Management of Occult Adrenocorticotropin-Secreting Bronchial Carcinoids: Limits of Endocrine Testing and Imaging Techniques

Abstract

The differential diagnosis and the identification of the source of ACTH in occult ectopic Cushing's syndrome due to a bronchial carcinoid still represents a challenge for the endocrinologist. We report our experience in six patients with occult bronchial carcinoid in whom extensive hormonal, imaging, and scintigraphic evaluation was performed. All patients presented with hypercortisolism associated with high plasma ACTH values. The CRH test and high dose dexamethasone suppression test suggested an ectopic source of ACTH in three of six patients. During bilateral inferior petrosal sinus sampling, none of the patients showed a central to peripheral ACTH gradient. At the time of diagnosis, none of the patients had radiological evidence of the ectopic source of ACTH, whereas pentetreotide scintigraphy identified the lesion in two of four patients. Finally, a chest computed tomography scan revealed the presence of a bronchial lesion in all patients, and pentetreotide scintigraphy identified four of six lesions. In all patients a bronchial carcinoid was found and removed. In one patient with scintigraphic evidence of residual disease after two operations, radioguided surgery, using a hand-held gamma probe after iv administration of radiolabeled pentetreotide, was performed; this allowed detection and removal of residual multiple mediastinal lymph node metastases. In conclusion, our data show that there is not a single endocrine test or imaging procedure accurate enough to diagnose and localize occult ectopic ACTH-secreting bronchial carcinoids. Radioguided surgery appears to be promising in the presence of multiple tumor foci and previous incomplete removal of the tumor.

Paraneoplastic syndromes secondary to neuroendocrine tumours

“…It has been suggested that no single endocrine test and/or imaging procedure are accurate enough to diagnose and localise ectopic ACTH/CRH-producing bronchial carcinoids, particularly as false positive IPSS results may occasionally be obtained, albeit very rarely (Young et al 1998, de Herder & Lamberts 1999, Baudin et al 2001, Loli et al 2003. In such cases, scintigraphy with 111 In-octreotide, particularly after correction of hypercortisolaemia, and PET using several novel tracers can be used to reveal confounding cases eluding localisation (de Herder et al 1994, Tsagarakis et al 2003, Kaltsas et al 2004b, Markou et al 2005.…”

Pitfalls in the diagnosis of Cushing's syndrome

“…It may be particularly useful in the detection of lesions not visualized by CT or MRI, particularly occult bronchial carcinoids (74). However, in most studies, all tumors disclosed by SRS were apparent on conventional imaging (2,4,44).…”

“…However, in most studies, all tumors disclosed by SRS were apparent on conventional imaging (2,4,44). An analysis of 7 studies examining the usefulness of SRS in EAS demonstrated diagnostic sensitivity ranging from 33% to 80% for tumor localization (44,71,(74)(75)(76)(77)(78)(79).…”

“…SRS should always be correlated with conventional imaging studies because of false-positive results that have been reported in certain conditions, such as granulomatous lesions, autoimmune lesions, inflammation, follicular thyroid adenomas, radiation fibrosis, lymphomas, and accessory spleen (43,74,78). Moreover, SRS has limited sensitivity in the detection of tumors < 1 cm (74).…”

“…Moreover, SRS has limited sensitivity in the detection of tumors < 1 cm (74). There have been a few reports of negative SRS becoming positive, and repeat SRS should be considered during long-term follow-up in persistent occult disease (76).…”