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 2 000 pg/ml, and blood CEA level of 70.8 μg/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 446.61 μg/L, respectively. The 24-hour urine free cortisol measurement was 1 200 μg, 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 538.27 μg/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 18F-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. Results:The 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 100 μg 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.