The differential diagnosis and treatment of Cushing's syndrome

肺肿瘤异位促肾上腺皮质激素分泌引起库欣综合征与高发病率相关。最佳管理仍然模糊，因为知识是基于少数患者的罕见报告。对1982年至2020年的观察性病例系列进行了审查。参与者接受了肺神经内分泌肿瘤引起的库欣综合征的根治性手术。在68例患者中，中位年龄为41岁（范围：17-80岁），42.6%（29/68）为男性，81.8%（54/66）为白色，术后平均随访时间为16个月（范围：0.1-341个月）。肺叶切除术是最常见的手术（48/68 70.6%），其次是楔形切除术（16/68 23.5%）和肺段切除术（3/68 4.4%）。68例患者中有19例（27.9%）进行了电视辅助胸腔镜手术。手术并发症发生率为19.1%（13/68），围手术期死亡率为1.5%（1/68）。可评价时，淋巴结阳性率为37%（22/59）。持续性/复发的总体发生率为16.2%（11/68），至复发的中位时间为55个月（范围：18-152个月）。中位无病生存期为12.7年（0.1-334个月）。基于肿瘤大小、分期（第8版TNM）、是否进行全系统淋巴结切除术、淋巴结状态或手术方式，无病生存率无统计学差异。在本病例系列研究中，与静止期支气管肺类癌相比，与库欣综合征相关的肺神经内分泌肿瘤的淋巴结转移增加，复发率较高，DFS较低，但许多患者的结局良好。TNM分期与预后的不一致性强调了这一观察结果。在手术技术上没有观察到差异，这可能意味着保留肺的方法就足够了。这些结果可能反映了激素生理学而不是类癌生物学因素的内在重要性。 明确诊断库欣病（CD）仍然具有挑战性，但在推荐经蝶手术切除腺瘤之前至关重要。 我们回顾性分析了105例疑似CD患者的术前生化和影像学资料，以评估其是否可以预测术后缓解。患者分为3组：A组（n = 84）病理证实的ACTH腺瘤; B组（n = 6）病理未证实但术后低皮质醇血症与CD一致; C组（n = 15）病理未证实，术后无低皮质醇血症。合并A + B组为确诊CD组，C组为未确诊CD组。所有组具有相似的临床表型。与C组相比，A + B组的平均UFC（P < 0.001）、LNSC（P = 0.003）、DST（P = 0.06）和ACTH（P = 0.03）更高，MRI定义的病变更大（P < 0.001）。76/105例（72%）患者实现早期（3个月）生化缓解：A + B组与C组分别为76/90例（84%）和0/15例（0%），P < 0.0001。在A + B组中，未缓解与腺瘤海绵窦浸润密切相关。使用严格的生化阈值可能有助于避免对可疑数据的CD患者进行经蝶手术，并提高手术缓解率。具有库欣样表型但生化数据不明确的患者需要进行额外的严格检测。

Ectopic adrenocorticotropic hormone secretion from lung tumors causing Cushing syndrome is associated with high rates of morbidity. Optimal management remains obscure because knowledge is based on rare reports with few patients. An observational case series review from 1982 to 2020 was conducted. Participants underwent curative-intent surgery for a lung neuroendocrine tumor causing Cushing syndrome. Of the 68 patients, the median age was 41 years (range, 17-80 years), 42.6% (29 of 68) were male, 81.8% (54 of 66) were White, with a mean follow-up after surgery was 16 months (range, 0.1-341 months). Lobectomy was the most common procedure (48 of 68 70.6%), followed by wedge resection (16 of 68 23.5%) and segmentectomy (3 of 68 4.4%). Video-assisted thoracoscopic surgery was performed in 19 of 68 (27.9%) of patients. Surgical morbidity was 19.1% (13 of 68), and perioperative mortality was 1.5% (1 of 68). Lymph node positivity was 37% (22 of 59) when evaluable. The overall incidence of persistence/recurrence was 16.2% (11 of 68) with a median time to recurrence of 55 months (range, 18-152 months). The median disease-free survival was reached in 12.7 years (0.1-334 months). There were no statistical differences in disease-free survival based on tumor size, stage (8th edition TNM), whether full systematic lymphadenectomy was performed or not, nodal status, or surgical approach. In this case series study, neuroendocrine pulmonary tumors associated with Cushing syndrome had increased nodal metastasis, higher recurrence, and lower DFS than quiescent bronchopulmonary carcinoid tumors, but many patients experienced favorable outcomes. This observation is underscored by the discordance of TNM-stage classifications vs prognosis. Observing no difference in surgical techniques, the implication may be that a lung-sparing approach could suffice. These results may reflect the intrinsic importance of the hormone physiology instead of the carcinoid biologic factors. Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. We retrospectively reviewed the preoperative biochemical and imaging data in 105 patients with presumed CD to evaluate whether they could predict post-operative remission. Patients were classified into 3 groups: group A (n = 84) pathology-proven ACTH adenoma; group B (n = 6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (n = 15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (P < 0.001), LNSC (P = 0.003), DST (P = 0.06), and ACTH (P = 0.03) and larger MRI-defined lesions (P < 0.001). Early (3-month) biochemical remission was achieved in 76/105 (72%) patients: 76/90(84%) and 0/15(0%) of group A + B vs group C, respectively, P < 0.0001. In group A + B, nonremission was strongly associated with adenoma cavernous sinus invasion. Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.