Carcinoid heart disease. Medical search. Frequent questions (1)

Treatment focuses on control of the underlying carcinoid syndrome, targeting subsequent valvular heart disease and managing consequent heart failure. (karger.com)

We report the gratifying response of functioning metastatic neuroendocrine tumor with carcinoid heart disease (uncontrolled by long-acting octreotide) to treatment with 177 Lu-DOTATATE. (snmjournals.org)
A 30-y-old man who had been diagnosed with a grade II jejunal neuroendocrine tumor metastatic to the liver and abdomen was found clinically and on 2-dimensional (2D) echocardiography to have the complication of carcinoid heart disease. (snmjournals.org)
However, given the patient's history of metastatic neuroendocrine tumor, as well as an elevated pro-BNP with echocardiographic evidence of severe tricuspid regurgitation, carcinoid heart disease is the most likely cause. (acc.org)
Metastatic carcinoid tumor to the heart: echocardiographic-pathologic study of 11 patients. (acc.org)
Characterization, Prognosis, and Treatment of Patients With Metastatic Lung Carcinoid Tumors. (nih.gov)
The syndrome results from vasoactive substances (including serotonin , bradykinin, histamine, prostaglandins, polypeptide hormones) secreted by the tumor, which is typically a metastatic intestinal carcinoid. (msdmanuals.com)

If a patient is thought to have carcinoid syndrome, blood and urine tests must be performed to determine levels of bioactive substances secreted by carcinoid tumors. (medscape.com)

Carcinoid syndrome is a rare condition that can occur in people with carcinoid tumors, which are slow-growing tumors that can develop in various parts of the body, such as the gastrointestinal tract, lungs, and ovaries. (icloudhospital.com)
Carcinoid syndrome is a rare condition that can occur in people with carcinoid tumors, which are slow-growing neuroendocrine tumors that usually develop in the digestive system (such as the small intestine, colon, or rectum) or in the lungs. (icloudhospital.com)
Carcinoid syndrome is a rare condition, and not all people with carcinoid tumors will develop the syndrome. (icloudhospital.com)
Carcinoid syndrome is a rare condition that can occur in people with carcinoid tumors, which are slow-growing neuroendocrine tumors that usually develop in the digestive system or in the lungs. (icloudhospital.com)
Carcinoid Syndrome Carcinoid syndrome develops in some people with carcinoid tumors and is characterized by cutaneous flushing, abdominal cramps, and diarrhea. (merckmanuals.com)

Increased amounts of serotonin can also cause the flushing seen as the main symptom of carcinoid syndrome. (wikipedia.org)
This is a common symptom of carcinoid syndrome, and it may be chronic or intermittent. (icloudhospital.com)

Advances in the management of patients with carcinoid syndrome. (harvard.edu)
The optimal management of patients with carcinoid tumors involves a multidisciplinary team of health care providers including an oncologist, gastroenterologist, surgeon, radiologist and nuclear medicine specialist. (medifocus.com)

