Carcinoid syndrome E34.0

Lubarsch, 1888; Oberndorfer, 1907

Metastasized tumor, usually localized in the lower ileum, endocrine active, originating from the cells of the APUD system, characterized by a seizure-like flush symptomatology.

Most common endocrine disease of the gastrointestinal tract. Incidence: 0.3-0.5/100.000 diseases/year.

Production of serotonin and other biologically active substances (histamine, VIP, prostaglandins, glucagon, gastrin, calcitonin) by the enterochromaffin cells proliferating in the carcinoid.

Women and men are equally affected, mainly in the 2nd-7th decade.

Integument: Flushing symptoms associated with episodes of itching, triggered by vasoactive procedures and substances (emotional arousal, hot soups, spicy foods, alcohol, salicylic acid, acetaminophen, methocarbamol, mephenesin). In cases of recurrent symptoms, diffuse cyanosis of the face and neck, telangiectasias, and periorbital swelling may occur. Pellagra-like manifestations, including xerosis, hyperkeratosis, and scaling on the neck and forearms, develop when the endocrine-active substances secreted by carcinoid cells—such as serotonin, histamine, kinins, and prostaglandins—become systemically active due to the loss of hepatic inactivation, usually following liver metastasis.

Extracutaneous manifestations:

• Abdomen: Periodic abdominal pain, diarrhea, nausea, vomiting
• Heart: Thickening and shrinkage of the pulmonary and tricuspid valves as well as the endocardium = endocarditis fibroplastica; signs of acquired (primarily right-sided) valvular heart disease (tricuspid insufficiency and pulmonary stenosis), tachycardia, hypotensive crises, and asthma-like symptoms. On the ECG: low voltage, right atrial overload, right ventricular hypertrophy, and right bundle branch block. During a carcinoid flush, coronary spasms with Prinzmetal angina may occur 
• Pulmonary signs: Bronchial asthma. Metabolic signs: including bouts of ravenous hunger with spontaneous hypoglycemia.

Detection of increased hormone production. Detection of increased excretion of 5-hydroxy-indoleacetic acid in urine in about 30% of patients (more than 20 mg/24 hrs). For insulinoma in particular: 72-hour hunger test with determination of blood sugar, plasma insulin level and C-peptide. With mainly gastrinoma: gastrin test.

Tumour from argentophilic cells (argentaffinoma).

Conservative therapy for inoperable tumors or metastases: First-line therapy: the somatostatin analog octreotide (e.g., Sandostatin). Initially, 50 µg of octreotide subcutaneously 1–2 times daily. Subsequently, dose escalation to 100–200 µg subcutaneously 3 times daily.

Second-line therapy: Interferon alfa-2a (e.g., Roferon) 3 times per week, 3–6 million IU subcutaneously, or polychemotherapy (streptozocin, 5-fluorouracil, cyclophosphamide, doxorubicin).

Treatment of accompanying symptoms:

• Flushing: Kallikrein secretion: Receptor blockers such as phenoxybenzamine (e.g., Dibenzyran) 10–60 mg/day p.o.
• Histamine secretion: Clemastine (e.g., Tavegil) 1–2 mg/day p.o. or try_{H1 blockers}(e.g., diphenhydramine) in combination with_{H2 blockers}(e.g., ranitidine or cimetidine) 3 times/day mg p.o.
• Serotonin secretion: Cyproheptadine (e.g., Peritol) 6–30 mg/day p.o.
• Diarrhea: Loperamide (e.g., Imodium) 1 capsule twice daily or Tinctura opii simplex 10–20 drops three times daily, taken orally
• Pellagra-like symptoms: Nicotinamide (e.g., Nicobion) 200 mg/day by mouth or nicotinic acid (e.g., Niconacid) 250 mg/day by mouth.

Surgical removal of the primary tumour (usually partial resection of the small intestine) and the regional lymph nodes as early as possible, limited chances of success with a tumour size of > 2 cm.

Five-year survival rate: 18%. Mean survival time: 2.5 years. Disease progressions of up to 20 years were observed.

Low serotonin diet (avoid bananas, walnuts, tomatoes, pineapple, plums, mirabelle plums, melons, avocados, eggplants, kiwis and alcohol).

The term carcinoid, although well established in medical terminology, is no longer sufficient to cover the entire morphological and biological spectrum of neoplasias of the disseminated neuroendocrine cell system.

The WHO classification of 2000 therefore uses the superordinate terms neuroendocrine tumour (NET) and neuroendocrine carcinoma (NEK) instead of the term carcinoid.

In detail, a distinction is made between neuroendocrine tumours with benign behaviour, questionable dignity, low-malignant behaviour and high-malignant behaviour in relation to their localisation and based on various morphological and biological criteria.

S.u. Neuroendocrine tumors of the gastroentero-pancreatic system (GEP-NET)

1. Boushey RP et al (2002) Carcinoid tumors. Curr Treat Options Oncol 3: 319-326
2. Creutzfeldt W, Stöckmann F (1987) Carcinoid and Carcinoid Syndromes. On J Med 82: 4-16
3. Feldman JM (1987) Carcinoid tumors and syndrome. Semin Oncol 14: 237-249
4. Goede AC et al (2003) Carcinoid tumour of the appendix. Br J Surg 90: 1317-1322
5. Kähler HJ, Heilmeyer L (1961) Clinic and pathophysiology of carcinoid and carcinoid syndrome. Results Inn Med Pediatrics 16: 292-559
6. Lubarsch O (1888) On the primary cancer of the ileum together with remarks on the simultaneous occurrence of cancer and tuberculosis. Virchows Arch path Anat 111: 280-317
7. Moller JE et al (2003) Factors associated with progression of carcinoid heart disease. N Engl J Med 348: 1005-1015
8. Oberndorfer S (1907) Carcinoid tumors of the small intestine. Frankf Z Pathol 1: 425-429
9. Rodriguez J et al (2003) Combined typical carcinoid and acinic cell tumor of the lung: a heretofore unreported occurrence. Hum Pathol 34: 1061-1065