RARE DISEASE
Carcinoid syndrome
Carcinoid syndrome
Carcinoid syndrome
Synonyms: Malignant carcinoid syndrome
Synonyms: Malignant carcinoid syndrome
Synonyms: Malignant carcinoid syndrome
Drug discovery
9
drugs
With orphan designations
Overview
Carcinoid syndrome (CS) is a paraneoplastic condition caused by neuroendocrine tumors (NETs) secreting vasoactive substances like serotonin, leading to flushing, diarrhea, and bronchospasm. It typically arises in metastatic NETs, particularly those of small bowel or lung origin, where hepatic/lung metastases bypass hormone inactivation. Complications include carcinoid heart disease (right-sided valvular fibrosis) and life-threatening carcinoid crisis triggered by anesthesia or stress. Diagnosis relies on elevated urinary 5-HIAA and imaging [1][6][9].
Population
Burden
Cardiac: 17–50% develop carcinoid heart disease, reducing 3-year survival to 31% vs. 68% without [4][9].
Mortality: Median survival improves from 1.5 to 4.4 years with cardiac surgery and SSA use [9][15].
Quality of life: Chronic diarrhea (80% of cases) and unpredictable flushing profoundly impact daily function [16][20].
Therapies
First-line: Somatostatin analogs (octreotide/lanreotide) reduce symptoms in 65–72% of patients [3][8].
Advanced disease: Liver-directed therapies (embolization, PRRT) or surgery for cytoreduction [3][8][13].
Adjuncts: Telotristat ethyl for refractory diarrhea; perioperative octreotide to prevent crisis [3][8][15].
Categories: rare endocrine diseases, rare neoplastic diseases
Research Papers
1,759 drug discovery papers about Carcinoid syndrome, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,759 drug discovery papers about Carcinoid syndrome, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-09 | Cutaneous Manifestations of Carcinoid Tumor and Syndrome.
Carcinoid syndrome refers to the signs and symptoms a patient experiences secondary to a carcinoid tumor or another well-differentiated neuroendocrine tumor, which secretes serotonin and other peptides that enter the bloodstream; only 10% of patients with carcinoid tumors experience carcinoid syndrome. Common findings include facial flushing, tachycardia, and shortness of breath. Carcinoid tumors usually originate in the gastrointestinal (G.I.) tract. They are slow growing but can metastasize to the liver, lymph nodes, and elsewhere. Primary or metastatic cutaneous carcinoid tumors present as pink, fast-growing dermal or subcutaneous nodules. The diagnostic workup includes a thorough history and physical examination of the entire body, including a urinary 24-hour 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A. Management of carcinoid syndrome initially includes the use of somatostatin analogs, diet, medication regulation, and clinical monitoring. More aggressive treatment, such as peptide receptor radionuclide therapy or everolimus, an mTOR inhibitor, may be required.
2026-08-07 | Clinical Responses to Tarlatamab Among Patients with Pulmonary Carcinoid.
Pulmonary carcinoid (PC) is a rare, well-differentiated neuroendocrine tumor of the lung. In patients with metastatic disease, systemic therapies typically have low response rates, and long-term survival is poor. PC frequently expresses DLL3, but whether it responds to the DLL3-targeted bispecific T-cell engager tarlatamab is unknown. We analyzed 11 patients with DLL3-high PC treated with tarlatamab at Memorial Sloan Kettering. Tumor response was assessed using RECIST v 1.1. Response rate was 8/11 (73%), including one patient with central nervous system-only disease, and disease control rate was 11/11 (100%). All patients experienced reduction of their measurable disease. One patient had progressed at time of data cutoff and median progression-free survival was not reached. Cytokine release syndrome (CRS) occurred in cycle 1 in 9/11 (82%) patients including 2 with grade 3 CRS. Tarlatamab demonstrated a high response rate in PC. Cytokine release syndrome was common. Tarlatamab is a promising treatment option for patients with PC.
