Whipple's triad
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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 An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a mi ...
. The essential conditions are symptoms of hypoglycaemia, low
blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', '' number concentration'', ...
, and relief of symptoms when plasma glucose concentration is increased. It was first described by the
pancreatic The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocr ...
surgeon Allen Whipple, who aimed to establish criteria for exploratory pancreatic surgery to look for insulinoma.


Definition

Whipple's triad is stated in various versions. The essential conditions are: # Symptoms known or likely to be caused by hypoglycaemia, especially after
fasting Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...
or intense exercise. # A low blood plasma
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
concentration measured at the time of the symptoms. This may be measured as a blood plasma glucose concentration of less than 550
milligrams The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
per
litre The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3 ...
. # Relief of symptoms when glucose level is increased. 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 test A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic ...
s 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 Idiopathic postprandial syndrome, colloquially but incorrectly known by some as hypoglycemia, describes a collection of clinical signs and symptoms similar to medical hypoglycemia but without the demonstrably low blood glucose levels which charac ...
) in which symptoms suggestive of hypoglycaemia occur, but low glucose levels cannot be demonstrated. The criteria are now invoked far more often by
endocrinologist Endocrinology (from ''endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events ...
s 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 An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a mi ...
, and other conditions will also be considered. The same signs may be caused by
hyperinsulinism Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for o ...
not caused by insulinoma.


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 An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a mi ...
, 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 Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
, no way had yet been found to measure
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
s and metabolites such as insulin, with no imaging procedures for internal organs such as the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...
. 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. For this reason, Whipple's triad is also known as Whipple's criteria.


See also

*
Hyperinsulinism Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for o ...
*
Hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
* Causes of hypoglycemia


References

{{DEFAULTSORT:Whipple's Triad Symptoms and signs: Endocrinology, nutrition, and metabolism Medical triads