[[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[paraneoplastic Syndromes|paraneoplastic syndrome]] caused by the [[Secretions|secretion]] of [[serotonin]][[5-hydroxytryptamine|(5-hydroxytrptamine]]) but can be caused by [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]].[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of [[midgut]].70% of [[tryptophan]] is converted into [[serotonin]] which leads to secondary deficiency of [[niacin]].[[Serotonin]] metabolizes into [[5-hydroxy indoleacetic acid (5-HIAA]]) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]].Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]]. [[Carcinoid]] [[tumors]] arising in the [[bronchi]] reach the [[systemic]] [[circulation]] before passing through the [[liver]] and may be associated with [[bronchoconstriction]] and manifestations of [[carcinoid]] [[syndrome]] without [[liver]] [[Metastases|metastases.]] [[Bronchospasm]] leading to [[wheezing]] is caused by release of [[histamine]] and [[serotonin]]. [[5-HT2B receptor|5-HT2B]] is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]]. [[Fibrosis]] leads to [[Tricuspid]] and [[Pulmonic Regurgitation|pulmonic]] [[regurgitation]], [[pulmonary stenosis]] and [[Cardiac arrythmia|cardiac arrhythmias]][[arrhythmias|.]] [[Serotonin]] and [[TGF-beta]] secreted by [[Neuroendocrine tumor|neuroendocrine tumors]] and appears to play a central role in the development of [[mesenteric]] [[fibrosis]]. [[Carcinoid]] [[tumors]] are normally found throughout the [[gastrointestinal]] [[tract]] from [[mouth]] to [[anus]], with the highest concentration of [[cells]] in the [[appendix]] and [[small intestine]]. [[Lung]] is the second most common site for [[Neuroendocrine tumour|neuroendocrine tumours]] . In the [[gastric]] or [[intestinal]] [[wall]], [[Carcinoid|carcinoids]] may occur as firm [[white]], yellow, or gray [[nodules]] and may be [[intramural]] [[masses]] or may protrude into the lumen as [[polypoid]] [[nodules]]. NETs arise from [[enterochromaffin]] [[cells]] which refers to the ability to stain with [[potassium]] [[chromate]] (chromaffin), a feature of [[cells]] that contain [[serotonin]].
[[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[paraneoplastic Syndromes|paraneoplastic syndrome]] caused by the [[Secretions|secretion]] of [[serotonin]] [[5-hydroxytryptamine|(5-hydroxytrptamine]]) but can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]].[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of [[midgut]]. In patients with carcinoid syndrome, 70% of [[tryptophan]] is converted into [[serotonin]] which leads to secondary deficiency of [[niacin]]. [[Serotonin]] is metabolized into 5-hydroxy indoleacetic acid (5-HIAA) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]]. Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]]. [[Carcinoid]] [[tumors]] arising in the [[bronchi]] reach the [[systemic]] [[circulation]] before passing through the [[liver]] and may be associated with [[bronchoconstriction]] and manifestations of [[carcinoid]] [[syndrome]] without [[liver]] [[Metastases|metastases.]] [[Bronchospasm]] leading to [[wheezing]] is caused by release of [[histamine]]. [[5-HT2B receptor|5-HT2B]] is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]]. [[Fibrosis]] leads to [[Tricuspid]] and [[Pulmonic Regurgitation|pulmonic]] [[regurgitation]], [[pulmonary stenosis]] and [[Cardiac arrythmia|cardiac arrhythmias]][[arrhythmias|.]] [[Serotonin]] and [[TGF-beta]] are secreted by [[Neuroendocrine tumor|neuroendocrine tumors]] and appear to play a central role in the development of [[mesenteric]] [[fibrosis]]. [[Carcinoid]] [[tumors]] are normally found throughout the [[gastrointestinal]] [[tract]] from [[mouth]] to [[anus]], with the highest concentration of [[cells]] in the [[appendix]] and [[small intestine]]. [[Lung]] is the second most common site for [[Neuroendocrine tumour|neuroendocrine tumours]] . In the [[gastric]] or [[intestinal]] [[wall]], [[Carcinoid|carcinoids]] may occur as firm [[white]], yellow, or gray [[nodules]] and may be [[intramural]] [[masses]] or may protrude into the lumen as [[polypoid]] [[nodules]]. Neuroendocrine tumors arise from [[enterochromaffin]] [[cells]]. The name "enterochromaffin" refers to the ability to stain the cell with [[potassium]] [[chromate]] (chromaffin), a feature of [[cells]] that contain [[serotonin]].
