Urine 5-hydroxyindoleacetic acid

At MDACC, our best results for hepatic artery emboUzation with Ivalon or Gelfoam segments/ powder were observed in patients with metastatic neuroendocrine tumors to the liver (Carrasco et al. 1986). Of the 23 evaluable patients with carcinoid syndrome, 20 (87%) responded to embolization, with a median response duration of more than 11 months. The symptomatic responses correlated with a decrease in the extent of the hepatic metastases and a decrease in the urine 5-hydroxyindoleacetic acid values to a mean of 41% of pretreatment levels. Of the 20 evaluable patients with symptoms from islet cell carcinoma metastatic to the Uver, 16 (80%) achieved objective tumor regression after embolization (Carrasco et al. 1986). Sequential and periodic embolization is required for effective palUation. As many as 21 embolizations have been administered to... 

The enzymes responsible for the metabolism of serotonin are present in all of the cells containing this amine and in the Uver. Serotonin is initially oxidatively deami-nated to form 5-hydroxyindoleacetaldehyde this compound is subsequently rapidly oxidized to the major metabolite 5-hydroxyindoleacetic acid, which is excreted in the urine. Much of the serotonin released in the brain at synapses is taken back into the initial neuron by an active reuptake mechanism to be released again. 

Fig.4.54. Analysis of 5-hydroxyindoleacetic acid in a normal sample of urine. (From ref. 113 with permission of the American Association of Clinical Chemists, Washington.)...

Focusing our attention on the serotonin branch of Figure 20.21, it is seen that the initial hydroxylation reaction requires tetrahydrobiopterin, which was introduced in Chapter 16 and is discussed further here. Serotonin per se is a neurotransmitter, and it can give rise to melatonin in the pineal gland. Melatonin is synthesized at night, and is believed to be associated with the phenomenon of circadian rhythms. Serotonin is metabolized to 5-hydroxyindoleacetic acid, which is excreted in the urine. Normal 5-hydroxyindoleacetic add excretion is about 7 mg/day, whereas in carcinoid tumor patients, this may be as high as 400 mg/day. Carcinoid is an intestinal tumor that may metastasize into the liver. 

On account of the activity of these plant extracts and the isolation from them of iV,iV-dimethyltryptamine, the physiological activity of this base in humans is of interest. When injected intramuscularly, it causes hallucinations and illusions, which are characterized by their rapid appearance and brief duration (80). Apparently, dimethyltrypt-amine is rapidly metabolized and excreted mainly as indoleacetic acid, although the urine is enriched with 5-hydroxyindoleacetic acid whether this is the result of oxidation at the 5-position or stimulation of the metabolism of serotonin in the brain is not yet known (80). 

Chizhova and Ivanova (C7) studied 20 children, aged 1-12 years, under therapy for leukemia and 10 healthy children as control. A total of 15-20 g of tryptophan was administered during 5-10 days (1.5-3 g/day) to 7 children whereas 13 were given a single dose of 2-3 g. Daily determinations of urinary metabolites by paper chromatography demonstrated a disturbance of tryptophan metabolism in 19 of the 20 leukemic children before and after tryptophan loading. Kynurenine, 3-hydroxykynurenine, and anthranilic and 3-hydroxyanthranilic acids appeared in urine, whereas 5-hydroxyindoleacetic acid was absent in the majority of the young patients. The disturbances of tryptophan metabolism were similar in all of them. Administration of vitamin Be restored tryptophan metabolism to normal in the majority of the patients. 

Degg TJ, Allen KR, Barth JH. Measurement of plasma 5-hydroxyindoleacetic acid in carcinoid disease an alternative to 24-h urine collections Ann Clin Biochem 2000 37 (Pt 5) 724-6. 

Goldenberg H. Specific photometric determination of 5-hydroxyindoleacetic acid in urine. Chn Chem 1973 19 38-44. 

Hydroxyindoleacetic acid. This acid (5-HIA) is the degradation product of serotonine (5-hydroxytryptamine). Urinary elimination of over 15 mg per day renders probable the diagnosis of a metastasising carcinoid, provided the influence of diet (bananas, walnuts etc.) is excluded. Standard amounts of 5-HIA and increasing amounts of the urine extract are applied to the adsorbent in the semi-quantitative determination of Schmid and Kuschke [143]. After the TLC-separation, the plate is sprayed, with 0.1% 2,6-dichloroqiiinonechloroiniide solution in methanol and the spot sizes compared in the approximate evaluation. Especially distinct, brownish-red spots are obtained by spraying with diazotised p-nitroaniline (Fig. 173). This reaction also can be adapted to quantitative determination [143 a]. 

Fig. 2.3. Diagnostic flow-chart in the differentiation of defects of biogenic amine neurotransmitter metabolism. The correct differential diagnosis depends on the pattern of amines and their metabolites in either urine, CSF or plasma. represents increased values, [ represents lowered values. 5HIAA 5-hydroxyindoleacetic acid HVA homovanillic acid 5HT serotonin 30MD 3-0-methyldopa DOPAC dihydroxyphenylacetic acid 3MT 3-methoxytyramine NMN norme-tanephrine VMA vanillylmandelic acid DOPS dihydroxyphenylserine MHPG 3-methoxy-4-hydroxyphenylglycol Y yes N no. Plasma and CSF levels have not been analysed but they probably reflect those seen in urine. For interpretation of quantitative results see pathological values.

This is a tumour of argentaffin cells (cells which stain with silver salts), usually sited in the ileum or appendix, or less commonly in the bronchus, pancreas or stomach. These cells normally synthesize the hormone serotonin (5-hydroxytryptamine) which is a powerful smooth-muscle stimulant and vasoconstrictor. In carcinoid syndrome this hormone is secreted in excess amounts. The clinical symptoms of this condition include flushing, diarrhoea and bronchospasm. Carcinoid syndrome can be diagnosed biochemically by detection of the serotonin metabolite, 5-hydroxyindoleacetic acid, in excess amounts in the urine. 

An intermediate in the conversion of tryptophan to 5-hydroxy tryptamine (serotonin). In some cases of carcinoid syndrome it i excreted in large amounts in the urine, even though the 5 hydroxyindoleacetic acid excretion may be normal. This i thought to be because the cells lack the decarboxylase whicl converts 5-hydroxytryptophan to 5-hydroxytryptamine. 

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