Usefulness of prolactin measurement in inferior petrosal sinus sampling with desmopressin for Cushing’s syndrome

Abstract

Background: Bilateral inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary from ectopic adrenocorticotropin (ACTH) excess in patients with ACTH-dependent Cushing’s syndrome. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin (DDAVP) stimulation in localization of the source of ACTH excess.Method: Retrospective review of 20 patients with ACTH-dependent Cushing’s syndrome who underwent IPSS with DDAVP stimulation. Baseline, DDAVP-stimulated, and prolactin-normalized ACTH IPS:P (inferior petrosal sinus to peripheral) ratios were calculated. Cut-off values for each test were obtained from receiver-operating characteristic (ROC) curve analysis.Results: Fifteen patients had Cushing disease (CD), and five were diagnosed with ectopic ACTH syndrome (EAS). For the baseline ACTH IPS:P ratio of ≥2, the diagnostic sensitivity (80%), specificity (100%), positive predictive value (PPV) (100%) and negative predictive value (NPV) (62.5%) were calculated. These values for DDAVP-stimulated IPS:P ACTH ratio ≥ 3, were 86.7%, 100%, 100% and 71.4%, respectively. The corresponding value for the prolactin-normalized ACTH IPS:P ratio ≥ 0.8 were 86.6%, 80%, 92.8% and 66.7%. The cut-off value for the baseline, DDAVP-stimulated and prolactin-normalized ACTH IPS:P ratios were 1.76, 3.9, and 0.33, respectively.Conclusion: Prolactin-normalized ACTH IPS:P ratio measurement showed comparable sensitivity and less specificity than baseline/DDAVP-stimulated IPS/P ACTH ratios. Moreover, when baseline and stimulated IPS/P ACTH tests were discordant, prolactin-normalized ACTH IPS: P ratio correctly localized the source of ACTH excess. The sensitivity of the test increased, applying a prolactin-normalized ACTH IPS: P ratio ≥0.33.