Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: three case examples.

The results for plasma 5-hydroxyindoleacetic acid (5-HIAA), whole blood serotonin and the chromogranins on three patients following their treatment for carcinoid disease with somatostatin analogues are presented. Two of the patients (a 56-year-old woman and a 55-year-old man) demonstrated a good clinical response following treatment, with initial high blood serotonin and plasma 5-HIAA concentrations showing a significant decline. However, blood serotonin concentrations remained above the reference range during the course of treatment, whereas plasma 5-HIAA remained borderline high or marginally elevated with respect to the clinical cut-off concentration. The third patient, a 79-year-old man, demonstrated saturation of platelets with serotonin and increasing elevation of plasma 5-HIAA, which later fell with the introduction of interferon into this patient's treatment regimen. Results for the plasma chromogranin fragments, pancreastatin (Chromogranin A) and GAWK (Chromogranin B), showed a much greater degree of variability in all three cases. This study shows promise for plasma 5-HIAA as a useful marker for monitoring carcinoid disease. The limitations of blood serotonin expressed to the platelet count are highlighted.

Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family.

Hereditary coproporphyria (HCP) is the least common of the three autosomal dominant acute porphyrias. To compare the sensitivity of metabolite measurements for the identification of asymptomatic HCP, we carried out a molecular and biochemical investigation of a large family in which HCP is caused by a previously unreported frameshift mutation (c.119delA). Thirteen of 19 asymptomatic family members, aged 10-72 years, were shown by mutational analysis to have HCP. The faecal coproporphyrin isomer III:I ratio was increased in all of these 13 family members; faecal total porphyrin concentration and urinary porphyrin excretion were increased in 11 and 8 of them, respectively. Plasma porphyrin concentrations were marginally increased in three individuals and plasma fluorescence emission scanning showed a porphyrin peak at 618 nm in two of these. Our results add to the evidence that an increased faecal porphyrin coproporphyrin III:I ratio is a highly sensitive test for the detection of clinically latent HCP in individuals over the age of 10 years; its sensitivity below this age remains uncertain. They also show that plasma fluorescence emission scanning is not useful for the investigation of families with HCP.

Micronutrient concentrations in patients with malignant disease: effect of the inflammatory response.

BACKGROUND: Micronutrient deficiencies may occur in patients with malignancy due to a variety of possible causes, including unbalanced dietary intake and adverse effects of treatment. In addition, many patients show signs of a chronic inflammatory response, which can affect circulating concentrations of certain vitamins and trace elements. Our aim was to examine the effect of the inflammatory response, as determined by plasma C-reactive protein (CRP) concentrations, on a range of micronutrients in patients with malignancy. METHODS: Blood samples were collected from 50 patients with various malignancies for the measurement of vitamins A, E, C and B(1), the trace elements copper, zinc, selenium and manganese and the inflammatory marker CRP. Vitamin A was measured as retinol and vitamin E as alpha-tocopherol. Vitamin C measurement included both ascorbic acid and dehydroascorbic acid. The vitamins were assayed by high-performance liquid chromatography and the trace elements by atomic-absorption spectroscopy. RESULTS: Concentrations of zinc and selenium below their respective reference ranges and copper and manganese above their respective reference ranges were commonly found in the cancer group. However, none of these elements showed any significant correlation with CRP (P >0.01). Reduced levels of vitamin A, C and B(1) were commonly found in the cancer group. Vitamins A and C showed a significant negative correlation with CRP (r(s)=-0.66, P <0.0001 and r(s)=-0.53, P = 0.0005, respectively). Vitamin E showed no correlation with CRP. CONCLUSION: The inflammatory response is a major consideration in the interpretation of vitamin A and C concentrations in patients with malignancy.

Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease.

BACKGROUND: Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaffin cells. Current biochemical investigation usually involves the measurement of 5-hydroxyindole-3-acetic acid (5-HIAA) in 24-h urine collections. Because of the problems associated with urine collections (i.e. inconvenience, accuracy of collection and requirement for preservatives) two alternative markers, fasting plasma 5-HIAA and whole blood serotonin (5-hydroxytryptamine), have been studied. METHODS AND RESULTS: Whole blood serotonin concentration and plasma and urine 5-HIAA concentrations were measured by high-performance liquid chromatography in 31 patients suspected of having carcinoid and 26 known carcinoid patients. Receiver operator characteristic curve analysis of the data showed no statistical difference between the three markers (P>0.01) with regard to their discriminating function. However, fasting plasma 5-HIAA assay showed greater stability than whole blood serotonin assay and is more convenient for the patient than a 24-h urine collection. At a cut-off value of 118 nmol/L plasma 5-HIAA assay showed a sensitivity of 89%, a specificity of 97% and a test efficiency of 93%. Whole blood serotonin assay was further limited by its saturation in platelets at 40 nmol/10(9) platelets which made it less suitable for monitoring the treatment of carcinoid disease. CONCLUSION: Fasting plasma 5-HIAA concentration provides a more convenient screening test for carcinoid and overcomes the problems associated with 24-h urine collections, without any loss of diagnostic precision.

Measurement of phenylalanine and tyrosine in plasma by high-performance liquid chromatography using the inherent fluorescence of aromatic amino acids.

An isocratic high-performance liquid chromatography (HPLC) method is described using the natural fluorescence of phenylalanine and tyrosine compared with that of an internal standard N-methyl phenylalanine. Plasma precipitated with 6% perchloric acid was separated isocratically using a base-deactivated C18 column with 5% acetonitrile in water as the mobile phase. Fluorescent measurements at an excitation wavelength of 215 nm and emission 283 nm showed only three peaks for tyrosine, phenylalanine and the internal standard eluting within 9 min. Inter-batch coefficients of variation for phenylalanine were 2.9% and 1.8% at levels of 70 and 567 mumol/L, respectively, and 2.9% at a level of 63 mumol/L for tyrosine. The results for phenylalanine for this method showed a small mean positive bias (11 mumol/L) when compared with the target all-method means for UK National External Quality Assessment Scheme samples (n = 31). The results for tyrosine showed a small positive mean bias (10 mumol/L) when compared with an ion-exchange chromatographic method (n = 40). This method provides a quick and simple alternative to those using HPLC with pre- or post-column derivatization for monitoring patients with phenylketonuria. It is also less subject to interferences than HPLC methods using ultraviolet detection, particularly for the early eluting tyrosine peak.