Clinical Features and Prognosis of Patients with Carcinoid Syndrome and Carcinoid Heart Disease: A Retrospective Multicentric Study of 276 Patients

Abstract

Introduction: Carcinoid syndrome is the most frequent functional syndrome of neuroendocrine neoplasia. It is characterized by flushing, diarrhea, wheezing, hypotension, and exanthema and may cause carcinoid heart disease. Methods: We assessed clinical characteristics and prognosis of patients with carcinoid syndrome and carcinoid heart disease in 276 patients from 3 referral centers. Results: Carcinoid syndrome patients had a mean age of 57 years (range 21–84) and a normal BMI of 24.9 (SD 4.5; range 13.8–39.6). Most primaries were of small bowel or unknown primaries with distant metastasis in 94.6%. Flushing was the most frequent symptom in 74.3% of patients, followed by diarrhea in 68.8%, and wheezing in 40.9%. Pain was described by 45.3%, weakness by 23.5%, and weight loss of >10% in 6 months by 30.1% of patients. Carcinoid heart disease was diagnosed in 37.3% of patients (n = 104) by echocardiography and involved predominantly in the tricuspid valve. Combinations with other valve defects were common. Somatostatin analogs were taken by 80.4% of patients and 17% needed additional loperamide/opium tincture. Surgery and peptide receptor radiotherapy were most frequent treatments. The median survival of patients with carcinoid syndrome after diagnosis was 9 years. Prognosis was significantly impaired by male sex and diagnosis of carcinoid heart disease but surprisingly significantly increased by the presence of symptoms flushing and weakness. Discussion/Conclusion: Carcinoid syndrome is associated with extensive disease and primaries in small bowels or of unknown primary. Weight loss, weakness, and pain are frequent, and carcinoid heart disease is diagnosed in more than one-third of patients.

Outcome of carcinoid heart syndrome in patients enrolled in the SwissNet cohort

“…Survival rates of patients with CHD increased over a time period When excluding patients who received their diagnoses at end stage disease, the only significant parameter between patients with poor (average of 6 months) or long (average of 50 months) survival rates following initial CHD diagnosis was the time to CHD diagnosis following initial NET diagnosis. Similar findings were reported in a recently published study by Fijalkowski et al noting that CHD may not present with clinical symptoms in the beginning however echocardiographic valve alterations such as tricuspid insufficiency could be detected at an early time point during the course of disease leaving room for surgical interventions and prolonging survival [29]. Interestingly, tricuspid insufficiency was the most reported valve pathology in their and our cohort.…”

“…Interestingly, tricuspid insufficiency was the most reported valve pathology in their and our cohort. Therefore, evaluation of tricuspid insufficiency in patients with carcinoid syndrome could emerge as a new screening recommendation [ 29 ].…”

Carcinoid heart disease in patients with midgut neuroendocrine tumours

“…CHD is associated with a poor prognosis in patients with NETs 6,8,66 . In 1993, Pellikka et al 31 reported a 3‐year survival rate of 31% in patients with CS and CHD, compared with 68% in patients without CHD.…”

“…Since then, the prognosis of patients with CHD has gradually improved, with an increasing in median survival from 1–2 years in 2000 to 3–4 years in 2020 (Table 4). 7,17,19,55 Overall, recent studies have reported 1‐, 5‐ and 10‐year survival rates of approximately 70%, 35% and 20%, respectively, in patients operated on for CHD 6,17,48,51–55 …”

“…The main complication of CS is carcinoid heart disease (CHD) or Hedinger syndrome. It concerns 20%–35% of patients with CS and is associated with increased morbidity and mortality 4,6–8 . CHD represents a major diagnostic and therapeutic challenge in patients with NET and CS.…”