Clinical utility of plasma POMC and AgRP measurements in the differential diagnosis of ACTH-dependent Cushing's syndrome

Gabrielle Page-Wilson, Pamela U. Freda, Thomas P. Jacobs, Alexander G. Khandji, Jeffrey N. Bruce, Sandra T. Foo, Kana Meece, Anne White, Sharon L. Wardlaw

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Copyright © 2014 by the Endocrine Society.Context: Distinguishing between pituitary [Cushing's disease (CD)] and ectopic causes [ectopic ACTH syndrome (EAS)] of ACTH-dependent Cushing's syndrome can be challenging. Inferior petrosal sinus sampling (IPSS) best discriminates between CD and occult EAS but is a specialized procedure that is not widely available. Identifying adjunctive diagnostic tests may prove useful. In EAS, abnormal processing of the ACTH precursor proopiomelanocortin (POMC) and the accumulation of POMC-derived peptides might be expected and abnormal levels of other neuropeptides may be detected.Objective: The objective of the study was to evaluate the diagnostic utility of POMC measurements for distinguishing between CD and occult EAS in patients referred for IPSS. Another objective of the study was to evaluate in parallel the diagnostic utility of another neuropeptide, agouti-related protein (AgRP), because we have observed a 10-fold elevation of AgRP in plasma in a patient with EAS from small-cell lung cancer.Design and Participants: Plasma POMC and AgRP were measured in 38 Cushing's syndrome patients presenting for IPSS, with either no pituitary lesion or a microadenoma on magnetic resonance imaging, and in 38 healthy controls.Results: Twenty-seven of 38 patients had CD; 11 of 38 had EAS. The mean POMC was higher in EAS vsCD [54.5 ±13.0 (SEM) vs 17.2 ± 1.5 fmol/mL; P
    Original languageEnglish
    Pages (from-to)E1838-E1845
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume99
    Issue number10
    DOIs
    Publication statusPublished - 1 Oct 2014

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