Dopamine receptor expression and function in corticotroph ectopic tumors

Rosario Pivonello, Diego Ferone, Wouter W. De Herder, Antongiulio Faggiano, Lisa Bodei, Ronald R. De Krijger, Gaetano Lombardi, Annamaria Colao, Steven W J Lamberts, Leo J. Hofland

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Dopamine receptor (DR) expression and dopamine agonist (DA) effectiveness have never been demonstrated in neuroendocrine tumors associated with ectopic ACTH syndrome (EAS). Aim: The aim of the current study was to evaluate DR and particularly D2 subtype expression in neuroendocrine tumors associated with EAS and to evaluate the in vivo effectiveness of the DA cabergoline in the treatment of EAS. Patients and Methods: Six ACTH-secreting neuroendocrine tumors, including four lung, one pancreatic, and one thymic carcinoid, were used for the evaluation of D2 expression by immunohistochemistry. DR subtypes and D2 isoforms and number were evaluated by RT-PCR in three cases of persistent EAS after surgery. These patients were treated with cabergoline at the dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor size were monitored during the treatment period. Results: At immunohistochemistry, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was confirmed in all three cases but at variable numbers, whereas D4 was expressed in two cases. D2long was expressed in all three cases, together with D2short in one case. A normalization of urinary cortisol levels was found in two patients (66.7%) after 3 months of treatment. However, treatment escape was demonstrated in one of these patients afterward. Conclusion: The results of this study demonstrated that DR are expressed in neuroendocrine tumors associated with EAS and that cabergoline treatment could be effective in controlling cortisol excess in a subgroup of patients with EAS. Further studies on a larger number of patients are mandatory to confirm the usefulness of DA in EAS.

Original languageEnglish
Pages (from-to)65-69
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number1
DOIs
Publication statusPublished - Jan 2007

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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