Endocrine Abstracts

Ectopic ACTH secreting syndrome is a rare cause of endogenous ACTH dependent Cushing syndrome. We aim to analyze clinical, biochemical, imaging profile, as well as management and outcomes of 7 EAS patients diagnosed in our clinic within the last 10 years, based on clinical presentation, hypercortisolism, high ACTH levels, specifically over 100pg/ml, with failed high dose dexamethasone suppression test. Clinical presentation was characteristic in 5 of the patients, but 2 showed no signs of Cushing syndrome. The common biochemical feature in 5 of 7 cases was severe, treatment-resistant hypokalemia. All patients also presented with or quickly developed classic complications like diabetes, hypertension, osteoporosis and fractures, recurrent bacterial infections and poor wound healing. A CT scan helped in identifying the causative lesions - 3 neuroendocrine tumors and 3 bronchopulmonary tumors. In one case, the primary tumor couldn’t be identified. In almost all cases, coincidental CT findings such as ovarian cystadenoma, adrenal lesions, or benign hepatic and pulmonary lesions, made identifying the primary lesion more difficult. Tektrotide scintigraphy was also necessary in two cases to identify the lesion and assess somatostatin receptor expression. While the therapeutic approach varies, resection of the primary tumor and metastases is the therapeutic goal. When impossible, therapeutic approach can range from steroidogenesis inhibitors such as ketoconazole, which were initiated in all cases, but were therapeutically inefficient or caused side effects (primarily alteration of liver function tests), which led to discontinuation of medication; but also somatostatin analogues, which we initiated both before and after scintigraphic confirmation of receptor expression. Palliative mytotane and osilodrostat therapy was also used to attempt disease control until surgical intervention. Ultimately, bilateral adrenalectomy was the only solution in 3 of the 7 cases. Of 7 cases, only one patient was cured following primary tumor resection one went through primary tumor resection and metastasectomy last week and is currently stable; while the others died within 1 month to 4 years since diagnosis because of sepsis, ischemic stroke or respiratory failure caused by primary bronchopulmonary tumor. In conclusion, ectopic ACTH secreting syndrome is a life-threatening condition, and management and outcome depend both on early diagnosis and prompt therapeutic intervention. The main challenges are identifying the primary lesion and managing the many associated comorbidities, such as hypertension, diabetes, electrolyte imbalances and recurrent infections. A multidisciplinary team comprising of endocrinologists, internal medicine specialists, infectious disease specialists and surgeons is mandatory for the best outcome of these patients.