The somatostatin analogs (SSAs) octreotide and lanreotide are used to control carcinoid symptoms and tumor progression in advanced inoperable disease. (medscape.com)
This response favorably altered the clinical course of the patient, enabling corrective valvular surgery, enhancing health-related quality of life, improving symptoms (from New York Heart Association grade III at baseline to grade I after 6 cycles), stabilizing the disease, and substantially reducing the level of 5-hydroxyindole acetic acid. (snmjournals.org)
Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors (formerly known as carcinoid tumors). (wikipedia.org)
The syndrome is caused by neuroendocrine tumors most often found in the gut releasing biologically active substances into the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction. (wikipedia.org)
The biologically active substances that are released by the tumors cause the symptoms of the carcinoid syndrome. (wikipedia.org)
These substances act on the vessels to produce the symptoms of the carcinoid syndrome. (wikipedia.org)
The symptoms of the carcinoid syndrome result from the action of these substances largely on the blood vessels. (wikipedia.org)
In the pulmonary neuroendocrine tumors or metastases, histamine release and kallikrein metabolism are the vasoactive mediators of flushing and the other symptoms of carcinoid syndrome. (wikipedia.org)
Symptoms of carcinoid crisis include flushing, hypotension, arrhythmia and bronchospasm. (wikipedia.org)
Assessment of change in quality of life, carcinoid syndrome symptoms and healthcare resource utilization in patients with carcinoid syndrome. (harvard.edu)
Impact of carcinoid syndrome symptoms and long-term use of somatostatin analogs on quality of life in patients with carcinoid syndrome: A survey study. (harvard.edu)
Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR. (harvard.edu)
A condition where some NETs produce increased levels of the hormone serotonin and cause a number of symptoms such as flushing (redness) of the face, diarrhoea (loose bowel motions), asthma or wheezing, heart failure, stomach cramps, swelling of the ankles, fast heart rate. (christie.nhs.uk)
However, carcinoid tumor cells are distinguished from most other types of tumors in that they secrete various hormone-like substances (e.g., serotonin, noradrenalin, histamines) which may cause symptoms throughout the body rather than symptoms localized to the organ where the tumor originates. (medifocus.com)
Carcinoid tumors are slow-growing tumors and most do not cause symptoms until they interfere with daily function or metastasize. (medifocus.com)
Symptoms are often associated with the site of tumor origin and reflect the tumor obstructing organs involved in normal body function but may be less specific if related to carcinoid syndrome. (medifocus.com)
Carcinoid syndrome describes a combination of symptoms that result from hormones or hormone-like substances, (e.g., serotonin, gastrin, ACTH) that are produced by some carcinoid tumors. (medifocus.com)
Carcinoid crisis - when all of the above symptoms occur at the same time. (medifocus.com)
Carcinoid tumors grow slowly, and symptoms may not occur for several years, if at all. (medscape.com)
however, even if a carcinoid tumor produces these molecules, some patients do not experience any symptoms. (medscape.com)
Symptoms of carcinoid syndrome can include flushing of the face and neck, diarrhea, wheezing or difficulty breathing, and heart palpitations. (icloudhospital.com)
If you experience symptoms of carcinoid syndrome or have concerns about a possible carcinoid tumor, it is important to seek medical attention. (icloudhospital.com)
However, carcinoid tumors can bypass the liver and release these hormones directly into the bloodstream, causing symptoms of carcinoid syndrome. (icloudhospital.com)
In people with carcinoid syndrome, these hormones are released into the bloodstream and can cause a range of symptoms, such as flushing of the face and neck, diarrhea, wheezing or difficulty breathing, and heart palpitations. (icloudhospital.com)
Symptoms of carcinoid syndrome can vary depending on the location of the tumor and the type and amount of hormones it produces. (icloudhospital.com)
Although there are different ways for an extremely rare disease to develop, it's common that they have no treatment, and people have to manage the symptoms as best they can. (bewellbuzz.com)
Treating underlying cancer can reduce symptoms, but it can develop into carcinoid heart disease, which thickens heart valves and creates leaks that can be fatal. (bewellbuzz.com)
What are Heart Transplant Rejection : Causes, Symptoms And Prevention? (lookformedical.com)
Because symptoms frequently occur relatively late during the course of valvular incompetence, the prevalence of valve lesions was assessed for patients who were exposed to these drugs but who had no obvious history of cardiac disease or cardiac symptoms. (cdc.gov)
Endocrinologically active tumors of the diffuse peripheral endocrine or paracrine system (neuroendocrine tumors) produce various amines and polypeptides with corresponding symptoms and signs, including carcinoid syndrome. (msdmanuals.com)
Metabolic products released by primary pulmonary and ovarian carcinoids bypass the portal route and may similarly induce symptoms. (msdmanuals.com)
Rare intestinal carcinoids with only intra-abdominal spread can drain directly into the systemic circulation or the lymphatics and cause symptoms. (msdmanuals.com)

