Koehler Viktoria F, Fuss Carmina T, Berr Christina M, Frank-Raue Karin, Raue Friedhelm, Hoster Eva, Hepprich Matthias, Christ Emanuel, Pusl Thomas, Reincke Martin, Spitzweg Christine, Kroiss Matthias
Department of Internal Medicine IV, LMU Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.
Department of Medicine I, Goethe University Hospital, Frankfurt, Germany.
Clin Endocrinol (Oxf). 2022 Jun;96(6):847-856. doi: 10.1111/cen.14617. Epub 2021 Nov 6.
Ectopic Cushing's syndrome (ECS) induced by medullary thyroid cancer (MTC) is rare, and data on clinical characteristics, treatment and outcome are limited.
Retrospective cohort study in three German and one Swiss referral centres.
Eleven patients with MTC and occurrence of ECS and 22 matched MTC patients without ECS were included.
The primary endpoint of this study was the overall survival (OS) in MTC patients with ECS versus 1:2 matched MTC patients without ECS.
The median age at diagnosis of ECS was 59 years (range: 35-81) and the median time between initial diagnosis of MTC and diagnosis of ECS was 29 months (range: 0-193). Median serum morning cortisol was 49 µg/dl (range: 17-141, normal range: 6.2-18). Eight (73%) patients received treatment for ECS. Treatment of ECS consisted of bilateral adrenalectomy (BADX) in four (36%) patients and adrenostatic treatment in eight (73%) patients. One patient received treatment with multityrosine kinase inhibitor (MKI) to control hypercortisolism. All patients experienced complete resolution of symptoms of Cushing's syndrome and biochemical control of hypercortisolism. Patients with ECS showed a shorter median OS of 87 months (95% confidence interval [95% CI]: 64-111) than matched controls (190 months, 95% CI: 95-285). Of the nine deaths, four were related to progressive disease (PD). Four patients showed PD as well as complications and comorbidities of hypercortisolism before death.
This study shows that ECS occurs in advanced stage MTC and is associated with a poor prognosis. Adrenostatic treatment and BADX were effective systemic treatment options in patients with MTC and ECS to control their hypercortisolism. MKI treatment achieved complete remission of hypercortisolism and sustained tumour control in one treated case.
甲状腺髓样癌（MTC）所致异位库欣综合征（ECS）较为罕见，关于其临床特征、治疗及预后的数据有限。
在三个德国和一个瑞士转诊中心进行的回顾性队列研究。
纳入11例发生ECS的MTC患者以及22例匹配的未发生ECS的MTC患者。
本研究的主要终点是发生ECS的MTC患者与1:2匹配的未发生ECS的MTC患者的总生存期（OS）。
ECS诊断时的中位年龄为59岁（范围：35 - 81岁），MTC初始诊断至ECS诊断的中位时间为29个月（范围：0 - 193个月）。清晨血清皮质醇中位数为49µg/dl（范围：17 - 141，正常范围：6.2 - 18）。8例（73%）患者接受了ECS治疗。ECS的治疗包括4例（36%）患者接受双侧肾上腺切除术（BADX），8例（73%）患者接受肾上腺抑制治疗。1例患者接受多酪氨酸激酶抑制剂（MKI）治疗以控制高皮质醇血症。所有患者库欣综合征症状均完全缓解，高皮质醇血症得到生化控制。发生ECS的患者中位OS为87个月（95%置信区间[95%CI]：64 - 111），短于匹配对照组（190个月，95%CI：95 - 285）。9例死亡患者中，4例与疾病进展（PD）相关。4例患者在死亡前出现PD以及高皮质醇血症的并发症和合并症。
本研究表明，ECS发生于晚期MTC，且预后不良。肾上腺抑制治疗和BADX是MTC合并ECS患者控制高皮质醇血症的有效全身治疗选择。在1例接受治疗的病例中，MKI治疗实现了高皮质醇血症的完全缓解并持续控制肿瘤。
