Whipple's triad

Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma glucose concentration, and relief of symptoms when plasma glucose concentration is increased. It was first described by the pancreatic surgeon Allen Whipple, who aimed to establish criteria for exploratory pancreatic surgery to look for insulinoma.

Not to be confused with Whipple's disease or Whipple procedure.
Whipple's triad
Other namesWhipple's criteria
Symptomssymptoms of hypoglycaemia, low blood plasma glucose concentration, relief of symptoms when plasma glucose concentration increased
Differential diagnosishypoglycemia

Definition

Whipple's triad is stated in various versions. The essential conditions are:

  1. Symptoms known or likely to be caused by hypoglycaemia, especially after fasting or intense exercise.[1][2] These symptoms include tremor, tachycardia, anxiety, dizziness, and loss of consciousness.[3]
  2. A low blood plasma glucose concentration measured at the time of the symptoms.[1][2] This may be measured as a blood plasma glucose concentration of less than 550 milligrams per litre.[2]
  3. Relief of symptoms when glucose level is increased.[1][2]

The use and significance of the criteria have evolved over the last century as understanding of the many forms of hypoglycaemia has increased and diagnostic tests and imaging procedures have improved. Whipple's criteria are no longer used to justify surgical exploration for an insulinoma, but to separate "true hypoglycaemia" (in which a low glucose can be demonstrated) from a variety of other conditions (e.g., idiopathic postprandial syndrome) in which symptoms suggestive of hypoglycaemia occur, but low glucose levels cannot be demonstrated. The criteria are now invoked far more often by endocrinologists than by surgeons. The radiological investigation of choice now is endoscopic and/or intraoperative ultrasonography.

Differential diagnosis

Whipple's triad is not exclusive for insulinoma, and other conditions will also be considered.[2] The same signs may be caused by hyperinsulinism not caused by insulinoma.[4]

History

The criteria date back to the 1930s, when a few patients with hypoglycaemic symptoms (such as shakiness, syncope, or sweating) due to hypoglycaemia were found to be cured by surgery to remove an insulinoma, but a large proportion of people with symptoms suggestive of hypoglycaemia apparently had no need of surgery. Diagnostic testing was rudimentary; beyond a crude assay for reducing substances as an indirect measure of blood glucose, no way had yet been found to measure hormones and metabolites such as insulin, with no imaging procedures for internal organs such as the pancreas.

Allen Whipple was a well-known surgeon who had pioneered pancreatic surgery. He proposed that no pancreatic surgery to look for insulinoma be performed unless these criteria were met.[5] For this reason, Whipple's triad is also known as Whipple's criteria.

See also

References
  1. Melmed, Shlomo (2016). Williams textbook of endocrinology (13 ed.). Elsevier. pp. 1582–1607. ISBN 978-0-323-29738-7.
  2. Martens, Pieter; Tits, Jos (2014-06-01). "Approach to the patient with spontaneous hypoglycemia". European Journal of Internal Medicine. 25 (5): 415–421. doi:10.1016/j.ejim.2014.02.011. ISSN 0953-6205. PMID 24641805 – via ScienceDirect.
  3. Desimone, Marisa E.; Weinstock, Ruth S. (2000), Feingold, Kenneth R.; Anawalt, Bradley; Blackman, Marc R.; Boyce, Alison (eds.), "Hypoglycemia", Endotext, South Dartmouth (MA): MDText.com, Inc., PMID 25905360, retrieved 2023-10-27
  4. Cazabat, L.; Chanson, P. (2009-09-01). "Hypoglycémie et insulinome". Annales d'Endocrinologie. 70: S2–S11. doi:10.1016/S0003-4266(09)72470-9. ISSN 0003-4266. PMID 19878764 – via ScienceDirect.
  5. Whipple, Allen O (1938). "The surgical therapy of hyperinsulinism". International Journal of Surgery. 3: 237–276 – via Scopus.
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