Rizwan Azra, Sarfaraz Aqiba, Jabbar Abdul, Akhter Jaweed, Islam Najmul
Section of Endocrinology, Department of Medicine, Aga Khan University Hospital, Stadium Road, P,O, Box 3500, Karachi 74800, Pakistan.
BMC Endocr Disord. 2014 Jun 20;14:51. doi: 10.1186/1472-6823-14-51.
Cushing's syndrome results from exposure to excess glucocorticoids. Ectopic Cushings is endogenous ACTH dependant form of Cushing's associated with markedly raised ACTH and cortisol levels. This leads to an impaired immune response, setting the stage for occurrence of opportunistic infections. Nocardiosis is a gram positive bacterial infection caused by aerobic actinomycetes in genus Nocardia. We report a series of patients diagnosed with ectopic Cushings, having pneumonia with Nocardia spp. In one of these cases, the manifestations of Cushing's disappeared with treatment for Nocardia.
Two middle aged men of Asian descent presented to the Endocrine clinic: the first with history of exertional shortness of breath, and weight loss for 1 year, the other with facial swelling, disturbed sleep and lethargy for a month. The third case was a young Asian male who presented with progressive weakness & weight loss for 2 months. All three patients had uncontrolled hypertension, high blood sugars & were hypokalemic (K: 2.52, 2.9, 1.5 mmol/l); 24 hour urine cortisol was elevated at 2000, 27216 and 9088 (32-243 ug/24 hours); ACTH 68.5, 159, 255 [0-48 pg/ml), respectively. Their MRI pituitary was normal, inferior petrosal sinus sampling revealed no central peripheral gradient. CT chest of these subjects demonstrated cavitatory lung lesions; microscopic analysis of respiratory samples was suggestive of infection with Nocardia spp. Histopathology of bronchoscopic-guided biopsy revealed no malignancy. Antihypertensives, insulin, potassium replacement, ketoconazole & trimethoprim-sulphamethoxazole (TS) were initiated. The patients' symptomatology improved & cavitatory lesions resolved with treatment. The primary source for the ectopic cushings remained unknown. The first case required bilateral adrenalectomy. The second case followed a progressively downhill course leading to death. In the third case, we were able to completely taper off ketoconazole, potassium, insulin & antihypertensives, after starting TS.
Opportunistic infections are known to be associated with Cushing's syndrome, and higher levels of glucocorticoid secretion are found in patients with ectopically produced ACTH. Pulmonary nocardiosis is important differential to consider. This series includes the first case reported in which signs and symptoms of cushings subsided after treatment of Nocardia.
库欣综合征是由于长期暴露于过量糖皮质激素所致。异位库欣综合征是库欣综合征的一种内源性促肾上腺皮质激素依赖型，其促肾上腺皮质激素和皮质醇水平显著升高。这会导致免疫反应受损，为机会性感染的发生奠定基础。诺卡菌病是由诺卡菌属需氧放线菌引起的革兰氏阳性细菌感染。我们报告了一系列被诊断为异位库欣综合征且患有诺卡菌属肺炎的患者。在其中一例中，库欣综合征的症状在接受诺卡菌治疗后消失。
两名亚洲裔中年男性前往内分泌诊所就诊：第一名患者有劳力性气短和体重减轻1年的病史，另一名患者有面部肿胀、睡眠障碍和嗜睡1个月的病史。第三例是一名年轻的亚洲男性，出现进行性虚弱和体重减轻2个月。所有三名患者均患有未控制的高血压、高血糖且低钾血症（血钾分别为2.52、2.9、1.5 mmol/L）；24小时尿皮质醇升高，分别为2000、27216和9088（32 - 243 μg/24小时）；促肾上腺皮质激素分别为68.5、159、255[0 - 48 pg/ml]。他们的垂体MRI检查正常，岩下窦取样未发现中央外周梯度。这些患者的胸部CT显示有空洞性肺部病变；呼吸道样本的显微镜分析提示诺卡菌属感染。支气管镜引导下活检的组织病理学检查未发现恶性肿瘤。开始使用抗高血压药、胰岛素、补钾、酮康唑和甲氧苄啶 - 磺胺甲恶唑（TS）进行治疗。患者的症状有所改善，空洞性病变经治疗后消退。异位库欣综合征的原发部位仍然不明。第一例患者需要进行双侧肾上腺切除术。第二例患者病情逐渐恶化，最终死亡。在第三例患者中，开始使用TS后，我们能够完全停用酮康唑、钾、胰岛素和抗高血压药。
已知机会性感染与库欣综合征有关，异位产生促肾上腺皮质激素的患者糖皮质激素分泌水平更高。肺部诺卡菌病是需要考虑的重要鉴别诊断。本系列包括首例报道的诺卡菌治疗后库欣综合征的体征和症状消退的病例。