The opinion of a cardiothoracic surgeon was sought, who deemed the disease inoperable because of suboptimal cardiac function. (snmjournals.org)
Heart Disease: About 60-70% of the those affected by carcinoid syndrome develop cardiac complications. (wikipedia.org)
Cardiac manifestations constitute CARCINOID HEART DISEASE. (harvard.edu)
The Central Minnesota Heart Center at St. Cloud Hospital also known as MN Heart is a comprehensive cardiac care center dedicated to the discovery, management and control of cardiac disease in the adult population. (mnheart.com)
During chest examination, a pulmonary systolic and diastolic heart murmur may be heard if cardiac involvement is present. (medscape.com)
Thickening of the endocardium of the cardiac chambers and papillary muscles and thickening and deformation of the valve cusps and chordae tendineae can lead to heart failure, influencing valvular function and causing regurgitation, stenosis, or combined functional lesions. (medscape.com)
They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. (bvsalud.org)
Alterations in the normal hepatic venous Doppler waveform often indicate cardiac dysfunction, although it may also reflect disease of the hepatic parenchyma and/or vasculature. (radiopaedia.org)
While SLE, systemic sclerosis (scleroderma), and mixed connective tissue disease may cause myocarditis, these more commonly involve the pericardium, coronary arteries, or cardiac valves. (mhmedical.com)

Left heart valves are usually spared because vasoactive substances such as serotonin are enzymatically inactivated in the lung vasculature. (karger.com)
Bochemical diagnosis of carcinoid tumors is based on the measurement of the serotonin metabolite 5-HIAA in urine. (medscape.com)
Increased amounts of serotonin lead to increased gut motility causing the diarrhea seen in carcinoid syndrome. (wikipedia.org)
If high levels of the hormone serotonin are produced over a long time, this can cause thickening of the heart valves and can lead to failure of the heart. (christie.nhs.uk)
The name was chosen to separate these tumors from ordinary malignancies (carcinomas), but by the 1950s, the fact that carcinoids could be malignant was obvious, thanks to Erspamer and Asero (1952), who identified serotonin production by carcinoid tumors. (medscape.com)
Right heart problems may develop because the tricuspid valve is stenosed by serotonin action, causing shortness of breath after a few years. (medscape.com)
Carcinoid syndrome occurs when these tumors secrete certain hormones, such as serotonin or histamine, into the bloodstream. (icloudhospital.com)
Carcinoid syndrome is triggered by the release of certain hormones, such as serotonin and histamine, from carcinoid tumors. (icloudhospital.com)
The histopathologic features were similar to those observed in carcinoid-induced valvular disease, a serotonin-related syndrome. (cdc.gov)
tryptophan is diverted to form 5-hydroxytryptophan and serotonin) and in Hartnup disease (absorption of tryptophan by the intestine and kidneys is defective). (merckmanuals.com)
An intestinal carcinoid does not usually cause carcinoid syndrome unless hepatic metastases have occurred because metabolic products released by the tumor are rapidly destroyed by blood and liver enzymes in the portal circulation (eg, serotonin by hepatic monoamine oxidase). (msdmanuals.com)
Serotonin , the primary hormone produced by carcinoid tumors, acts on smooth muscle to cause diarrhea, colic, and malabsorption. (msdmanuals.com)

Approximately 3,000 new cases of lung carcinoid tumors are diagnosed in the United States each year. (medifocus.com)

Over the years it became clear that carcinoid tumors can be quite aggressive, can metastasize, and can cause carcinoid syndrome . (medifocus.com)
It is important to note that not all tumors that produce hormones cause carcinoid syndrome. (icloudhospital.com)

Carcinoid heart disease is the result of valvular damage related to the vasoactive substances released by the neuroendocrine tumor reaching the right side of the heart. (wikipedia.org)
Ergotamine has been associated with numerous vascular complications but only rarely with fibrosing disorders or valvular heart disease. (nih.gov)
The surgically excised mitral and aortic valves were involved by a proliferative process that was strikingly similar to lesions described in patients with carcinoid heart disease and methysergide-associated valvular disease. (nih.gov)
On July 8, 1997, 24 cases of valvular heart disease in women who had been treated with fenfluramine and phentermine were publicly reported (1). (cdc.gov)
Although valvular lesions were observed on both sides of the heart, a left-sided valve was affected in all cases. (cdc.gov)
Right-sided valvular heart disease may develop after. (merckmanuals.com)

