Ectopic ACTH syndrome: our experience with 25 cases

Abstract

Objective: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111 In-pentetreotide scintigraphy were revised. Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH-and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases.111 In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.European Journal of Endocrinology 155 725-733

Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study

“…The favorable survival rate of BC compared with other ACTH-secreting tumors had already been observed in other studies (6,7,19). Conversely, survival rate of occult tumors in our series was poorer than that of BC and similar to that of pNET, in contrast to the results reported by Ilias et al (6).…”

Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis

“…high plasma ACTH and serum cortisol levels and a lack of response to CRH, even though the rare EAS patients with mild hypercortisolism can theoretically escape detection from the parameter combinations (12,(23)(24)(25)(26). The characteristics of the hCRH response and the above correlations, reflecting a preserved physiological negative feedback mechanism in CT and PC subjects and its loss in CS patients, have also partially been described.…”

Evaluation of Diagnostic Tests for ACTH-Dependent Cushing’s Syndrome

“…Salgano et al reported that a high dose of dexamethasone caused a high false-positive rate in lung carcinoid tumors [2]. These results suggest that a high-dose dexamethasone test is also useful for the diagnosis of Cushing's disease, although we have to pay attention to the results produced in macroadenomas with Cushing's disease and in cases of bronchial carcinoids with EAS [14].…”

“…ACTH release would be caused by an abnormal increase in vasopressin type 1b receptors in response to a vasopressin type 2 receptor agonist, DDAVP, on pituitary corticotroph adenoma cells [6], and has been used for the differential diagnosis of ACTH-dependent Cushing's syndrome [7]. Nevertheless, the data in Cushing's disease has been known to overlap with some cases of EAS [2]. In discussing the present diagnostic criteria, we refer to our extensive data.…”

“…Cushing's disease is primarily caused by a pituitary ACTH-secreting tumor, while ectopic ACTH syndrome (EAS) is considered to be a result of extrapituitary ACTH-secreting tumors, such as bronchial carcinoid, thymic carcinoid, pheochromocytoma, and so on [2]. The diagnosis and differential diagnosis of ACTH-dependent Cushing's syndrome are challenging problems in clinical endocrinology.…”