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Background: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality., Methods: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes., Results: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase)., Conclusions: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication., Methods: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127)., Findings: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects., Conclusions: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt., (© 2018 S. Karger AG, Basel.)

Background: Carcinoid heart disease (CHD) is an important complication of metastatic neuroendocrine disease, requiring regular monitoring to enable intervention prior to right heart failure. We aimed to identify the most appropriate echocardiographic scoring systems for the quantitative assessment of CHD., Methods: In this prospective study conducted between April and October 2012 in two European Neuroendocrine Tumor Society (ENETS) Centres of Excellence, patients with neuroendocrine tumours with liver metastases and/or carcinoid syndrome underwent transthoracic echocardiography and blood sampling for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA). Each patient was assessed according to six echocardiographic scoring systems. The individual scoring systems' feasibility, observer variability, sensitivity, specificity and correlation with the concentration biomarkers were determined., Results: 100 patients were included; 21% had echocardiographic evidence of CHD. All scores discriminated highly between those with/without CHD, with no single score performing significantly better than another. The severity, determined using all of the scoring systems, correlated with the concentration of both biomarkers, but the strongest correlations were seen between the Bhattacharyya score and serum NT-proBNP., Conclusion: All scoring systems are comparable in terms of sensitivity and specificity for the detection of CHD. There is a variation in the feasibility of the scoring systems due to varying complexity of the score components. All scores correlate with NT-proBNP and plasma 5-HIAA. The Westberg score appears to be the most optimal scoring system for use in screening of CHD whereas the more complex scoring systems are more suited to the patient with established disease who may require surgical intervention., (© 2014 S. Karger AG, Basel)

Background: It is well established that the serotonergic system (SS) plays important roles in the pathogenesis of cardiovascular diseases. However, the impact of serotonin and its inter-relation with the sympathoadrenal system (SAS) in chronic heart failure (CHF) is poorly understood., Methods: Utilizing high-performance liquid chromatography with electrochemical detection, we determined blood plasma levels of serotonin (5-hydroxy-triptamine, [5-HT](p)), 5- hydroxy-indole-acetic acid ([5-HIAA](p)), epinephrine ([E](p)), norepinephrine ([NE](p)), 3,4-dihydroxy-L-phenyl-alanine ([DOPA](p)), dopamine ([DA](p)) and the platelet concentration of serotonin ([5-HT](pt)) in CHF patients with different morphofunctional alterations of myocardium. The morphofunctional alterations included diastolic dysfunction (DD), diastolic dysfunction with left ventricular hypertrophy (DD&LVH), and diastolic and systolic dysfunction (D&SD)., Results: All CHF groups showed significant rises of [5-HT](p) and [5-HT](pt). DD&LVH and D&SD individuals also had increased [5-HIAA](p). Levels of SAS blood biomarkers were also significantly changed. The correlation between SS and SAS was increased in CHF and corresponded with disease severity., Conclusions: These results clearly demonstrate that in CHF patients significant changes in SS and SAS occur, which are thought to relate to the morphofunctional alterations of myocardium. The observed changes in the levels of these biomarkers may serve as potential surrogates to monitor severity of disease, to evaluate response to drug treatment, and as a rational basis for new therapeutic approaches., (Copyright 2009 S. Karger AG, Basel.)

Serotonin has been implicated to play an important role in regulating emotions and behavior, and it is well accepted that the platelet serotonergic system mirrors the presynaptic central serotonergic system. Since prevalence of psychiatric problems increases with age and women are known to be more vulnerable than men, the present investigation was carried out to study the relationship between serotonin activity and age in women. Levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in platelets and plasma in women (n = 49) aged 40-84 years (30 women aged 40-60 years and 19 women aged 61-84 years). There was a significant age difference between the two groups (mean: 47.6 +/- 5.91 years in the younger and 73.0 +/- 6.83 years in the older women, respectively, p < 0.00001). Platelet 5-HT as well as 5-HIAA levels were significantly higher in older women as compared to those in the younger women (89.41 +/- 21.95 ng/10(8) platelets in younger vs. 112.9 +/- 36.07 in older women, p < 0.02, and 1.20 +/- 1.10 in younger vs. 2.19 +/- 1.88 ng/10(8) platelets in older women, p < 0.05, respectively). Pearson correlation coefficients determined in the combined group (n = 49) showed a significant positive correlation between platelet 5-HT and age (r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older women compared to those in the younger women (4.50 +/- 3.20 in younger vs. 1.04 +/- 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative correlation was observed between plasma 5-HT and age (r = -0.44, p < 0.002). Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT levels in the younger group were independent of ethnicity. Since high serotonin activity has also been associated with psychiatric problems, our results of increased concentration of platelet 5-HT as well as 5-HIAA with age may have implications in predisposing aging women to behavioral/psychiatric problems.