Carcinoid tumors arise from neuroendocrine cells, which are widespread in the human body, especially in the organs derived from the primitive intestine (see the image below). (medscape.com)
Overview of Carcinoid Tumors Carcinoid tumors develop from neuroendocrine cells in the gastrointestinal tract (90%), pancreas, pulmonary bronchi, and rarely the genitourinary tract. (msdmanuals.com)

Surgical options are limited to heart transplantation. (medscape.com)
Surgical management of left-sided carcinoid heart disease. (acc.org)
Does the Centers for Disease Control's NNIS system risk index stratify patients undergoing cardiothoracic operations by their risk of surgical-site infection? (doximity.com)

A section (on the right) of an intestinal carcinoid mass arising from the mucosa (150 X). Image courtesy of Professor Pantaleo Bufo, University of Foggia, Italy. (medscape.com)

Typically, 90% of carcinoid tumors originate from the distal ileum or appendix (the embryologic midgut. (medscape.com)
Hindgut Carcinoid Tumors - These tumors originate in the large intestines, specifically in the transverse colon, descending colon, and rectum. (medifocus.com)

Carcinoid heart disease: successful tricuspid valve replacement. (bmj.com)
Heterotopic Transcatheter Tricuspid Valve Replacement in a Patient With Carcinoid Heart Disease. (herzklappenzentrum.org)

The age at diagnosis varies somewhat among specific tumor locations but typically, most people diagnosed with a carcinoid tumor are in their 50s. (medifocus.com)
Diagnosis of carcinoid syndrome usually involves blood and urine tests to measure levels of certain hormones, as well as imaging tests (such as CT scans or MRIs) to locate the tumor. (icloudhospital.com)

She was subsequently admitted for acute decompensated heart failure. (acc.org)
In some cases, carcinoid tumors present as acute appendicitis or chronic pain in the lower right abdominal quadrant. (medscape.com)
Emergency TAVI for acute heart failure due to severe aortic stenosis in critically ill patients with or without cardiogenic shock [published online ahead of print, 2022 Oct 10]. (herzklappenzentrum.org)
Eur Heart J Acute Cardiovasc Care. (herzklappenzentrum.org)

Carcinoids do not produce the malignant carcinoid syndrome until they are no longer confined to the small bowel or mesentery, perhaps because the liver breaks down the secretory products of tumors restricted to those locations. (medscape.com)
This is why carcinoid syndrome most often occurs in patients whom the neuroendocrine tumor has metastasized to the liver, which allows the substances to bypass the first pass metabolism. (wikipedia.org)
Neuroendocrine tumors arising in the bronchi may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being metabolized. (wikipedia.org)
This mainly affects the right side of the heart unless there is anomalous circulation (i.e. patent foramen ovale) because the lungs will metabolize the substances released by the tumor similar to how the liver will. (wikipedia.org)
The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. (harvard.edu)
2006-2012 he was the clinical lead for "NHS Evidence" for Gastroenterology and Liver diseases (under the auspices of NICE), chairing annual evidence updates into gastrointestinal and liver disorders. (cor2ed.com)
Alterations in the normal hepatic vein waveform may reveal or confirm abnormalities in the heart or liver. (radiopaedia.org)

The course will cover the following topics: Mitral and tricuspid valves, arrhythmia, endocarditis, hypertrophic obstructive cardiomyopathy, carcinoid and aortic root. (eacts.org)
Mitral and aortic valve disease associated with ergotamine therapy for migraine. (nih.gov)
Clinical Outcome Following Transcatheter Aortic Valve Implantation in Patients With Chronic Obstructive Pulmonary Disease. (herzklappenzentrum.org)

Carcinoid tumors and related syndromes may be a part of multiple endocrine neoplasia . (medscape.com)
The heart may be involved in a number of systemic syndromes. (mhmedical.com)

Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. (medscape.com)
The carcinoid syndrome occurs in approximately 10% of all neuroendocrine tumors or about 30-40% of more advanced/well developed neuroendocrine tumors. (wikipedia.org)
The carcinoid syndrome occurs secondary to neuroendocrine tumors. (wikipedia.org)
Carcinoid heart disease occurs primarily on the right side of the heart but may involve the left side to a minimal degree. (medscape.com)
Gigantism is an extremely rare disease that occurs when there's too much growth hormone before the bone plates have fused. (bewellbuzz.com)

and asthma attacks-caused by vasoactive hormones secreted by metastases from carcinoid tumors. (medscape.com)

Carcinoid tumors share some properties with other cancer cells such as uncontrolled, overproduction of the cells that results in tumor formation and malignant potential. (medifocus.com)
A carcinoid tumor that shows atypical characteristics and has borderline malignant potential. (nih.gov)

At the time of his referral for consideration of PRRT, he presented with severe flushing, diarrhea, and dyspnea of grade III on the New York Heart Association scale, uncontrolled by monthly long-acting octreotide injection. (snmjournals.org)

These fruits are healthy because they contain potent antioxidants that can help reduce your risk of cancer and other diseases, maintain a healthy brain as you age, and lower your risk for cardiovascular disease and high blood pressure . (ourlifecare.com)

Considering the significantly shortened overall survival of patients with carcinoid heart disease, the relative paucity of available treatment options, and the risk of complications during corrective surgery on poorly controlled functioning disease, 177 Lu-DOTATATE can emerge as a potent option in this group of patients. (snmjournals.org)
Carcinoid heart disease manifests in many patients with carcinoid syndrome ( 2 ), but the prevalence dropped to approximately 20% after the introduction of newer therapies such as somatostatin analogs and 177 Lu-DOTATATE, along with everolimus, sunitinib, and the combination of capecitabine and temozolomide ( 3 ). (snmjournals.org)
Retrospective review of serotonergic medication tolerability in patients with neuroendocrine tumors with biochemically proven carcinoid syndrome. (harvard.edu)
The prognosis (outlook or chance of recovery) for patients with carcinoid tumors is based primarily on size of the tumor and the degree to which it has spread and invaded other tissues in the body. (medifocus.com)
Carcinoid heart diseases affect in more than half percent of the patients with the carcinoid tumors, got from the midgut neuroendocrine tissue. (mnheart.com)
A study found that levels of chromogranin-A (CgA) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with the presence and severity of tricuspid regurgitation as a manifestation of carcinoid heart disease among patients with neuroendocrine tumors. (acc.org)
2 Characteristic echocardiographic features of advanced carcinoid heart disease include thickening and retraction of immobile tricuspid valve leaflets with associated tricuspid regurgitation, which is severe in 90 percent of patients. (acc.org)
The Big Apple Noids support group invites you to join fellow carcinoid and neuroendocrine tumor (NET) patients and three medical experts for lunch on Sunday, May 4 from 12:30 to 3:30 pm in a private dining room at Dorrian's restaurant in Manhattan (1616 2nd Avenue, corner of 84th Street). (carcinoid.org)
Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. (bvsalud.org)

1] The heart is grossly normal, although histologic abnormalities are often present, depending on the etiology of the restrictive cardiomyopathy. (medscape.com)
However, these may be considered separate diseases because the etiology is known. (medscape.com)

Bronchoconstriction: A relatively rare symptom affects about 15% of those having carcinoid syndrome and often accompanies flushing, sneezing, and shortness of breath. (wikipedia.org)
A symptom complex associated with CARCINOID TUMOR and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. (harvard.edu)
[ 20 ] Flushing is the most frequent symptom and may be brief (eg, 2-5 min) or may last for several hours, usually in later disease stages. (medscape.com)
Malignant carcinoid syndrome is not a cause of sustained hypertension , and a rise in blood pressure during flushing is rare. (medscape.com)
Rarely, a carcinoid tumor leaks chemicals into the bloodstream and causes skin flushing, lesions, shortness of breath, and bowel changes. (bewellbuzz.com)

J Am Heart Assoc. 2023 Sep 8:e030280. (emas-online.org)

The next most common site for the development of carcinoid tumors is in the lungs. (medifocus.com)
Over time, the condition can cause damage to the heart and lungs. (icloudhospital.com)

These include Fabry disease (X-linked recessive), Gaucher disease (autosomal recessive), glycogen storage diseases, and autosomal recessive hemochromatosis. (medscape.com)