2026-08-03 | Effective treatment of carcinoid syndrome with peptide receptor radionuclide therapy
CLINICAL VIGNETTEThe severity of symptoms intensified over the following months; therefore, we decided to increase the frequency and escalate doses of lanreotide (120mg once every 2 weeks).However, adequate symptom control was not achieved, as complaints persisted despite partial improvement.Although imaging studies [computed tomography (CT) scans] still described the disease as stable, we observed clinical and biochemical progression, with a substantial rise in chromogranin A levels (Fig. 2).Next available treatment options were discussed, and peptide receptor radionuclide therapy 69-year-old male patient diagnosed with a midgut neuroendocrine tumor (NET) was admitted to the hospital due to aggravating symptoms of carcinoid syndrome (CS).The patient has a history of emergency laparotomy with segmental resection of the small intestine (end-to-end anastomosis) due to gangrenous perforated inflammation of Meckel's diverticulum in September 2015.Histopathological examination revealed a NET G1 of Meckel's diverticulum, with immunohistochemistry showing: synaptophysin positive, chromogranin positive, and Ki67 positive in < 2% of cell nuclei.Due to high somatostatin receptor expression demonstrated on [99mTc] HYNIC-TOC scans (Krenning score 3-4) and the presence of peritoneal implants, as well as metastases in lymph nodes, bones, and liver, the patient began therapy with long-acting somatostatin analogs in 2016 -initially octreotide 30 mg every 4 weeks; later, we switched to lanreotide 120 mg every 4 weeks.The treatment was well tolerated, and a radiological response [stable disease (SD)] was achieved according to RECIST 1.1 criteria.At the end of 2022, the patient began experiencing periodic symptoms of CS -initially sporadically, then progressively intensifying over the following months.He reported intermittent abdominal pain, diarrhea (up to 12 bowel movements per day), and facial flushing with telangiectasias (Fig. 1).We performed 24-hour urine collections for 5-hydroxyindoleacetic acid (5-HIAA), the results of which were significantly elevated.As the next step, we measured NT-proBNP to evaluate for carcinoid heart disease; the level was slightly increased -205.6 pg/mL (cut off 125) -so we did not extend the diagnostics with echocardiography, in accordance with Polish Network of Neuroendocrine Tumors and European Neuroendocrine Tumor Society recommendations [1,2].
2026-07-01 | Hepatic arterial embolization procedures in neuroendocrine tumors with carcinoid heart disease: a retrospective single-center study on safety and feasibility
Abstract Hepatic arterial embolization reduces liver tumor burden and hormonal secretion in neuroendocrine tumors, but its safety in patients with carcinoid heart disease is underexplored, and current guidelines suggest managing the cardiac disease first. We assessed the safety and efficacy of hepatic arterial embolization in patients with neuroendocrine tumors and concomitant carcinoid heart disease in a single-center retrospective study including patients with liver metastases and carcinoid heart disease confirmed on expert transthoracic echocardiography between 2001 and 2025. The primary endpoint was procedural safety; secondary endpoints were symptom control, biochemical response, and overall survival. Twenty-seven patients (median age: 58.6 years) underwent 69 embolization procedures using bland, conventional, and drug-eluting bead techniques. Severe carcinoid heart disease was present in 52% of patients, and right-sided valvular disease was found in 96%, with tricuspid regurgitation predominating. No procedure-related or cardiovascular death occurred. Two cardiac complications (7%) arose, both in patients with severe pre-existing valvular disease, together with four extra-cardiac complications. Carcinoid syndrome symptoms and urinary 5-hydroxyindoleacetic acid levels decreased significantly after treatment, whereas cardiac symptoms remained stable. The median overall survival was 6.25 years, with a 5-year survival of 60%. Hepatic arterial embolization appears feasible with an acceptable safety profile in patients with neuroendocrine tumors and concomitant carcinoid heart disease when performed in expert centers with multidisciplinary management and may contribute to carcinoid syndrome control. Prospective multicenter studies are warranted to confirm these findings and define the optimal sequencing of hepatic arterial embolization and cardiac valve surgery. Key findings
2026-06-27 | Transcatheter Tricuspid Valve Replacement in Carcinoid Heart Disease With Transjugular 3D Intracardiac Echocardiography Guidance.
Transcatheter tricuspid valve replacement (TTVR) with the EVOQUE system was the first Food and Drug Administration-approved TTVR therapy for clinical use in patients with symptomatic severe tricuspid regurgitation. Successful implantation is largely dependent on both fluoroscopic and transesophageal echocardiography (TEE) guidance. Imaging by TEE may be inadequate for confident and successful TTVR, which has led to adjunctive imaging with intracardiac echocardiography (ICE). We present a unique case of TTVR with the EVOQUE system using transjugular 3-dimensional (3D) ICE guidance in symptomatic severe tricuspid regurgitation due to carcinoid syndrome in the setting of cardiogenic shock. Transjugular 3D ICE is an effective adjunctive imaging modality for TTVR in patients who have inadequate imaging on TEE. A transjugular approach for 3D ICE offers an alternative route compared with transfemoral for real-time visualization of the tricuspid valve leaflets with no interference with the valve delivery system.
