Pathogenesis (disease development)
Pheochromocytoma is a neuroendocrine (affecting the nervous system) catecholamine-producing tumor of the chromaffin cells of the adrenal medulla (85% of cases) or sympathetic ganglia (nerve cord that runs along the spine in the thoracic (chest) and abdominal (stomach) regions) (15% of cases). The latter is also called extraadrenal (outside the adrenal gland) pheochromocytoma or paraganglioma.
Pheochromocytomas produce catecholamines. Two-thirds of pheochromocytomas secrete (release) norepinephrine and epinephrine, while extraadrenally located tumors above the diaphragm (diaphragm) produce only norepinephrine. Malignant (malignant) pheochromocytomas also produce dopamine. Due to the excess of catecholamines, hypertensive crises (high blood pressure crises; blood pressure values > 230/120 mmHg) occur. A pheochromocytoma is found in approximately 0.1-0.5% of all hypertensions.
Pheochromocytoma may be sporadic (with no apparent cause; approximately 75% of cases) or familial. In approximately one-third of cases, a genetic cause underlies the pheochromocytoma (see below)
Etiology (Causes)
Biographic causes
- Genetic burden from parents, grandparents – in 25-30% of cases.
Pheochromocytoma may be associated with the following genetic diseases:
- Multiple endocrine neoplasia (MEN), type 2a – genetic disorder leading to various benign (benign) and malignant (malignant) tumors; commonly affects the thyroid, adrenal medulla, and parathyroid glands
- Neurofibromatosis – genetic disease with autosomal dominant inheritance; belongs to the phakomatoses (diseases of the skin and nervous system); three genetically different forms are distinguished:
- Neurofibromatosis type 1 (von Recklinghausen’s disease) – patients develop multiple neurofibromas (nerve tumors) during puberty, which often occur in the skin but also occur in the nervous system, orbita (eye socket), gastrointestinal tract (gastrointestinal tract), and retroperitoneum (space located behind the peritoneum on the back toward the spine); Typical is the appearance of café-au-lait spots (light brown macules) and multiple benign (benign) neoplasms
- [Neurofibromatosis type 2 – characteristic is the presence of bilateral (bilateral) acoustic neuroma (vestibular schwannoma) and multiple meningiomas (meningeal tumors).
- Schwannomatosis – hereditary tumor syndrome]
- Paraganglioma syndrome (mutations of succinate dehydrogenase B/C/D).
- Von Hippel-Lindau syndrome (VHL; synonym: retino-cerebellar angiomatosis); genetic disease with autosomal dominant inheritance from the group of forms known as phakomatoses (group of diseases with malformations in the skin and nervous system); symptoms: benign angiomas (benign vascular malformations), mainly in the retina (retina) and cerebellum.