About 66% of all carcinoid tumors develop in the gastrointestinal tract. (medifocus.com)

Most carcinoid tumors are now known to be slow growing malignant tumors that have their own specific biological and clinical characteristics. (medifocus.com)
According to the American Society of Clinical Oncology (ASCO), approximately 11,500 people in the United States are diagnosed each year with a carcinoid tumor. (medifocus.com)
Many clinical studies suggest that an increase in EAT volume is associated with coronary artery disease. (go.jp)
and Dr. Jerome S. Zacks , cardiologist, Assistant Clinical Professor of Medicine at The Mt. Sinai Medical Center and founder of the Carcinoid Heart Center in New York City. (carcinoid.org)

Follow-up assays of other bioactive substances vary according to the location of the carcinoid tumor. (medscape.com)
There are over 40 substances known to be secreted by these tumors but the exact effect of each and their contribution to the carcinoid syndrome is unknown. (wikipedia.org)

Eur Heart J. 2022;ehac735. (herzklappenzentrum.org)

Carcinoid tumors are in general quite rare and occur in approximately 2.5-5 per 100,000 people. (medifocus.com)

The likelihood of developing carcinoid syndrome depends on the location and size of the tumor, as well as the type and amount of hormones it produces. (icloudhospital.com)

The echocardiogram above shows severe tricuspid regurgitation due to leaflet malcoaptation, typical for carcinoid heart disease. (acc.org)
Bronchospasms are a less common sign of malignant carcinoid syndrome but may be severe. (medscape.com)

Morphologic findings include atrial enlargement without increased ventricular wall thickness or ventricular cavity dilation, the absence of eosinophilic infiltration, and the absence of pericardial disease. (medscape.com)
3 The morphology of the valve leaflet is not disrupted and the carcinoid plaque generally affects the ventricular aspect of the tricuspid valve leaflets and the arterial aspect of the pulmonic valve cusps. (acc.org)
Takotsubo cardiomyopathy (TC) is a recently increasing diagnosed disease showed by transient apical or mid-apical left ventricular dysfunction. (docksci.com)

Predictors of Human Milk Feeding and Direct Breastfeeding for Infants with Single Ventricle Congenital Heart Disease: Machine Learning Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Registry. (cdc.gov)

Pericardial involvement is particularly common in many of the connective tissue diseases. (mhmedical.com)

However, hereditary diseases may have regional characteristics, and few data are available regarding the prevalence of FH throughout particular regions in Japan. (go.jp)

hepatic veno -occlusive disease (e.g. (radiopaedia.org)
1. Scheinfeld M, Bilali A, Koenigsberg M. Understanding the Spectral Doppler Waveform of the Hepatic Veins in Health and Disease. (radiopaedia.org)

Tryptophan metabolism is altered in the carcinoid syndrome. (wikipedia.org)
Tryptophan is also needed for niacin synthesis which can be a cause for pellagra associated with carcinoid syndrome. (wikipedia.org)

Anatomy4

Diseases6

Chemicals and Drugs1

Analytical, Diagnostic and Therapeutic Techniques and Equipment2

Underlying carcinoid syndrome1

Metastatic6

Secreted by carcinoid tumors1

People with carcinoid tumors5

Symptom of carcinoid syndrome2

Management of patients with carcinoid2

Symptoms32

Cardiac9

Serotonin12

Lung carcinoid tumors1

Cause carcinoid syndrome2

Valvular6

Neuroendocrine cells2

Surgical3

Intestinal carcinoid1

Tumors originate2

Tricuspid valve replacement2

Diagnosis2

Acute4

Liver7

Aortic3

Syndromes2

Occurs5

Metastases1

Malignant potential2

Diarrhea1

Cardiovascular1

Patients9

Etiology2

Flushing5

20231

Lungs2

Glycogen storage1

Gastrointestinal tract1

Clinical4

Substances2

20221

Occur1

Size of the tumor1

Severe2

Ventricular3

Congenital Heart D1

Connective Tissue D1

Prevalence1

Hepatic2

Tryptophan2