=Pathophysiology=
=Pathophysiology=
* [[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[Paraneoplastic Syndromes|paraneoplastic syndrome]] associated with the [[Secretions|secretion]] of several [[humoral]] factors.<ref name="pmid30133565">{{cite journal |vauthors=Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP |title=Carcinoid syndrome: update on the pathophysiology and treatment |journal=Clinics (Sao Paulo) |volume=73 |issue=suppl 1 |pages=e490s |date=August 2018 |pmid=30133565 |pmc=6096975 |doi=10.6061/clinics/2018/e490s |url=}}</ref>
* [[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[Paraneoplastic Syndromes|paraneoplastic syndrome]] associated with the [[Secretions|secretion]] of several hormones.<ref name="pmid30133565">{{cite journal |vauthors=Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP |title=Carcinoid syndrome: update on the pathophysiology and treatment |journal=Clinics (Sao Paulo) |volume=73 |issue=suppl 1 |pages=e490s |date=August 2018 |pmid=30133565 |pmc=6096975 |doi=10.6061/clinics/2018/e490s |url=}}</ref>
* The primary marker is [[serotonin]] ([[5-hydroxytryptamine|5-hydroxytrptamine]]) but can be caused by [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]]
* The primary marker is [[serotonin]] ([[5-hydroxytryptamine|5-hydroxytrptamine]]) but the syndrome can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]]
*[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of [[midgut]].
*[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of the [[midgut]].
*[[Serotonin]] and [[kallikrein]] are inactivated in the [[liver]] and manifestations of [[Carcinoid Syndrome|carcinoid syndrome]] do not occur until there are [[metastases]] to the [[liver]].
*[[Serotonin]] and [[kallikrein]] are inactivated in the [[liver]] and the manifestations of [[Carcinoid Syndrome|carcinoid syndrome]] do not occur until there are [[liver]] [[metastases]].
*Exceptions include circumstances in which [[venous]] [[blood]] draining from a [[carcinoid]] [[tumor]] enters directly into the [[systemic]] [[circulation]] which are followings:
*Exceptions include circumstances in which [[venous]] [[blood]] draining from a [[carcinoid]] [[tumor]] enters directly into the [[systemic]] [[circulation]]:
#Primary [[pulmonary]] or [[ovarian]] [[carcinoid]]
#Primary [[pulmonary]] or [[ovarian]] [[carcinoid]]
#[[Pelvic]] or [[retroperitoneal]] involvement by [[metastatic]] or [[locally]] [[invasive]] [[small bowel]] [[Carcinoid Tumor|carcinoid]].
#[[Pelvic]] or [[retroperitoneal]] involvement by [[metastatic]] or [[locally]] [[invasive]] [[small bowel]] [[Carcinoid Tumor|carcinoid]].
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*Only 1% of dietary [[tryptophan]] is converted into [[serotonin]]. However, in a patient with [[neuroendocrine tumors]], up to 70% of [[tryptophan]] is converted into [[serotonin]].
*Only 1% of dietary [[tryptophan]] is converted into [[serotonin]]. However, in a patient with [[neuroendocrine tumors]], up to 70% of [[tryptophan]] is converted into [[serotonin]].
*[[Serotonin]] undergoes oxidative reaction and leads to the formation of [[5-hydroxy indoleacetic acid (5-HIAA]]) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]].
*[[Serotonin]] undergoes oxidative reaction and leads to the formation of [[5-hydroxy indoleacetic acid (5-HIAA]]) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]].
*[[Serotonin]] causes increased [[motility]] and [[secretions]] resulting in [[diarrhea]].
*[[Serotonin]] causes increased [[motility]] and [[secretions]] of the GIT resulting in [[diarrhea]].
*As most of the body's [[tryptophan]] is diverted to [[serotonin]] formation pathway by [[neuroendocrine]] [[tumors]], it leads to a [[deficiency]] of [[tryptophan]] which is needed for [[synthesis]] of [[niacin]].
*As most of the body's [[tryptophan]] is diverted to [[serotonin]] formation pathway by [[neuroendocrine]] [[tumors]], [[tryptophan]] (which is needed for niacin synthesis) becomes deficient.
*Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]].
*Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]].
*[[Prostaglandins]] also mediate increased [[intestinal]] [[motility]] and [[fluid]] [[secretion]] in [[gastrointestinal]] [[tract]] causing [[diarrhea]].
*[[Prostaglandins]] also mediate increased [[intestinal]] [[motility]] and [[fluid]] [[secretion]] in [[gastrointestinal]] [[tract]] causing [[diarrhea]].
*The [[flushing]] results from [[secretion]] of [[kallikrein]], the [[enzyme]] that [[catalyzes]] the conversion of [[kininogen]] to [[lysyl]]-[[bradykinin]].
*Skin [[flushing]] results from the [[secretion]] of [[kallikrein]], the [[enzyme]] that [[catalyzes]] the conversion of [[kininogen]] to [[lysyl]]-[[bradykinin]].
*[[Lysyl]]-[[bradykinin]] is further converted to [[bradykinin]], a strong [[vasodilators|vasodilator.]]
*[[Lysyl]]-[[bradykinin]] is further converted to [[bradykinin]], a strong [[vasodilators|vasodilator.]]
*Large amounts of [[serotonin]] produces [[pellagra]]-like features including [[diarrhea]].