In order to investigate a possible relationship between serotonergic and fibrinolytic systems, serotonin (5-hydroxytryptamine, 5-HT) metabolism was modified by the use of a monoamine oxidase inhibitor (tranylcypromine: 10 mg/kg body weight) and its effect on the fibrinolytic system was analyzed. Tranylcypromine caused a rise in whole blood 5-HT with a simultaneous fall in 5-hydroxyindoleacetic acid. Euglobulin clot lysis time was significantly prolonged 1 and 4 h after injection and tissue plasminogen activator (tPA) activity declined 4 h following administration with a simultaneous increase in its inhibitor (PAI) activity. Blood 5-HT was negatively related to tPA (r = -0.48; p < 0.05) and positively to PAI activities (r = 0.43; p < 0.05) in tranylcypromino-treated rats, whereas there were no such correlations in solvent-treated rats.

The platelet has been suggested to be a peripheral model of the central serotonergic neuron. This investigation was carried out in order to test the hypothesis that levels of serotonin (5-HT) in the platelet will be decreased in Alzheimer's disease (AD) since neurochemical studies suggest that levels of 5-HT are decreased in the brain of AD patients. We investigated platelet and plasma 5-HT in a group of AD patients (n = 22) as well as in age-matched normal control subjects (n = 20). The results show that the platelet level of 5-HT was significantly reduced in AD (65.7 +/- 28.41 ng/10(8) platelets in AD vs. 112.9 +/- 35.11 ng/10(8) platelets in controls; p = 0.0001). There was no effect on the levels of its metabolite 5-hydroxyindoleacetic acid. These findings suggest that the peripheral serotonergic system in AD is adversely affected.

The effects of water immersion restraint stress on collagen-induced platelet aggregation in whole blood, and on the fibrinolytic and serotonergic systems in rats have been studied. One hour long stress caused a release of tissue plasminogen activator (tPA) into the blood and a shortening of euglobulin clot lysis time (ECLT), whereas restraint of longer duration was responsible for a reduction in platelet aggregation, an elevation in the activity of plasminogen activator inhibitor with a concomitant fall in tPA and a prolongation of ECLT relative to controls. Whole-blood and plasma serotonin and its metabolite 5-hydroxyindoleacetic acid were also higher in the stressed rats and whole-blood serotonin level showed a negative correlation with tPA in the stressed rats. Either stress and/or its duration are responsible for changes in both fibrinolytic and serotonergic systems.

Renal clearance of endogenous 5-HIAA has been shown to be similar to that of PAH in humans. The present study compared 5-HIAA and PAH clearances in rats. It showed that the clearance of 5-HIAA in rats was identical to that of inulin and creatinine. This suggests that in this species, 5-HIAA is only filtered and not secreted by the tubules in contrast to what is observed in humans.

Twenty-two patients with moderate to severe carcinoid syndrome received Sandostatin in doses ranging from 50 to 500 micrograms b.i.d. subcutaneously in addition to their usual drug therapies. Symptoms were reported improved in 60% of patients following a test period of Sandostatin. Lack of effect was observed in 5 patients and a lethal complication (obstructing intestinal tumour) occurred in 1. Of 13 patients who received Sandostatin for 3-36 months, 9 remain under control; 3 patients died - 1 from carcinoid spread and the other 2 from unrelated causes. Side effects have been few and mild. In summary, Sandostatin is a valuable agent in the management of carcinoid syndrome.

The concentration of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in various body fluids was measured during the perinatal period in two groups of infants born with normal and pathological conditions, respectively. Evidence was obtained showing that fetal blood 5-HT level was relatively stable, uninfluenced by maternal or fetal factors, and was about half the value of the maternal blood. High levels of 5-HIAA and evidence of an active decomposition of 5-HT were found in the amniotic fluid. These findings suggest that 5-HT in utero is subjected to a very active metabolic turnover. The origin of the fetal blood 5-HT and the significance of the placenta in the control of intrauterine 5-HT metabolism is discussed. There was no clear evidence of abnormal 5-HT metabolism in toxemic pregnancies, premature babies, and an infant with Down's syndrome in the perinatal period.