Blood prostaglandin activity associated with noradrenaline-provoked flush in the carcinoid syndrome

Abstract

A case of the carcinoid syndrome with unusual skin lesions is described. A rise in blood prostaglandin activity associated with noradrenaline-induced flushing is reported. The significance of prostaglandins in the carcinoid syndrome is discussed. CASE REPORTA 73-year-old widow was referred with a 2-year history of an itchy rash on the abdomen. Itching preceded the formation of blisters, each of which healed over a period of about 6 weeks to leave a white scar-like lesion. After i year the blistering ceased, but the itching persisted. Over the same period, she admitted to attacks of flushing of the face. These occurred between one and six times a day, and each lasted about a minute. She also complained of diarrhoea with up to three semi-formed motions per day. She had noted that flushing coincided with her bowel action and also exacerbated her itching. During the first year of her illness she had lost over 12 kg in weight, but recently there had been an increase in weight due to the development of congestive cardiac failure, with swelling of the legs and abdomen, and increasing breathlessness.On examination there was gross telangiectasia of the face and neck, both in the form of dilated venules and dot-like petechial angiomata (Fig. i). A difluse erythema involved both the dorsa and palms of the hands. On the abdomen there were many white macules each with a halo of erythema and telangiectasia (Figs. 2 and 3).In addition, she was in congestive cardiac failure with signs of tricuspid valve incompetence and stenosis. The liver was enlarged four fingers' breadth below the right costal margin, and its edge was nodular. InvestigationsThe diagnosis of the carcinoid syndrome was confirmed by finding the 24 h urinary excretion of 5hydroxyindoleacetic acid to be increased to between 200 and 400 mg (normal 4-14 mg). The serum alkaline phosphatase was raised to 116 units (normal 20-90 units), suggesting the presence of hepatic secondary deposits. This was confirmed by a liver scan which showed several filling defects. No F 547

Cutaneous manifestations of the malignant carcinoid syndrome

“…Foregut tumours produce histamine which has been demonstrated to be responsible for their characteristic brighter pink flush 7 . The cyanotic midgut flush is more complex, and multiple mediators are likely to be involved including serotonin, 7 tachykinins such as the vasodilating peptide bradykinin, 8 and prostaglandins 9 . The observation that chronic flushing may eventually become permanent and evolve into a rosacea‐like picture 10 raises interesting questions regarding the pathogenesis of rosacea and the role of circulating vasodilators in the development of vascular ectasia.…”

“…7 The cyanotic midgut flush is more complex, and multiple mediators are likely to be involved including serotonin, 7 tachykinins such as the vasodilating peptide bradykinin, 8 and prostaglandins. 9 The observation that chronic flushing may eventually become permanent and evolve into a rosacea-like picture 10 raises interesting questions regarding the pathogenesis of rosacea and the role of circulating vasodilators in the development of vascular ectasia. Pellagra dermatitis and dependent oedema are the result of diversion by the tumour of up to 60% of dietary tryptophan down the 5-hydroxyindole pathway in the production of serotonin (5-HT) and its urinary metabolite 5-HIAA.…”

Gastrointestinal carcinoids: Extrahepatic metastases and symptomatology following resection

“…Although serotonin has caused post-capillary vasoconstruction, resulting in a flush that becomes dusky after a few minutes, not all flushing appears to be due to this agent [9] . Injection of catecholamines has caused cutaneous flushing in patients with carcinoid syndrome.…”

Cutaneous findings related to cardiovascular disorders

“…The cardiovascular system can be involved, even in the absence of flushing, with endocardial plaque, tricuspid insufficiency, myocardial involvement with conduction defects, pulmonary stenosis, and heart failure. 142,143…”