Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing's Syndrome
Authors: Andreea Liliana Serban, Lorenzo Rosso, Paolo Mendogni, Arianna Cremaschi, Rita Indirli, Beatrice Mantovani, Mariagrazia Rumi, Massimo Castellani, Arturo Chiti, Giorgio Alberto Croci, Giovanna Mantovani, Mario Nosotti, Emanuele Ferrante, Maura Arosio
Journal: Front Endocrinol (Lausanne) (2021)
Keywords: cushing’s syndrome, ectopic acth syndrome, hypercortisolism, pulmonary carcinoid, rectal carcinoma
MeSH terms: ACTH Syndrome, Ectopic / diagnostic imaging, Carcinoid Tumor / diagnostic imaging, Cushing Syndrome / diagnostic imaging, Lung Neoplasms / diagnostic imaging, Case Reports, Research Support, Non-U.S. Gov't, ACTH Syndrome, Ectopic / blood, Adrenocorticotropic Hormone / blood, Carcinoid Tumor / blood, Cushing Syndrome / blood, Humans, Lung Neoplasms / blood, Male, Middle Aged, Positron Emission Tomography Computed Tomography, Adrenocorticotropic Hormone

Background:
Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing's syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.
Case presentation:
A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing's syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0-46; basal cortisol levels: 44.2 µg/dl, nv 4.8-19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing's syndrome.
Conclusions:
The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.