腹腔镜同期双侧肾上腺切除术治疗甲状腺髓样癌致异位ACTH综合征1例报告并文献复习

Ectopic ACTH hormone syndrome caused by medullary thyroid carcinoma treated by laparoscopic simultaneous bilateral adrenalectomy:a case report and literature review

目的按探讨腹腔镜同期双侧肾上腺切除术(BA)治疗甲状腺髓样癌(MTC)致异位促肾上腺皮质激素综合征(EAS)的安全性和疗效。方法患者男,56岁,2023年10月5日因MTC术后15个月,全身乏力7个月入院。既往因MTC行两次甲状腺开放手术。病理诊断:甲状腺髓样癌合并上纵隔、纵隔等处淋巴结转移,CRH(-)、ACTH(胞质弱+)。患者术后出现糖尿病、高血压、低钾血症。入院查体:血压200/95mmHg(1mmHg=0.133kPa),体质量61.5kg,身高160cm,体质量指数24.02kg/cm^(2),腰围83cm,多血质外貌,皮肤变薄。实验室检查:血钾2.71mmol/L,血钙1.47mmol/L,甲状旁腺素6.0pg/ml,空腹血糖10.51mmol/L,糖化血红蛋白8.2%,血降钙素>2000pg/ml,癌胚抗原70.8μg/L。内分泌激素检查:8:00、16:00、24:00时血浆ACTH分别为189.0、125.0、65.0pg/ml;8:00、16:20、24:00时血清皮质醇分别为429.30、408.14、446.61μg/L;24h尿游离皮质醇1200μg/24h;1mg过夜地塞米松抑制试验后8:00时ACTH183.0pg/ml、皮质醇538.27μg/L;非卧位2h醛固酮8.2pg/ml;血、尿儿茶酚胺和甲状腺功能均未见明显异常。^(18)F-FDG-PET/CT检查示颈部等多发淋巴结转移。腹部CT检查示双侧肾上腺增生。垂体增强MR检查示垂体变薄。肺CT、痰培养检查示双肺散在多发感染。经全院多学科讨论,诊断为EAS、MTC术后转移、糖尿病、高血压病、低钾血症、肺部感染、轻度贫血、肝功能不全、甲状旁腺功能减退症、低钙血症。全麻下行经腹腔入路腹腔镜BA。术中先切除左侧肾上腺,翻转体位,再切除右侧肾上腺。结果本例手术顺利。手术时间约60min。术中出血量约20ml。围术期未发生并发症。病理检查:(双侧)肾上腺皮质结节性增生;(双侧)肾上腺髓质增生,ACTH(-)。术后随访3个月,血降钙素仍>2000pg/ml。术后1周,以及1、3个月血ACTH分别为183.0、220.0、731.0pg/ml。但高血压、糖尿病、低钾血症等均迅速缓解。术后1个月血压100/80mmHg,空腹血糖4.4mmol/L,血钾3.87mmol/L;肺部感染好转。未发生肾上腺危像。糖皮质激素替代治疗方案:氢化可的松晨起20mg、午后10mg。甲状腺激素替代治疗方案:左甲状腺素100μg每日1次。基因检测示Ret基因杂合突变,患者应用Ret抑制剂临床试验性治疗。结论对于无法根治的MTC转移病灶导致的EAS,采取腹腔镜同期BA是安全、有效的,可纠正高血压、糖尿病和低钾血症,增加了MTC的治疗机会。

Objective To investigate the safety and efficacy of laparoscopic simultaneous bilateral adrenalectomy in treating ectopic ACTH syndrome(ACTH)caused by medullary thyroid carcinoma(MTC).Methods A 56-year-old male patient was admitted after MTC surgery and 7 months of general fatigue.The patient had a history of two open thyroid surgeries for medullary thyroid carcinoma,with previous pathological reports indicating lymph node metastasis in the upper mediastinum and mediastinum,accompanied by weak cytoplasmic expression of ACTH and negative CRH staining.After the operation,the patient developed diabetes,hypertension,and hypokalemia.Upon admission,the patient presented with a blood pressure reading of 200/95 mmHg(1 mmHg=0.133 kPa),a weight of 61.5 kg,a height of 160 cm,a body mass index(BMI)of 24.02 kg/cm^(2),and a waist circumference of 83 cm.Laboratory tests revealed the following:blood potassium level of 2.71 mmol/L,blood calcium level of 1.47 mmol/L,parathyroid hormone level of 6.0 pg/ml,fasting blood glucose level of 10.51 mmol/L,glycated hemoglobin level of 8.2%,blood calcitonin level exceeding 2000 pg/ml,and blood CEA level of 70.8μg/L.The plasma ACTH levels at 8:00,16:00,and 24:00 were 189.0,125.0,and 65.0 pg/ml,respectively.Serum cortisol levels at 08:00,16:00,and 24:00 were 429.30,408.14,and 446.61μg/L,respectively.The 24-hour urine free cortisol measurement was 1200μg,and after the midnight 1mg dexamethasone suppression test at 8:00,the plasma ACTH level was 183.0 pg/ml,and the serum cortisol level was 538.27μg/L.The aldosterone level in standing position after 2 hours was 8.2 pg/ml.There were no significant abnormality in catecholamine hormone detection or thyroid function in blood and urine samples.An ^(18)F-FDG-PET/CT examination showed multiple lymph node metastases in the neck,while an abdominal CT scan revealed bilateral adrenal hyperplasia.Enhanced MRI revealed pituitary gland thinning,and lung CT and sputum culture examinations showed scattered multiple lung infections.After a multidisciplinary discussion,the patient was diagnosed with EAS,postoperative MTC metastasis,diabetes,hypertension,hypokalemia,pulmonary infection,mild anemia,liver dysfunction,hypoparathyroidism,and hypocalcemia.The patient were accepted laparoscopic bilateral adrenalectomy via an abdominal approach under general anesthesia.The left adrenal gland was removed first,followed by the right adrenal gland after repositioning.ResultsThe surgery was successful with a surgical duration of approximately 60 minutes and an intraoperative bleeding volume of about 20 ml.No surgical complications occurred during the perioperative period.Pathological examination confirmed nodular hyperplasia of the adrenal cortex and bilateral adrenal medullary hyperplasia with negative ACTH staining.After a 3-month postoperative follow-up,blood calcitonin levels remained above 2000 pg/ml.The blood ACTH levels at 1 week,1 month,and 3 months after surgery were 183.0,220.0,and 731.0 pg/ml,respectively.However,hypertension,diabetes,and hypokalemia rapidly improved.One month after surgery,blood pressure was 100/80 mmHg,fasting blood glucose was 4.4 mmol/L,and blood potassium was 3.87 mmol/L.Pulmonary infection showed improvement,and no adrenal crisis occurred.Glucocorticoid replacement therapy consisted of 20 mg of hydrocortisone tablets in the morning and 10 mg in the afternoon,and thyroid hormone replacement therapy involved daily administration of 100μg of levothyroxine.Genetic testing revealed heterozygous mutations in the Ret gene.The patient is currently undergoing clinical trial treatment with Ret inhibitors.Conclusions Based on the data from this case and existing literature reports,laparoscopic simultaneous bilateral adrenalectomy might be safe and effective treatment option for EAS caused by unresectable MTC metastasis.It can correct hypertension,diabetes,and hypokalemia and increase the opportunity for MTC treatment.