I found a referenced answer in a tweet by Dr Tony Breu from January 2023. I have linked to acknowledge my source, but I have no affiliation or interest.
I have provided his references below and added my own to expand on it.
Serotonin
Serotonin (5-hydroxytryptamine) is a monoamine neurotransmitter with many functions. It and other substances (e.g. histamine) are produced in excess by neuroendocrine tumours.
Receptors for serotonin are expressed in a multiple sites.
Serotonin is derived from tryptophan and it is broken down by enzymes in the monoamine oxidase family to 5-hydrocyindoleacetic acid (5-HIAA); high levels of this can be detected in the urine of people with carcinoid syndrome. The metabolism is shown below.
Image from American Journal of Physiology. 2008. The love of a lifetime: 5-HT in the cardiovascular system.
Serotonin and heart valves
A serotonin (5-HT2B) receptor is expressed in all heart valves and its activation leads to the histopathological features found in carcinoid syndrome; activation of interstitial cells resulting in fibrosis.
This is similar to how some drugs can cause heart valve problems, by stimulating these same receptors, without the action of serotonin itself.
Right v left
The explanation for why carcinoid affects the right heart valves more frequently than the left (the opposite of what is found in drug-induced valve fibrosis), is that monoamine oxidase in the lungs inactivates serotonin.
Serotonin from the systemic circulation reaches the right side of the heart but is inactivated in the lungs before returning to the left side of the heart.
This also explains why carcinoid in the lungs is more likely to affect the left-sided heart valves - the secreted serotonin is less likely to be inactivated before reaching the left side of the heart. A right-to-left shunt in the heart (such as a patent foramen ovale) can bypass the lungs and lead to left-sided valve disease.
Physiology
This diagram summarises the metabolism of serotonin (5-HT) in carcinoid.
Interestingly, the liver normally removes a lot of serotonin from the portal circulation in first-pass metabolism, but serotonin arising from other sources like the foregut, lung or ovary can exert an effect before it is metabolised.
Image from Reviews in Endocrine and Metabolic Disorders. 2017. Echocardiography in functional midgut neuroendocrine tumors: When and how often.
In the diagram, normal physiological movement of serotonin is shown in blue, with pathological movement shown in red, showing the potential burden on the right side of the heart.
References
Robiolio et al. Circulation. 1995. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography.
Bhattacharyya et al. Lancet. 2009. Drug-induced fibrotic valvular heart disease.
Baseman et al. Neurology. 2004. Pergolide use in Parkinson disease is associated with cardiac valve regurgitation
Alabaster and Bakhle. British Joirnal of Pharmacology. 1970. Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs
Yuan. Brazilian Journal of Cardiovascular Surgery. 2016. Valvular Disorders in Carcinoid Heart Disease.
