Iwayama Hideyuki, Hirase Sho, Nomura Yuka, Ito Tatsuo, Morita Hiroyuki, Otake Kazuo, Okumura Akihisa, Takagi Junko
Department of Paediatrics, Aichi Medical University, School of Medicine, Nagakute, Japan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Aichi Medical University, School of Medicine, Nagakute, Japan.
BMC Endocr Disord. 2018 Mar 27;18(1):19. doi: 10.1186/s12902-018-0246-2.
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition.
A 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1 μg/dL; 6.4-21.0 μg/dL) and 24-h urinary free cortisol (UFC) (6160 μg/day; 11.2-80.3 μg/day) levels. Chest computed tomography identified a solid 26.6 × 22.9 × 30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL; highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce cortisol production. ACTH levels and cortisol and UFC levels were normalised and the ACTH-producing lung tumour was ablated after MTP treatment. In several reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of thymic carcinoid and one of islet cell carcinoma were reported. In four cases, the tumour was not detected. In our case, the pathology of the lung tumour was unknown because of lack of tumour cells in biopsy. The patients were treated with ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression, but tumour regression was observed only in our case.
MTP and/or KTZ may reduce ACTH and cortisol production. The tumour spontaneously regressed after MTP treatment, indicating that MTP may reduce the tumour size without surgery. The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis of spontaneous remission should be elucidated further via molecular biology studies.
异位促肾上腺皮质激素（ACTH）综合征（EAS）由释放ACTH的肿瘤引起。使用类固醇生成抑制剂很少能诱导异位产生ACTH的肿瘤消退。我们报告了1例EAS病例，其中甲吡酮（MTP）降低了肺肿瘤产生的ACTH，并回顾了以往通过抑制类固醇生成来抑制异位ACTH产生的病例。
一名71岁女性，有全身乏力、向心性肥胖和糖耐量受损，因ACTH（192.9 pg/mL；正常范围7.2 - 63.3 pg/mL）、皮质醇（73.1 μg/dL；6.4 - 21.0 μg/dL）和24小时尿游离皮质醇（UFC）（6160 μg/天；11.2 - 80.3 μg/天）水平升高而被诊断为库欣综合征。胸部计算机断层扫描发现左肺上叶有一个实性的26.6×22.9×30.0 mm肿瘤，有一个空洞。肾上腺无增大。肿瘤标志物无明显升高；8 mg地塞米松未抑制ACTH水平。促肾上腺皮质激素释放激素刺激试验显示ACTH反应迟钝（基础ACTH，204.6 pg/mL；120分钟刺激试验期间最高ACTH水平，214.0 pg/mL）。她因肺部病变被诊断为EAS。开始MTP治疗以减少皮质醇产生。MTP治疗后ACTH水平以及皮质醇和UFC水平恢复正常，产生ACTH的肺肿瘤被消融。在一些报道的病例中，EAS患者在使用类固醇生成抑制剂治疗期间血浆ACTH水平降低。在这10例患者中，报告了3例嗜铬细胞瘤、1例胸腺类癌和1例胰岛细胞癌。在4例中未检测到肿瘤。在我们的病例中，由于活检中缺乏肿瘤细胞，肺肿瘤的病理情况不明。这些患者接受了酮康唑（KTZ）和/或MTP治疗，ACTH和皮质醇/UFC受到抑制，但仅在我们的病例中观察到肿瘤消退。
MTP和/或KTZ可能会减少ACTH和皮质醇的产生。MTP治疗后肿瘤自发消退，表明MTP可能无需手术即可缩小肿瘤大小。类固醇生成抑制剂的治疗作用机制和自发缓解的预后应通过分子生物学研究进一步阐明。
