Neumann H P, Berger D P, Sigmund G, Blum U, Schmidt D, Parmer R J, Volk B, Kirste G
Department of Medicine, Albert-Ludwigs-Universität, Freiburg, Germany.
N Engl J Med. 1993 Nov 18;329(21):1531-8. doi: 10.1056/NEJM199311183292103.
Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance--multiple endocrine neoplasia type 2 (MEN-2) (with medullary thyroid carcinoma and hyperparathyroidism) and von Hippel-Lindau disease (with angioma of the retina, hemangioblastoma of the central nervous system, renal-cell carcinoma, pancreatic cysts, and epididymal cystadenoma). The frequency of these syndromes in patients with pheochromocytoma is not known.
In an unselected group of patients with pheochromocytoma, we performed pentagastrin tests, parathyroid hormone assays, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, ophthalmoscopy, CT imaging of the abdomen, and ultrasonography of the testes. We also screened members of families with MEN-2 or von Hippel-Lindau disease for pheochromocytoma by measuring plasma and urine catecholamines and plasma chromogranin A and by performing abdominal ultrasonography, CT and MRI, and metaiodobenzylguanidine scintigraphy.
Nineteen of 82 unselected patients with pheochromocytomas (23 percent) were carriers of familial disorders; 19 percent had von Hippel-Lindau disease and 4 percent had MEN-2. Prospectively, in 36 of 79 subjects at risk for pheochromocytoma (46 percent), 42 unsuspected pheochromocytomas were found. Overall, there were 130 patients with 185 pheochromocytomas; 43 had von Hippel-Lindau disease, 24 had MEN-2, and 63 had sporadic tumors. The patients with familial and those with sporadic pheochromocytomas differed in mean age at diagnosis (32 vs. 46 years, P < 0.001), multifocal localization (55 vs. 8 percent, P < 0.001), and cancer (0 vs. 11 percent, P = 0.005); but not in the frequency of extraadrenal tumors (24 vs. 16 percent). Thirty-eight percent of carriers of von Hippel-Lindau disease and 24 percent of carriers of MEN-2 had pheochromocytoma as the only manifestation of their syndrome.
All patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. All patients in families with MEN-2 or von Hippel-Lindau disease should be screened for pheochromocytoma, even if they are asymptomatic.
嗜铬细胞瘤是两种具有常染色体显性遗传模式的疾病的特征——2型多发性内分泌腺瘤病（MEN-2）（伴有甲状腺髓样癌和甲状旁腺功能亢进）和冯·希佩尔-林道病（伴有视网膜血管瘤、中枢神经系统血管母细胞瘤、肾细胞癌、胰腺囊肿和附睾囊腺瘤）。嗜铬细胞瘤患者中这些综合征的发生率尚不清楚。
在一组未经选择的嗜铬细胞瘤患者中，我们进行了五肽胃泌素试验、甲状旁腺激素测定、脑部计算机断层扫描（CT）或磁共振成像（MRI）、检眼镜检查、腹部CT成像和睾丸超声检查。我们还通过测量血浆和尿儿茶酚胺、血浆嗜铬粒蛋白A以及进行腹部超声检查、CT和MRI以及间碘苄胍闪烁显像，对患有MEN-2或冯·希佩尔-林道病的家族成员进行嗜铬细胞瘤筛查。
82例未经选择的嗜铬细胞瘤患者中有19例（23%）是家族性疾病携带者；19%患有冯·希佩尔-林道病，4%患有MEN-2。前瞻性研究发现，在79名有嗜铬细胞瘤风险的受试者中，有36名（46%）发现了42例未被怀疑的嗜铬细胞瘤。总体而言，有130例患者患有185个嗜铬细胞瘤；43例患有冯·希佩尔-林道病，24例患有MEN-2，63例患有散发性肿瘤。家族性嗜铬细胞瘤患者和散发性嗜铬细胞瘤患者在诊断时的平均年龄（32岁对46岁，P<0.001）、多灶性定位（55%对8%，P<0.001）和癌症（0对11%，P=0.005）方面存在差异；但在肾上腺外肿瘤的发生率方面无差异（24%对16%）。38%的冯·希佩尔-林道病携带者和24%的MEN-2携带者以嗜铬细胞瘤作为其综合征的唯一表现。
所有嗜铬细胞瘤患者均应筛查MEN-2和冯·希佩尔-林道病，以避免患者及其家族出现更多的发病和死亡情况。所有患有MEN-2或冯·希佩尔-林道病的家族中的患者均应接受嗜铬细胞瘤筛查，即使他们没有症状。
