title: Mifepristone effects on tumor somatostatin receptor expression in two patients with Cushing's syndrome due to ectopic adrenocorticotropin secretion.
abstract: BACKGROUND
  Two patients presented with Cushing's syndrome due to ectopic ACTH secretion. Initial localization studies included computed tomography, magnetic resonance imaging, and octreoscans ((111)In-pentreotide scintigraphy), which were negative in both patients. They were treated with the glucocorticoid receptor antagonist mifepristone, with improvement in their clinical symptoms. Follow-up octreoscans after, respectively, 6 and 12 months showed the unequivocal presence of a bronchial carcinoid in both patients.
  
  
  OBJECTIVE
  The objective of the study was to correlate in vivo and in vitro findings in patients with ectopic ACTH-producing syndrome.
  
  
  METHODS
  We determined the expression of somatostatin and dopamine receptors by immunohistochemistry (patients 1 and 2), quantitative PCR, and in vitro culturing of tumor cells (patient 1 only). IN VITRO RESULTS: Both tumors were strongly positive for somatostatin receptor type 2 (sst(2)) on immunohistochemistry, whereas one of the tumors (patient 1) was also dopamine receptor subtype 2 (D(2)) positive on both immunohistochemistry and quantitative PCR. Octreotide (a sst(2) preferring analog) and cabergoline (D(2) agonist) both decreased the ACTH levels in the cultured tumor cells of patient 1.
  
  
  CONCLUSIONS
  We describe two patients with ACTH-producing bronchial carcinoids, in whom a direct down-regulatory effect of glucocorticoid levels on tumoral sst(2) receptor expression is suggested by a remarkable change in octreoscan status after successful mifepristone therapy. Further studies will have to demonstrate whether glucocorticoid lowering or antagonizing therapy may be used to improve the diagnostic accuracy of somatostatin receptor scintigraphy in patients with ectopic ACTH production of unknown primary origin.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: de Bruin
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
authors.forename: P M
authors.initials: PM
authors.lastname: van Koetsveld
authors.forename: A M
authors.initials: AM
authors.lastname: Waaijers
authors.forename: D M
authors.initials: DM
authors.lastname: Sprij-Mooij
authors.forename: M
authors.initials: M
authors.lastname: van Essen
authors.forename: S W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D002276:Carcinoid Tumor / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003480:Cushing Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology* / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D017481:Receptors, Somatostatin; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone
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