Pheochromocytoma: An update on genetics and management

Division of Endocrinology, Second Propedeutic Department of Internal Medicine, Medical School, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece.
Endocrine Related Cancer (Impact Factor: 4.91). 01/2008; 14(4):935-56. DOI: 10.1677/ERC-07-0142
Source: PubMed

ABSTRACT Pheochromocytomas (PHEOs) are rare neoplasms that produce catecholamines and usually arise from the adrenal medulla and are considered to be an adrenal paraganglioma (PGL). Closely related tumors of extraadrenal sympathetic and parasympathetic paraganglia are classified as extraadrenal PGLs. Most PHEOs are sporadic, but a significant percentage (approximately 25%) may be found in patients with germline mutations of genes predisposing to the development of von Hippel-Lindau disease, neurofibromatosis 1, multiple endocrine neoplasia type 1 (MEN1) and 2 (MEN2), and the PGL/PHEOs syndrome, based on the described mutations of the genes for succinate dehydrogenase subunit D (SDHD), B (SDHB), and C (SDHC). As one out of four PHEOs turns out to be a hereditary clinical entity, screening for genetic alterations is important, as it provides useful information for a rational diagnostic approach and management. This review discusses the genetics, the pathophysiology of hypertension, the clinical picture, the biochemical and imaging diagnosis, and the preferred therapeutic approach for PGLs/PHEOs. Furthermore, it emphasizes the need for genetic testing in cases with apparently sporadic PHEOs.

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    • "Type 2B is relatively uncommon, accounting for about 5 percent of all cases of multiple endocrine neoplasia and reported in approximately 1000 families worldwide in 2001. Men 2B is much less common but also more aggressive and is associated with medullary thyroid cancer (MTC), pheochromocytoma, multiple mucosal neuromas, gangliomatosis of gastrointestinal tract, and a marfanoid habitus, whereas hyperparathyroidism is absent [2] [3] [4] [5] [6] [7]. "
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    ABSTRACT: Multiple endocrine neoplasia type 2 (MEN2) is a rare familial syndrome caused by mutations in the RET protooncogene and it is transmitted as an autosomal dominant trait. The underlying problem for all the MEN syndromes is failure of a tumour suppressor gene. The genetic defect in MEN2 is on chromosome 10 (10q11.2) and has also been identified both for MEN2A and MEN2B. The reported patient is an 18-year-old girl presented with long-term diarrhea and enterocutaneous fistula. Her thyroid nodules, marfanoid habitus and bumpy lips, were also highly suggestive for MEN2B.
    Case Reports in Medicine 10/2012; 2012:491054. DOI:10.1155/2012/491054
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    • "The sporadic tumours rarely display somatic mutations in the genes associated with familial disease (Dannenberg et al. 2003). Most tumours are benign, but malignant pheochromocytomas have been reported to comprise up to 10% of all cases (Bravo & Tagle 2003, Elder et al. 2005, Karagiannis et al. 2007). Malignant tumours occur, however, more frequently among abdominal paragangliomas, representing w20% of these cases (Linnoila et al. 1990). "
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    ABSTRACT: Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (> or = 32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (> or = 14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
    Endocrine Related Cancer 09/2010; 17(3):561-79. DOI:10.1677/ERC-09-0310 · 4.91 Impact Factor
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    • "The classic clinical presentation is the triad of headache, palpitations, and diaphoresis. However, many cardiac symptoms are present, and the most common signs are labile hypertension and sinus tachycardia, secondary to high levels of circulating catecholamine [1]. Less frequently, the tumor can lead to myocardial dysfunction and cardiac failure, which is reversible after surgical treatment [2] [3] [4]. "
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    ABSTRACT: Pheochromocytoma is a catecholamine-secreting tumor of the adrenal glands, usually with benign manifestations, whose typical clinical presentation includes the triad of headache, palpitations and diaphoresis. However, a wide range of signs and symptoms may be present. In the cardiovascular system, the most common signs are labile hypertension and sinus tachycardia. Systolic heart failure and ST-segment deviations mimicking myocardial infarction have also been reported, as well as QT interval prolongation and, rarely, ventricular tachycardia. We describe a challenging diagnosis of pheochromocytoma with many cardiovascular manifestations, which could have been missed due to the absence of typical symptoms.
    Case Reports in Medicine 02/2010; 2010:976120. DOI:10.1155/2010/976120
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