To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.
T Suda, F Tozawa, I Dobashi, N Horiba, N Ohmori, M Yamakado, M Yamada, H Demura
Title and authors | Publication | Year |
---|---|---|
Cushing syndrome.
Nieman LK, Castinetti F, Newell-Price J, Valassi E, Drouin J, Takahashi Y, Lacroix A |
Nature reviews. Disease primers | 2025 |
Longitudinal Evaluation of Reproductive Endocrine Function in Men With ACTH-Dependent Cushing Syndrome
Shekhar S, McGlotten RN, Cutler GB Jr, Crowley MJ, Pieper CF, Nieman LK, Hall JE |
The Journal of Clinical Endocrinology and Metabolism | 2024 |
Molecular Derangements and the Diagnosis of ACTH-Dependent Cushing’s Syndrome
Nieman LK |
Endocrine reviews | 2021 |
The Mechanisms Underlying Autonomous Adrenocorticotropic Hormone Secretion in Cushing’s Disease
H Fukuoka, H Shichi, M Yamamoto, Y Takahashi |
International journal of molecular sciences | 2020 |
High accuracy of bilateral and simultaneous petrosal sinus sampling with desmopressin for the differential diagnosis of pediatric ACTH-dependent Cushing’s syndrome
LB Cavalcante, TC Freitas, NR Musolino, VA Cescato, GO Silva, MC Fragoso, P Puglia, MD Bronstein, MC Machado |
Pituitary | 2020 |
Ectopic cushing’s syndrome due to corticotropin releasing hormone
M Nakhjavani, A Amirbaigloo, S Rabizadeh, F Rotondo, K Kovacs, AA Ghazi |
Pituitary | 2019 |
Two types of ectopic Cushing syndrome or a continuum? Review
MA Castro, MM Azpiroz |
Pituitary | 2018 |
An activating mutation in the CRHR1 gene is rarely associated with pituitary-dependent hyperadrenocorticism in poodles
V De-Marco, LR Carvalho, MF Guzzo, PS Oliveira, LG Gomes, BB Mendonca |
Clinics | 2017 |
Adrenal Disorders
AC Levine |
Adrenal Disorders | 2017 |
Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas
MF Cassarino, A Sesta, L Pagliardini, M Losa, G Lasio, F Cavagnini, FP Giraldi |
Endocrine | 2016 |
Endocrinology: Adult and Pediatric
M Gurnell, TJ Visser, P Beck-Peccoz, VK Chatterjee |
Endocrinology: Adult and Pediatric | 2016 |
Endocrinology
C Napier, SH Pearce |
Endocrinology | 2016 |
Neuropeptide Y Attenuates Stress-Induced Bone Loss Through Suppression of Noradrenaline Circuits: NPY PROTECTS FROM STRESS-INDUCED BONE LOSS
PA Baldock, S Lin, L Zhang, T Karl, Y Shi, F Driessler, A Zengin, B Hörmer, NJ Lee, IP Wong, EJ Lin, RF Enriquez, B Stehrer, MJ During, E Yulyaningsih, S Zolotukhin, ST Ruohonen, E Savontaus, A Sainsbury, H Herzog |
Journal of Bone and Mineral Research | 2014 |
Evaluation of the diagnostic criteria for Cushing^|^rsquo;s disease in Japan [Review]
K Kageyama, Y Oki, S Sakihara, T Nigawara, K Terui, T Suda |
Endocrine Journal | 2013 |
Locomotor sensitization to EtOH: contribution of β-Endorphin
S Dempsey, JE Grisel |
Frontiers in molecular neuroscience | 2012 |
THE GLUCOCORTICOID RECEPTOR AND ITS EXPRESSION IN THE ANTERIOR PITUITARY AND THE ADRENAL CORTEX: A SOURCE OF VARIATION IN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION; IMPLICATIONS FOR PITUITARY AND ADRENAL TUMORS
G Briassoulis, S Damjanovic, P Xekouki, H Lefebvre, CA Stratakis |
Endocrine Practice | 2011 |
The corticotropin releasing factor system in cancer: expression and pathophysiological implications
A Kaprara, K Pazaitou-Panayiotou, A Kortsaris, E Chatzaki |
Cellular and Molecular Life Sciences | 2010 |
Yen & Jaffe's Reproductive Endocrinology
RA Lobo |
Yen & Jaffe's Reproductive Endocrinology | 2009 |
Evaluation of Diagnostic Tests for ACTH-Dependent Cushing’s Syndrome
T SUDA, K KAGEYAMA, T NIGAWARA, S SAKIHARA |
Endocrine Journal | 2009 |
Evaluation of proopiomelanocortin mRNA in the peripheral blood from patients with Cushing’s syndrome of different origin
S Bondioni, G Mantovani, N Polentarutti, B Ambrosi, P Loli, E Peverelli, AG Lania, P Beck-Peccoz, A Spada |
Journal of Endocrinological Investigation | 2007 |
The Nelson's syndrome... revisited
G Assié, H Bahurel, J Bertherat, M Kujas, P Legmann, X Bertagna |
Pituitary | 2004 |
Physiological roles of urocortins, human homologues of fish urotensin I, and their receptors
T Suda, K Kageyama, S Sakihara, T Nigawara |
Peptides | 2004 |
Endocrine paraneoplastic syndromes in lung cancer
PJ Mazzone, AC Arroliga |
Current Opinion in Pulmonary Medicine | 2003 |
The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome
G Reimondo, P Paccotti, M Minetto, A Termine, G Stura, M Bergui, A Angeli, M Terzolo |
Clinical Endocrinology | 2003 |
The Role of Hormones, Growth Factors and Their Receptors in Pituitary Tumorigenesis
S Ezzat |
Brain Pathology | 2001 |
Ectopic ACTH syndrome: Molecular bases and clinical heterogeneity
M Terzolo, G Reimondo, A Alì, S Bovio, F Daffara, P Paccotti, A Angeli |
Annals of Oncology | 2001 |
Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress
A Slominski, J Wortsman, T Luger, R Paus, S Solomon |
Physiological reviews | 2000 |
Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells
T Suzuki, M Yamaya, K Sekizawa, N Yamada, K Nakayama, S Ishizuka, M Kamanaka, T Morimoto, Y Numazaki, H Sasaki |
American journal of physiology. Lung cellular and molecular physiology | 2000 |
The Cytogenesis and Pathogenesis of Pituitary Adenomas*
SL Asa, S Ezzat |
Endocrine reviews | 1998 |
The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome
Y Keyzer, F Lenne, C Auzan, S Jégou, P René, H Vaudry, JM Kuhn, JP Luton, E Clauser, X Bertagna |
Journal of Clinical Investigation | 1996 |
Cushing's Syndrome
DN Orth |
New England Journal of Medicine | 1995 |