Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s result from

hypoglycaemia 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 ...

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 min ...

. 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 intra ...

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, using ...

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'', an ...

, and relief of symptoms when plasma glucose concentration is increased. It was first described by the

pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

surgeon In modern medicine, a surgeon is a medical professional who performs surgery. Although there are different traditions in different times and places, a modern surgeon usually is also a licensed physician or received the same medical training as ...

Allen Whipple Allen Oldfather Whipple (September 2, 1881 – April 6, 1963) was an American surgeon who is known for the pancreatic cancer operation which bears his name (the Whipple procedure) as well as Whipple's triad. Whipple was born to missionary paren ...

, 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

, 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

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

, 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 on ...

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 Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distr ...

) due to hypoglycaemia were found to be cured by

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...

to remove an

, 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 substance A reducing sugar is any sugar that is capable of acting as a reducing agent. In an alkaline solution, a reducing sugar forms some aldehyde or ketone, which allows it to act as a reducing agent, for example in Benedict's reagent. In such a reac ...

s as an indirect measure of blood

, 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 required ...

s and metabolites such as

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

, 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 end ...

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.

References

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

Definition

Differential diagnosis

History

See also

References