Ectopic ACTH syndrome of different origin—Diagnostic approach and clinical outcome. Experience of one Clinical Centre

Abstract

Purpose Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5–20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production–especially neuroendocrine tumors with other neoplasms. Methods Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. Results Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. Conclusion EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

The usefulness of serum tumor markers for the differential diagnosis of ACTH-dependent Cushing’s syndrome

“…In the latest series from 2005 to 2020, the most frequent tumor marker in EAS was also serum calcitonin (44 to 69%), regardless of the tumor type, such as carcinoid tumors, small-cell lung cancer, pheochromocytoma, gastrinoma, ovarian carcinoma, occult tumors, and medullary thyroid cancer [8, [14][15][16][17].…”

Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization

“…[15] и 56,6±16,3 года в работе J. Paleń-Tytko и соавт. [16]. Определенную сложность представляют не только топическая диагностика, но и в первую очередь дифференциальная диагностика АКТГ-зависимых форм ЭГ.…”

“…Второе место по частоте составили карциноиды тимуса -6,9%. В то время как частота НЭО тимуса в целом совпадает с мировыми данными, где новообразования тимуса с эктопической продукцией АКТГ в среднем встречаются в 4,1-8% случаев [15,16] и в единичных работах в 12,5 [14] и 16% случаев [19], частота НЭО бронхолегочной локализации в нашем исследовании самая высокая среди всех представленных в литературе данных.…”

Ectopic Cushing’s Syndrome Secondary to Metastatic Paraganglioma

“…Prior to this case, only a few cases of ectopic ACTH secretion associated with PGLs have been described in the literature [ 27 , 28 ]. As with our patient, in the majority of PGL cases with ectopic ACTH production, patients are female and have metabolic features (hypertension, hyperglycemia, and hypokalemia) [ 27 , 28 ]. However, very few have shown catecholamine hypersecretion [ 27 ].…”

“…However, very few have shown catecholamine hypersecretion [ 27 ]. Most patients with PGL who secrete ACTH have significantly elevated plasma cortisol and ACTH levels [ 27 , 28 ]. However, there is one case described with a normal plasma ACTH level and another with low ACTH levels [ 27 ].…”