Usefulness of Somatostatin Receptor Scintigraphy in Patients with Occult Ectopic Adrenocorticotropin Syndrome

Abstract

SRIF receptor scintigraphy (SRS) has been proposed for the localization of ectopic ACTH-secreting tumors responsible for Cushing's syndrome. However, in most cases reported, the tumors were also visible using conventional imaging. Therefore, the usefulness of SRS in localizing truly occult ectopic ACTH-secreting tumors remains unknown. We report the results of SRS in 12 patients with ectopic ACTH syndrome (EAS) and in whom the source of ACTH was occult at presentation despite carefully performed conventional imaging. The diagnosis of EAS was made by identification of an ACTH-secreting tumor during follow-up in 5 patients or given a pituitary-toperipheral ACTH ratio of 1.9 or less during petrosal sinus sampling combined with CRH injection and a negative pituitary magnetic resonance imaging (MRI). Whole-body planar SRS, using 111 In-pentetreotide, was performed 19 times in the 12 patients during initial workup and/or follow-up. Axial tomography imaging (single-photon emission-computed tomography) was performed in 7 of these. Conventional imaging was performed within a month of SRS, allowing comparison of the two approaches for the localization of the ACTHsecreting tumors. In addition, the response of plasma cortisol, after a single injection of 200 g octreotide, was studied in 6 patients.Five patients had negative SRS and conventional imaging studies. The source of ACTH secretion remains occult despite 10 -55 months of follow-up in four of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was found at laparotomy in one patient, 14 months after presentation.SRS was positive in 4 of 12 patients. It was false-positive in 1 patient with follicular thyroid adenoma. Nineteen months after presentation, SRS identified liver metastasis that was also visible using MRI in one patient, but the primary tumor remains occult. SRS identified a 10-mm pancreatic tumor that became detectable, using computed tomography (CT) scanning 9 months later, in 1 patient; and 2 mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient, whereas no tumor was detectable within the parenchymal lung. SRS had little influence on therapeutic options in these 2 patients, in whom no final diagnosis could be made. Repetition of SRS during the follow-up of patients with previously negative scintiscans was useless.Conventional imaging was positive in 6 of 12 patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph nodes, conventional imaging studies were interpreted as positive only after the results of SRS. One patient had liver metastasis that was also visible using SRS. Thin-section CT scanning visualized ACTHsecreting bronchial tumors and metastatic mediastinal lymph nodes of 10 -15 mm in diameter in 3 patients after 14 -72 months of followup, whereas SRS was negative.There was no evident relationship between the endocrine status (hyper-or eucortisolism) and the results of SRS. The in vivo response of plasma cortisol to octreotide correlated to the results of SRS in 4 of 6 c...

Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors

“…NETs express somatostatin receptors (SSTs), in particular subtype 2, and can be identified with SSTs scintigraphy with 111 In-pentetreotide octreoscan. In EAS patients, reported sensitivity of the diagnostic octreoscan varies between 25 and 80%, and this broad range may in part be explained by differences in imaging technique protocols (2,7,21,22). Furthermore, we found five patients with negative ACTH immunohistochemistry in our series (lungZ2 and PanNETZ3).…”

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

“…Tabarin and coworkers (24) have questioned the additional utility of SSTR-based functional imaging, arguing that in most positive reported cases, the source of ectopic ACTH was already evident on conventional CT/MRI scans. They have shown the limited utility of SSTR imaging (octreotide-based SPECT imaging) over CECT in a carefully selected cohort of 12 patients with occult EAS on conventional imaging.…”

MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

“…The rationale of high-dose dexamethasone suppression test (HDDST) is that corticotroph pituitary adenomatous cells in Cushing's disease retain partial sensitivity to glucocorticoids, whereas NETs responsible for EAS are fully resistant to exogenous glucorticoid suppression (157). Various thresholds have been proposed in the literature, with a percentage of urinary or serum cortisol suppression varying from 50% to 90% (170,171). However, some authors have shown an almost complete overlap between the response of EAT and corticotropic adenomas and have insisted on the impossibility of finding a discriminating threshold, especially in the case of well-differentiated NETs (172,172).…”