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Objective: Carcinoid cancer patients often have elevated levels of serotonin or its precursor 5-hydroxytryptophan. Normally, serotonin synthesis accounts for a small fraction of tryptophan catabolism, which should be directed along a pathway that allows partial conversion to niacin; hence, increased diversion of tryptophan toward serotonin could cause variable degrees of niacin deficiency in carcinoid patients. Therefore, the prevalence of niacin deficiency among carcinoid patients was investigated by clinical assessment of pellagra and biochemical assessment of whole blood niacin number, a ratio derived from two biologically active forms of niacin (NAD/NADP x 100)., Methods: Clinical and biochemical niacin status were assessed in a cohort of newly diagnosed carcinoid patients with carcinoid syndrome (CCS, n = 36), carcinoid patients without carcinoid syndrome (CWCS, n = 32) and noncarcinoid controls (n = 24) recruited at two primary care clinics. Other aspects of serotonin metabolism were measured by analyses of plasma serotonin and tryptophan and urinary excretion of 5-hydroxyindoleacetic acid., Results: Biochemical niacin deficiency (niacin number < 130) was significantly more common in CCS patients (10 out of 36) compared to controls (p < 0.05, Fisher's exact test), while CWCS patients displayed an incidence that was not significantly elevated (4 out of 32). Only one CCS patient, who was also identified biochemically as niacin deficient, was clinically diagnosed with pellagra., Conclusion: Biochemical niacin deficiency is more prevalent among newly diagnosed CCS patients than in controls. Manifestation of pellagra is a less sensitive indicator, and dependence on this endpoint could lead to a lack of appropriate nutritional support for this group of patients.

We monitored long-term (median 11 months) concentrations of platelet serotonin and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine metabolites in 44 patients with carcinoid tumors. Tumor serotonin and catecholamine contents (11 patients) and urinary histamine and N-methylhistamine (15 patients) were determined. Consistently increased concentrations of indoles, notably platelet serotonin, were observed in 96%, 43%, and 0% of patients with mid-, fore-, and hindgut carcinoids, respectively. Urinary dopamine metabolites, notably 3-methoxytyramine, were consistently increased in 38%, 20%, and 7% of patients with mid-, hind-, and foregut carcinoids, respectively. For urinary norepinephrine/epinephrine metabolites, notably normetanephrine and metanephrine, these data were 33%, 20%, and 14%, respectively. Midgut carcinoid tumors had the highest serotonin contents, whereas concentrations of catecholamines were independent of primary localization. There was no consistent relation between biogenic amine contents in tumors and urinary excretion of the amine metabolites. Occurrence of carcinoid syndrome was related to increased serotonin production rate. Increased histamine production is not an important feature in patients with lung carcinoids or liver-metastasized ileum carcinoids.

We evaluated the effect of intravenous (i.v.) glucose on the plasma tryptophan (TRP) and tyrosine (TYR) concentration of 12 normal subjects, six patients with carcinoid tumors and the carcinoid syndrome (carcinoid syndrome), and five patients with carcinoid tumors without the carcinoid syndrome (tumor.) Following i.v. glucose administration, the plasma Trp concentration of the normal subjects and the tumor patients incresed, while the plasma Trp concentration of the carcinoid syndrome patients decreased. Following i.v. glucose administration, the plasma Tyr concentration of the normal subjects and the tumor patients decreased, while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The response to i.v. insulin differed in some respects from the response to i.v. glucose: the plasma Trp of normal subjects did not change while the plasma Trp of carcinoid syndrome patients decreased; the plasma Tyr of the normal subjects increased while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The carcinoid syndrome patients had high serum serotonin concentrations and impaired glucose tolerance and insulin secretion as compared to both normal subjects and tumor patients. We conclude that under appropriate experimental conditions, glucose administration can increase the plasma Trp concentration of normal human subjects.

We treated nine patients who had carcinoid tumors of the small intestine, six of whom had the carcinoid syndrome, with daily intramuscular doses of leukocyte interferon--3 X 10(6) U per day for one month and 6 X 10(6) U per day for another two months. Seven patients had previously been treated with streptozocin and fluorouracil, without benefit. Treatment with interferon ameliorated the manifestations of the carcinoid syndrome and led to prompt and continuing decreases in urinary levels of 5-hydroxyindoleacetic acid and serum levels of human chorionic gonadotropin subunits and pancreatic polypeptide in all six patients with liver metastases, but it had no clear effect in two of three patients with only lymph-node involvement. After the treatment period, five of the six responders had relapses in clinical manifestations and increases in hormone levels. We conclude that interferon is of benefit in treating metastatic small intestinal carcinoid tumors in patients with the carcinoid syndrome.