2026-08-09 | Cutaneous Manifestations of Carcinoid Tumor and Syndrome.
Carcinoid syndrome refers to the signs and symptoms a patient experiences secondary to a carcinoid tumor or another well-differentiated neuroendocrine tumor, which secretes serotonin and other peptides that enter the bloodstream; only 10% of patients with carcinoid tumors experience carcinoid syndrome. Common findings include facial flushing, tachycardia, and shortness of breath. Carcinoid tumors usually originate in the gastrointestinal (G.I.) tract. They are slow growing but can metastasize to the liver, lymph nodes, and elsewhere. Primary or metastatic cutaneous carcinoid tumors present as pink, fast-growing dermal or subcutaneous nodules. The diagnostic workup includes a thorough history and physical examination of the entire body, including a urinary 24-hour 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A. Management of carcinoid syndrome initially includes the use of somatostatin analogs, diet, medication regulation, and clinical monitoring. More aggressive treatment, such as peptide receptor radionuclide therapy or everolimus, an mTOR inhibitor, may be required.
2026-08-07 | Clinical Responses to Tarlatamab Among Patients with Pulmonary Carcinoid.
Pulmonary carcinoid (PC) is a rare, well-differentiated neuroendocrine tumor of the lung. In patients with metastatic disease, systemic therapies typically have low response rates, and long-term survival is poor. PC frequently expresses DLL3, but whether it responds to the DLL3-targeted bispecific T-cell engager tarlatamab is unknown. We analyzed 11 patients with DLL3-high PC treated with tarlatamab at Memorial Sloan Kettering. Tumor response was assessed using RECIST v 1.1. Response rate was 8/11 (73%), including one patient with central nervous system-only disease, and disease control rate was 11/11 (100%). All patients experienced reduction of their measurable disease. One patient had progressed at time of data cutoff and median progression-free survival was not reached. Cytokine release syndrome (CRS) occurred in cycle 1 in 9/11 (82%) patients including 2 with grade 3 CRS. Tarlatamab demonstrated a high response rate in PC. Cytokine release syndrome was common. Tarlatamab is a promising treatment option for patients with PC.
2026-08-03 | Effective treatment of carcinoid syndrome with peptide receptor radionuclide therapy
CLINICAL VIGNETTEThe severity of symptoms intensified over the following months; therefore, we decided to increase the frequency and escalate doses of lanreotide (120mg once every 2 weeks).However, adequate symptom control was not achieved, as complaints persisted despite partial improvement.Although imaging studies [computed tomography (CT) scans] still described the disease as stable, we observed clinical and biochemical progression, with a substantial rise in chromogranin A levels (Fig. 2).Next available treatment options were discussed, and peptide receptor radionuclide therapy 69-year-old male patient diagnosed with a midgut neuroendocrine tumor (NET) was admitted to the hospital due to aggravating symptoms of carcinoid syndrome (CS).The patient has a history of emergency laparotomy with segmental resection of the small intestine (end-to-end anastomosis) due to gangrenous perforated inflammation of Meckel's diverticulum in September 2015.Histopathological examination revealed a NET G1 of Meckel's diverticulum, with immunohistochemistry showing: synaptophysin positive, chromogranin positive, and Ki67 positive in < 2% of cell nuclei.Due to high somatostatin receptor expression demonstrated on [99mTc] HYNIC-TOC scans (Krenning score 3-4) and the presence of peritoneal implants, as well as metastases in lymph nodes, bones, and liver, the patient began therapy with long-acting somatostatin analogs in 2016 -initially octreotide 30 mg every 4 weeks; later, we switched to lanreotide 120 mg every 4 weeks.The treatment was well tolerated, and a radiological response [stable disease (SD)] was achieved according to RECIST 1.1 criteria.At the end of 2022, the patient began experiencing periodic symptoms of CS -initially sporadically, then progressively intensifying over the following months.He reported intermittent abdominal pain, diarrhea (up to 12 bowel movements per day), and facial flushing with telangiectasias (Fig. 1).We performed 24-hour urine collections for 5-hydroxyindoleacetic acid (5-HIAA), the results of which were significantly elevated.As the next step, we measured NT-proBNP to evaluate for carcinoid heart disease; the level was slightly increased -205.6 pg/mL (cut off 125) -so we did not extend the diagnostics with echocardiography, in accordance with Polish Network of Neuroendocrine Tumors and European Neuroendocrine Tumor Society recommendations [1,2].
