What are common comorbidities of Carcinoid (Neuroendocrine) Syndrome?

From the Guidelines

Carcinoid syndrome is commonly associated with comorbidities such as carcinoid heart disease, diarrhea, malnutrition, psychiatric conditions, and other endocrine disorders, which significantly impact quality of life and require comprehensive management. These comorbidities can be attributed to the secretion of various hormones and vasoactive peptides by neuroendocrine tumors (NETs) of the gastrointestinal tract and lungs, as noted in the guidelines for the management of gastroenteropancreatic neuroendocrine tumors 1. Some key comorbidities include:

• Carcinoid heart disease (CHD), which affects up to 20% of patients with carcinoid syndrome, primarily involving right-sided heart valve damage due to serotonin exposure 1
• Diarrhea and malnutrition, leading to electrolyte imbalances and vitamin deficiencies, particularly niacin deficiency (pellagra)
• Psychiatric conditions such as anxiety and depression, due to both the physiological effects of hormone dysregulation and the psychological burden of living with a chronic condition
• Bronchospasm and asthma-like symptoms, particularly during carcinoid crisis
• Bone metastases, leading to osteoporosis and pathological fractures
• Fibrosis of the mesentery, retroperitoneum, and pleura, due to prolonged exposure to serotonin and other tumor-secreted factors
• Other endocrine disorders, including Cushing's syndrome, acromegaly, and hypercalcemia, as mentioned in the guidelines for neuroendocrine tumors 1. It is essential to consider these comorbidities when managing patients with carcinoid syndrome to improve their quality of life and overall prognosis.

From the Research

Common Comorbidities of Carcinoid Syndrome

• Carcinoid heart disease, which is characterized by fibrous endocardial plaques in the heart, is a common comorbidity of carcinoid syndrome, detected by echocardiography in over 50% of patients with this syndrome 2
• Right-sided valvular heart disease, involving most commonly the tricuspid and pulmonary valves, is a frequent comorbidity of carcinoid syndrome 2, 3
• Other comorbidities associated with carcinoid syndrome include:
  • Mesenteric and retroperitoneal fibrosis 4, 5
  • Venous telangiectasia 4
  • Dyspnea 4, 3
  • Fatigue 3
  • Right-sided heart failure 3, 6
  • Metastatic carcinoid disease 6

Pathophysiology of Comorbidities

• The pathophysiology of carcinoid heart disease is related to vasoactive substances secreted by the tumor, of which serotonin is most prominent in the pathophysiology of CHD 3
• Serotonin stimulates fibroblast growth and fibrogenesis, which can lead to cardiac valvular fibrosis 3
• The secretion of several humoral factors, including serotonin, histamine, kallikrein, prostaglandins, and tachykinins, contributes to the development of comorbidities associated with carcinoid syndrome 5