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What is the cause of the carcinoid flush?

1987; BMJ; Volume: 28; Issue: 11 Linguagem: Inglês

10.1136/gut.28.11.1413

1468-3288

A. David Smith,

Pituitary Gland Disorders and Treatments

Leading articleWhat is the cause of the carcinoid flush?Between 1952 and 1954 the constellation of clinical signs and symptoms in patients with carcinoid tumours became known as the carcinoid syndrome.'In 1953, Lembeck' isolated 5-hydroxytryptamine (5-HT, serotonin) from a carcinoid tumour.Initially it was thought that the carcinoid flush was the result of 5-HT which was known to have pharmacological vascular actions.But it is not as simple as that.Clinical observation shows there are various types of flush'-namely, a diffuse erythematous flush affecting mainly the face, neck and upper anterior chest, but often spreading over the skin of the back and affecting the abdomen and palms.This flush is usually paroxysmal and short, lasting two to five minutes.Patients with this type of flush often look normal between flushes.The second type of flush has a violatious tinge to it.It affects the same areas, but lasts longer.The nose is often shining and purple during the flush, which frequently occurs on a background of permanent cyanotic flushing.These patients usually have a very high urinary 5HIAA output.The third type of flush is usually associated with bronchial carcinoid tumours.The flushes often last several hours and may even last days.The skin becomes red and often slightly purplish and body areas other than the usual flushing areas are involved.There is profuse lacrimation and the conjunctivae are suffused.The facial skin swells and the normal facial creases become exaggerated into deep folds.This type of flushing is extremely distressing.The fourth type of flush is bright red and patchy, the red flush is a particularly vivid red and the white patches seem particularly brightly white.Patchiness is most evident around the root of the neck.This type of flushing is usually associated with gastric carcinoid tumours and excess production of histamine.These different types of flushing must have a different pharmacology and are likely to be because of different substances alone, or in concert affecting different parts of the vascular bed of the skin.Robertson et al showed that 5-HT could not be the sole substance responsible for flushing.Quite simply 5-HT did not produce a true carcinoid flush when given intra- venously, nor did its concentrations usually rise in arterial plasma during a flush.Oates et al continued the search for the carcinoid flushing substance.In a series of investigations they found that the tumour contained kallikrein and that the hepatic venous blood draining carcinoid liver metastases contained a bradykinin like substance during an induced flush.They did, however, have some patients who did not release bradykinin into the circulation during flushing attacks.At that time the bradykinin was isolated and identified by various extraction techniques and bioassays.My colleagues and 1I measured arterial blood bradykinin concentrations during provoked carcinoid flush and in some patients the concentrations clearly increased, but plasma bradykinin 1413 on August 19,