2026-07-01 | Hepatic arterial embolization procedures in neuroendocrine tumors with carcinoid heart disease: a retrospective single-center study on safety and feasibility
Abstract Hepatic arterial embolization reduces liver tumor burden and hormonal secretion in neuroendocrine tumors, but its safety in patients with carcinoid heart disease is underexplored, and current guidelines suggest managing the cardiac disease first. We assessed the safety and efficacy of hepatic arterial embolization in patients with neuroendocrine tumors and concomitant carcinoid heart disease in a single-center retrospective study including patients with liver metastases and carcinoid heart disease confirmed on expert transthoracic echocardiography between 2001 and 2025. The primary endpoint was procedural safety; secondary endpoints were symptom control, biochemical response, and overall survival. Twenty-seven patients (median age: 58.6 years) underwent 69 embolization procedures using bland, conventional, and drug-eluting bead techniques. Severe carcinoid heart disease was present in 52% of patients, and right-sided valvular disease was found in 96%, with tricuspid regurgitation predominating. No procedure-related or cardiovascular death occurred. Two cardiac complications (7%) arose, both in patients with severe pre-existing valvular disease, together with four extra-cardiac complications. Carcinoid syndrome symptoms and urinary 5-hydroxyindoleacetic acid levels decreased significantly after treatment, whereas cardiac symptoms remained stable. The median overall survival was 6.25 years, with a 5-year survival of 60%. Hepatic arterial embolization appears feasible with an acceptable safety profile in patients with neuroendocrine tumors and concomitant carcinoid heart disease when performed in expert centers with multidisciplinary management and may contribute to carcinoid syndrome control. Prospective multicenter studies are warranted to confirm these findings and define the optimal sequencing of hepatic arterial embolization and cardiac valve surgery. Key findings
2026-06-27 | Transcatheter Tricuspid Valve Replacement in Carcinoid Heart Disease With Transjugular 3D Intracardiac Echocardiography Guidance.
Transcatheter tricuspid valve replacement (TTVR) with the EVOQUE system was the first Food and Drug Administration-approved TTVR therapy for clinical use in patients with symptomatic severe tricuspid regurgitation. Successful implantation is largely dependent on both fluoroscopic and transesophageal echocardiography (TEE) guidance. Imaging by TEE may be inadequate for confident and successful TTVR, which has led to adjunctive imaging with intracardiac echocardiography (ICE). We present a unique case of TTVR with the EVOQUE system using transjugular 3-dimensional (3D) ICE guidance in symptomatic severe tricuspid regurgitation due to carcinoid syndrome in the setting of cardiogenic shock. Transjugular 3D ICE is an effective adjunctive imaging modality for TTVR in patients who have inadequate imaging on TEE. A transjugular approach for 3D ICE offers an alternative route compared with transfemoral for real-time visualization of the tricuspid valve leaflets with no interference with the valve delivery system.
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Drug Discovery Landscape
9 orphan drug designations for Carcinoid syndrome, including 4 approved therapies.
9 orphan drug designations for Carcinoid syndrome, including 4 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Paltusotine | small molecules | EMA | 2026-08-20 | — | Crinetics Pharmaceuticals Europe GmbH |
paltusotine | small molecules | FDA | 2025-05-15 | — | Crinetics Pharmaceuticals, Inc. |
Octreotide acetate [Mycapssa] | peptides | EMA | 2023-01-13 | — | Amryt Pharmaceuticals Designated Activity Company |
Octreotide (acetate) | small molecules | FDA | 2022-06-30 | — | Chiesi USA, Inc. |
telotristat etiprate [Xermelo] | small molecules | FDA | 2012-03-09 | 2017-02-28 | TerSera Therapeutics, LLC |
lanreotide acetate | peptides | FDA | 2011-09-08 | 2017-09-15 | Ipsen Biopharmaceuticals, Inc. |
(S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate [Xermelo] | small molecules | EMA | 2009-10-08 | 2017-09-20 | Serb |
Vapreotide | peptides | FDA | 2004-04-06 | — | H3 Pharma, Inc. |
Octreotide [Sandostatin LAR] | peptides | FDA | 1998-08-24 | 1998-11-25 | Novartis Pharmaceuticals Corporation |
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