Menon Ravi Kumar, Ferrau Francesco, Kurzawinski Tom R, Rumsby Gill, Freeman Alexander, Amin Zahir, Korbonits Márta, Chung Teng-Teng L L
Department of Endocrinology, University College Hospital NHS Foundation Trust , NW1 2PG, London , UK.
Centre for Endocrinology, Barts and the London School of Medicine, Queen Mary University of London , EC1A 7BE, London , UK.
Endocrinol Diabetes Metab Case Rep. 2014;2014:140074. doi: 10.1530/EDM-14-0074. Epub 2014 Nov 1.
Adrenal cortical carcinoma (ACC) has previously only been reported in eight patients with type 1 neurofibromatosis (NF1). There has not been any clear evidence of a causal association between NF1 gene mutations and adrenocortical malignancy development. We report the case of a 49-year-old female, with no family history of endocrinopathy, who was diagnosed with ACC on the background of NF1, due to a novel germline frame shift mutation (c.5452_5453delAT) in exon 37 of the NF1 gene. A left adrenal mass was detected by ultrasound and characterised by contrast computerised tomography (CT) scan. Biochemical tests showed mild hypercortisolism and androgen excess. A 24-h urinary steroid profile and (18)flouro deoxy glucose PET suggested ACC. An open adrenalectomy was performed and histology confirmed ACC. This is the first reported case with DNA analysis, which demonstrated the loss of heterozygosity (LOH) at the NF1 locus in the adrenal cancer, supporting the hypothesis of an involvement of the NF1 gene in the pathogenesis of ACC. LOH analysis of the tumour suggests that the loss of neurofibromin in the adrenal cells may lead to tumour formation.
ACC is rare but should be considered in a patient with NF1 and adrenal mass when plasma metanephrines are normal.Urinary steroid metabolites and PET/CT are helpful in supporting evidence for ACC.The LOH at the NF1 region of the adrenal tumour supports the role of loss of neurofibromin in the development of ACC.
肾上腺皮质癌（ACC）此前仅在8例1型神经纤维瘤病（NF1）患者中被报道过。目前尚无明确证据表明NF1基因突变与肾上腺皮质恶性肿瘤的发生存在因果关联。我们报告了一例49岁女性病例，该患者无内分泌疾病家族史，因NF1基因第37外显子的一种新的种系移码突变（c.5452_5453delAT），在NF1背景下被诊断为ACC。通过超声检测到左肾上腺肿块，并通过增强计算机断层扫描（CT）进行了特征性描述。生化检查显示轻度皮质醇增多症和雄激素过多。24小时尿类固醇谱和（18）氟脱氧葡萄糖PET提示为ACC。进行了开放性肾上腺切除术，组织学证实为ACC。这是首例进行DNA分析的病例，该分析显示肾上腺癌中NF1基因座存在杂合性缺失（LOH），支持了NF1基因参与ACC发病机制的假说。对肿瘤的LOH分析表明，肾上腺细胞中神经纤维瘤蛋白的缺失可能导致肿瘤形成。
ACC罕见，但当血浆甲氧基肾上腺素正常时，NF1患者出现肾上腺肿块应考虑ACC。尿类固醇代谢产物和PET/CT有助于支持ACC的证据。肾上腺肿瘤NF1区域的LOH支持神经纤维瘤蛋白缺失在ACC发生中的作用。
