symptoms suggest hypoglycemia, occurs but low glucose levels can not be demonstrated.

The criteria are now invoked much more frequently by endocrinologists than by surgeons.