Summary Of Clinical Features Of Patients With Ectopic ACTH Syndrome

Objective We retrospectively analyzed the clinical data of 159 patients with ectopic ACTH syndrome,including 13 cases in our hospital and 146 cases published in China.We summarized the clinical characteristics of ectopic ACTH syndrome patients to improve the ability of diagnosis and treatment.Methods The article retrospectively analyzed 13 patients with ectopic ACTH syndrome from January 2008 to January 2019 in our hospital and combined with the clinical data of146 ectopic ACTH syndrome patients published in China from January 2009 to January2019.We also summarized the clinical characteristics of the 159 cases.Results The 13 ectopic ACTH syndrome patients in our hospital had hypokalemia,hypertension and typical manifestations of Cushing’s syndrome including full moon-shaped face,buffalo hump,central obesity,edema,sanguineous appearance and etc.7 cases of them had diabetes.The serum ACTH levels of 13 patients were 58.6± 47.9pmol/l.Serum cortisol levels and 24-hour urinary free cortisol significantly increased.The circadian rhythm of serum cortisol were disappeared.The low-dose dexamethasone suppression test（LDDST）could not be inhibited.11 cases of them underwent high-dose dexamethasone suppression test（HDDST）and 10 cases（90.9%）could not be inhibited.Bilateral inferior petrosal sinus sampling（BIPSS）were performed in 6 patients,the ratio of ACTH in inferior petrosal sinus/peripheral venous were 1.05±0.27,all of which were less than 2.0.The results of pituitary magnetic resonance examination of 13 patients were normal.The results of adrenal CT examination showed bilateral adrenal thickening in 4cases（30.8%）,left adrenal enlargement in 3 cases（23.0%）,left adrenal nodule in 1 case（7.7%）,right adrenal space occupying lesion,possible adenoma in 1 case（7.7%）and normal in 4 cases（30.8%）.11 patients underwent chest CT examination,5 cases（45.5%）presented mediastinal soft tissue nodules,which were considered as neoplastic lesions,thymoma or thymic hyperplasia,2 cases（18.2%）showed pulmonary soft tissue nodules,which were considered as neoplastic lesions,and 1 cases（9.1%）indicated infectious lesions.The results of epigastrium MRI or CT indicated that 2 patients had pancreatic tumor.2 patients underwent ¹⁸FDG-PET/CT examination and 1 patient presented mediastinal lesion.1 patient received ⁶⁸Ga-DOTATATE-PET/CT showing small anterior mediastinal nodules and plump pancreas tail.8 patients underwent surgery.4 cases were thymus carcinoid and 1 case was highly differentiated endocrine carcinoma of the pancreas head.Immunohistochemical staining showed that chromotropin A（Cg A）,CD56 and synaptophysin（Syn）were positive in 6 patients,and ACTH were positive in 2 patients.Of the 13 patients,3 cases（23.1%）died,3 cases（23.1%）lost to follow up,and 7 cases（53.8%）were still alive.We retrospected ectopic ACTH syndrome patients’clinical data of 13 cases and 146 cases published in China.The clinical manifestation included hypokalemia in 154cases（96.9%）,hypertension in 142 cases（89.3%）,hyperglycemia in 128 cases（80.5%）, moon face in 118 cases（74.2%）,buffalo hump in 114 cases（71.7%）,centrality obesity in114 cases（71.7%）,sanguineous appearance in 106 cases（66.7%）,and purple striae in 70cases（44.0%）.The level of ACTH were from 14.5 to 365.6pmol/l in 159 patients.Serum cortisol were much higher than the normal level and the circadian rhythm disappeared.The24-hour urinary free cortisol in 124 patients were higher than the normal range.156 patients underwent LDDST,and 156 cases（100%）were not inhibited.156 patients had HDDST and 153 cases（98.1%）could not be inhibited.43 patients（27.0%）underwent inferior petrosal sinus vein blood sampling（BIPSS）,the ACTH ratio of inferior petrosal sinus/peripheral（IPS/P）were less than 2.Pituitary MRI were performed in 159 patients,20cases（12.6%）showed the possibility of pituitary microadenoma.Adrenal CT examination were performed in 154 patients with adrenal hyperplasia in 135 cases（87.7%）,adrenal space-occupying lesions in 2 cases（1.3%）and adrenal nodules in 3 cases（1.9%）.Chest CT examination were performed in 148 patients.There were space occupying lesions of the lung in 48 cases（32.4%）,mediastinal space occupying lesions in 43 cases（29.1%）an inflammatory changes in 8 cases（5.4%）.Abdominal CT or MRI examination were performed in 80 patients,and pancreatic neoplastic lesions were found in 8 cases（10.0%）. 1 patient was thyroid tumor by cervical MRI.26 cases underwent PET/CT,19 cases（73.1%）were found significant radioactivity uptake of the lesions.Octreotide imaging was performed in 5 patients,3 patients（60.0%）were positive of the octreotide uptake.76 cases（47.8%）underwent tumor resection,including 33 cases（43.4%）of mediastinal carcinoid,26 cases（34.2%）of lung cancer,8 cases（10.5%）of pancreatic carcinoid,3 cases（3.9%）of paraganglioma,3 cases（3.9%）of lipoma,2 cases（2.6%）of medullary thyroid carcinoma and 1 case（1.3%）of primary liver cancer.Immunohistochemical examination were performed in 35 patients.Synaptophysin（Syn）were positive in 31 cases,CD56 were positive in 13 cases,ACTH were positive in 18 cases,Cg A were positive in 19 cases, neuron enolase（NSE）were positive in 19 cases,thyroglobulin（Tg）were positive in 1 case and calcitonin were positive in 1 case.27 patients underwent unilateral or bilateral adrenalectomy.Postoperative pathology showed adrenocortical hyperplasia.Patients with bilateral adrenal adrenalectomy were treated with corticosteroid replacement therapy.17patients chose medication.16 patients chose chemotherapy alone or radiotherapy plus chemotherapy.23 patients gave up treatment because of tumors progression or economic reasons.Of the 159 patients,42 cases（26.4%）died,43cases（27.0%）were lost to follow up and 74 cases（46.5%）were alive.Conclusion 1.The most common causes of ectopic ACTH syndrome are neuroendocrine tumors,including lung carcinoid,small cell lung cancer,thymic carcinoid,pancreatic neuroendocrine tumor,medullary thyroid carcinoma,pheochromocytoma and et al.Clinical characteristic shows hypokalemia,hypertension and Cushing’s syndrome.When the tumor progresses rapidly,Cushing’s syndrome may not obvious.2.The diagnosis of ectopic ACTH syndrome is difficult.Inferior petrosal sinus vein blood sampling（BIPSS）is the gold standard for the diagnosis of ectopic ACTH syndrome.3.It is difficult to locate the occult tumor in ectopic ACTH syndrome patients by conventional imaging methods.Octreotide SPECT imaging and ⁶⁸Ga-DOTA-octreotide PET imaging are recommended.4.Surgical treatment is the best therapy for ectopic ACTH syndrome patients with affirmed tumor and long term follow-up after operation is necessary.