A case of ectopic ACTH syndrome due to DDAVP-sensitive but V1b receptor-negative bronchial typical carcinoid with lymphatic metastasis and plasma ProGRP elevation

Abstract

Ectopic ACTH syndrome (EAS) is a potentially fatal endocrine disease that results from a variety of neuroendocrine tumors (NETs), such as small cell lung cancer (SCLC) and bronchial typical carcinoid. Typical carcinoid is usually slow growing, not associated with plasma progastrin releasing peptide (ProGRP) elevation. Here, we report a 47-year-old female smoker with progressive typical carcinoid and plasma ProGRP elevation. Several types of Cushingoid features were found on physical examination. In addition, laboratory examination showed elevated plasma ACTH and serum cortisol levels. These findings indicated ACTH-dependent Cushing's syndrome. Moreover, the serum cortisol level was not suppressed by overnight high-dose dexamethasone treatment, suggesting the presence of an extra-pituitary tumor. Contrast-enhanced brain MRI revealed no pituitary adenoma, which also supported the idea that EAS occurred in the present case. Strikingly, chest computed tomographic (CT) scan showed a single 18-mm peripheral nodule in the right middle lobe of the lung. Tumor marker analysis revealed an elevation in plasma ProGRP. These data suggested a possibility that SCLC secreted ACTH and caused EAS in this patient. Of note, the plasma ACTH level was increased (1.7 fold) in l-desamino-8-D-arginine vasopressin (DDAVP) test, also suggesting the specific clinical feature in this case. After additional imaging examinations, we performed surgical resection with the suspicion of limited SCLC. As a result, pathological examination revealed a vasopressin receptor Ib (V1b) receptor-negative bronchial typical carcinoid with ACTH production and mediastinal lymphatic metastasis. In summary, we present a case of EAS caused by progressive bronchial typical carcinoid with plasma ProGRP elevation. We propose a novel subtype of lung typical carcinoid.

Neuroendocrine syndrome in bronchial carcinoid tumors

“…A case of a bronchial carcinoid associated with Cushing syndrome and elevated Pro-GRP in relation with V1b (negative vasopressin receptor) was reported. With this data the authors proposed a new subtype of typical bronchial carcinoid (7). The American Clinical Oncological Society proposed the association of all neuroendocrine tumors, benign and malignant, under a new concept-NET (neuroendocrine tumor).…”

“…It can present with bronchoconstriction, flush, hemodynamic instability, tachycardia and accelerated digestive transit (6). Cushing syndrome is the second syndrome caused by carcinoid tumors and is determined by the ectopic production of ACTH (adrenocorticotropic hormone) (7). Another syndrome associated with bronchial carcinoid tumors is that of an inadequate secretion of AVP (arginine vasopressin) which may lead to sodium depletion and water retention.…”

Pro-Gastrin-Releasing Peptide as a Biomarker in Lung Neuroendocrine Neoplasm

“…ProGRP has been studied extensively in SCLC [ 12 , 13 ]. However, very little data are available on ProGRP levels in the blood serum of patients with LNENs [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”