*Large amounts of [[serotonin]] produces [[pellagra]]-like features including [[diarrhea]].
Carcinoid syndrome is encountered uncommonly and most often with tumors of large size (>5 cm).
Left upper lobe": A lung lobe 185x110x55mm with bronchovascular remnants up to 25mm. Arising in the hilum and involving the bronchus is a rubbery tan-pink tumor 21x20x19mm. The tumor is 6mm from the bronchovascular margins and 3mm from the hilar margin. 26mm from the tumor and 1mm from the pleura there is a firm white nodule 6mm. Peripheral to the tumor is an area where the lung shows dilated bronchi up to 12mm in diameter which lie 2mm from the pleura.Source: Radiopedia
↑Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG (September 1986). "Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue". N. Engl. J. Med. 315 (11): 663–6. doi:10.1056/NEJM198609113151102. PMID2427948.
↑Grozinsky-Glasberg S, Grossman AB, Gross DJ (2015). "Carcinoid Heart Disease: From Pathophysiology to Treatment--'Something in the Way It Moves'". Neuroendocrinology. 101 (4): 263–73. doi:10.1159/000381930. PMID25871411.
↑Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, Maroteaux L (February 1996). "Ras involvement in signal transduction by the serotonin 5-HT2B receptor". J. Biol. Chem. 271 (6): 3141–7. PMID8621713.
↑Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B (December 2002). "Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells". Am. J. Pathol. 161 (6): 2209–18. doi:10.1016/S0002-9440(10)64497-5. PMID12466135.
↑Luis SA, Pellikka PA (January 2016). "Carcinoid heart disease: Diagnosis and management". Best Pract. Res. Clin. Endocrinol. Metab. 30 (1): 149–58. doi:10.1016/j.beem.2015.09.005. PMID26971851.
↑Druce MR, Bharwani N, Akker SA, Drake WM, Rockall A, Grossman AB (March 2010). "Intra-abdominal fibrosis in a recent cohort of patients with neuroendocrine ('carcinoid') tumours of the small bowel". QJM. 103 (3): 177–85. doi:10.1093/qjmed/hcp191. PMID20123681.
↑Pantongrag-Brown L, Buetow PC, Carr NJ, Lichtenstein JE, Buck JL (February 1995). "Calcification and fibrosis in mesenteric carcinoid tumor: CT findings and pathologic correlation". AJR Am J Roentgenol. 164 (2): 387–91. doi:10.2214/ajr.164.2.7839976. PMID7839976.
↑Daskalakis K, Karakatsanis A, Stålberg P, Norlén O, Hellman P (January 2017). "Clinical signs of fibrosis in small intestinal neuroendocrine tumours". Br J Surg. 104 (1): 69–75. doi:10.1002/bjs.10333. PMID27861745.
↑General Information About Gastrointestinal (GI) Carcinoid Tumors.<ref name="pmid2886072">Duh QY, Hybarger CP, Geist R, Gamsu G, Goodman PC, Gooding GA, Clark OH (July 1987). "Carcinoids associated with multiple endocrine neoplasia syndromes". Am. J. Surg. 154 (1): 142–8. PMID2886072.
↑Karatzas G, Kouraklis G, Karayiannakis A, Patapis P, Givalos N, Kaperonis E (June 2000). "Ampullary carcinoid and jejunal stromal tumour associated with von Recklinghausen's disease presenting as gastrointestinal bleeding and jaundice". Eur J Surg Oncol. 26 (4): 428–9. doi:10.1053/ejso.1999.0911. PMID10873367.
↑Fujimori M, Ikeda S, Shimizu Y, Okajima M, Asahara T (September 2001). "Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor". Cancer Res. 61 (18): 6656–9. PMID11559529.
↑Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (August 2010). "The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems". Pancreas. 39 (6): 707–12. doi:10.1097/MPA.0b013e3181ec124e. PMID20664470.
↑Aubry MC, Thomas CF, Jett JR, Swensen SJ, Myers JL (June 2007). "Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients". Chest. 131 (6): 1635–43. doi:10.1378/chest.06-2788. PMID17400673.
↑Klöppel, Günter; Anlauf, Martin (2005). "Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract". Best Practice & Research Clinical Gastroenterology. 19 (4): 507–517. doi:10.1016/j.bpg.2005.02.010. ISSN1521-6918.
↑Nehar D, Lombard-Bohas C, Olivieri S, Claustrat B, Chayvialle JA, Penes MC, Sassolas G, Borson-Chazot F (May 2004). "Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours". Clin. Endocrinol. (Oxf). 60 (5): 644–52. doi:10.1111/j.1365-2265.2004.02030.x. PMID15104570.
↑Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV, Kidd M (September 2010). "Chromogranin A--biological function and clinical utility in neuro endocrine tumor disease". Ann. Surg. Oncol. 17 (9): 2427–43. doi:10.1245/s10434-010-1006-3. PMID20217257.