Srirangalingam Umasuthan, Walker Lisa, Khoo Bernard, MacDonald Fiona, Gardner Daphne, Wilkin Terence J, Skelly Robert H, George Emad, Spooner David, Monson John P, Grossman Ashley B, Akker Scott A, Pollard Patrick J, Plowman Nick, Avril Norbert, Berney Daniel M, Burrin Jacky M, Reznek Rodney H, Kumar V K Ajith, Maher Eamonn R, Chew Shern L
Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK.
Clin Endocrinol (Oxf). 2008 Oct;69(4):587-96. doi: 10.1111/j.1365-2265.2008.03274.x. Epub 2008 Apr 14.
Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations.
Retrospective case-series.
Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres.
Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.
Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension.
SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.
嗜铬细胞瘤和副神经节瘤在高达25%的病例中具有家族性，可由琥珀酸脱氢酶（SDH）基因突变引起。本研究的目的是描述携带SDH - B基因突变患者的临床表现。
回顾性病例系列研究。
1975年至2007年期间对32例携带SDH - B基因突变的患者进行随访。平均随访5.8年（标准差7.4，范围0 - 31年）。患者来自伦敦圣巴塞洛缪医院及英国其他中心。
临床表现特征、基因突变、肿瘤位置、儿茶酚胺分泌、临床病程及治疗情况。
32例患者中有16例（50%）患病。发现SDH - B基因有两个此前未描述的突变。仅18%的索引患者有家族病史。诊断时的平均年龄为34岁（标准差15.4，范围10 - 62岁）。50%的患病患者在26岁时发病。69%（16例中的11例）患有高血压，80%（15例中的12例）儿茶酚胺/代谢产物分泌升高。24%（25例中的6例）的肿瘤位于肾上腺，76%（25例中的19例）位于肾上腺外。19%（16例中的3例）有多灶性病变。31%（16例中的5例）发生转移性副神经节瘤。1例患者发生转移性II型乳头状肾细胞癌。该队列的恶性肿瘤发生率为19%（32例中的6例）。在两名无高血压的患者中发现了大血管疾病。
携带SDH - B基因突变者发病较早，且主要发生在肾上腺外部位。疾病外显率不完全。转移性疾病较为突出，但发生率低于此前报道。临床表现可能包括乳头状肾细胞癌和大血管疾病。
