Carcinoid syndrome

Syndrome substrate: carcinoid tumor

Diseases of the APUD system are called apudopathies, and tumors developing from it are called apudomas. Carcinoid is of the greatest clinical significance as it is the most frequent apudoma (accounting for over 55% of all neoplasms in this group).

Carcinoid is a polyendocrine neoplasm originating from enterochromaffin cells. Most commonly, the tumor is localized in the intestines (especially the appendix), pancreas, bronchi, and biliary tract.

Morphological features:

• Macroscopy: the tumor has a diameter of up to 2 cm, yellowish or whitish on cross-section.
• Microscopy: cells are monomorphic, round or polygonal. The cytoplasm is light, containing fine eosinophilic or brownish-red granularity. The nucleus is small, round in shape. Cellular structures form characteristic cords and nested complexes.

By the nature of its growth, it is a potentially malignant tumor. Its main feature is the secretion of biologically active substances. Serotonin is predominantly secreted, along with smaller amounts of bradykinin, 5-hydroxytryptophan, prostaglandins, vasoactive intestinal peptide, and histamine.

Clinical manifestations and the classic triad

The full-blown picture of the syndrome occurs due to the action of circulating mediators. Carcinoid syndrome is characterized by the classic triad:

1. Flushing of the face and upper torso.
2. Diarrhea (resulting from intestinal hypermotility).
3. Cardiovascular involvement.

In addition to the triad, systemic effects of mediators can provoke bronchospasm attacks, arthropathies, and impaired glucose tolerance. Patients also develop pellagra-like skin lesions. This symptom has an interesting pathogenesis: the tumor actively absorbs the amino acid tryptophan for large-scale serotonin synthesis, leading to a systemic deficiency of this amino acid in the body.

Carcinoid heart disease

Cardiovascular manifestations of carcinoid syndrome include angina attacks and hypertonic-type neurocirculatory dystonia. However, the most specific complication is carcinoid heart disease.

It develops as a result of the direct toxic action of serotonin. The right side of the heart is primarily affected, where milky-white carcinoid plaques form. Pronounced endocardial fibrosis develops, ultimately leading to a severe complication: tricuspid regurgitation. Similar plaques can be found in the tunica intima of large veins. The left side of the heart and the arterial bed are affected extremely rarely, as mediators are destroyed during passage through the lungs.

Microscopic examination of the myocardium reveals the following changes:

• slightly increased heart size;
• pronounced tissue edema;
• fatty degeneration of cardiomyocytes;
• small foci of necrosis;
• diffuse fine-focal cardiosclerosis.

Biochemical marker: 5-HIAA

Serotonin (5-hydroxytryptamine) is normally produced by chromaffin cells of the intestine and is also synthesized in the raphe nuclei of the central nervous system from tryptophan.

During metabolism, serotonin is degraded by the enzyme monoamine oxidase (MAO). The end product of this breakdown is 5-hydroxyindoleacetic acid (5-HIAA). In carcinoid tumors consisting of proliferating chromaffin tissue, serotonin secretion increases manifold. Consequently, a pathologically high concentration of 5-HIAA is recorded in the patients' urine, making this acid a reliable laboratory marker of carcinoid syndrome.

Class and exam questions

What else to study on this topic

• Multiple endocrine neoplasia (MEN): Wermer syndrome
• Synthesis and metabolism of dopamine, norepinephrine, and serotonin
• Dopamine hypothesis of schizophrenia and the role of homovanillic acid
• Mechanism of action of antipsychotics and drug-induced parkinsonism
• Monoamine theory of depression: the role of serotonin and norepinephrine

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