OR42-2 Does Prolactin Measurement Improve Lateralization during IPSS in Patients with Cushing's Disease?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR42-Cushing's Disease & Non-Functioning Hypothalamic-Pituitary Tumours
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 9:30 AM
Room 102 (Moscone Center)
Susmeeta Tewari Sharma*1, Hershel Raff2, Russell R Lonser3, Edward Hudson Oldfield4 and Lynnette Kaye Nieman1
1National Institutes of Health, Bethesda, MD, 2Med College of Wisconsin, Milwaukee, WI, 3National Institutes of Health, 4Univ of Virginia, Charlottesville, VA
Background: Inferior petrosal sinus sampling (IPSS) is the gold standard test to differentiate between Cushing’s disease (CD) and ectopic ACTH syndrome. However, its value in localization of pituitary adenomas in CD remains controversial. Using an inter-sinus ACTH gradient ≥1.4 before or after CRH stimulation, lateralization rates of 50-100% have been reported (1). Prolactin (PRL) measurement during IPSS has been shown to decrease false negative rates (2). Recently, Mulligan et al. (3) reported improved tumor localization with PRL-adjusted ACTH inter-sinus ratios (75% vs. 50%) in 28 CD patients (pts). We further evaluated the utility of PRL in IPSS lateralization in CD.

Methods: Retrospective study of 17 pts with surgically proven CD (2007-2010). Serum PRL levels were measured in stored bilateral petrosal and peripheral IPSS samples, at baseline and at the peak ACTH level after CRH stimulation. PRL adjusted values were calculated by dividing each ACTH value by the concomitant ipsilateral PRL value.

Results: At surgery, 16 of the 17 pts had a single tumor whose epicenter was not midline. One pt with a macroadenoma and unclear location at surgery was excluded. All tumors were positive for ACTH on pathology. MRI of the pituitary, using spoiled gradient ECHO (SPGR) technique, correctly identified the tumor location in 13/16 (81.3%) cases. Using an inter-sinus ACTH gradient ≥1.4, tumor was correctly localized in 12/16 (75%) pts by ratios at baseline and post-CRH, lateralized to the wrong side in 3 and did not lateralize in 1 pt. Using PRL-adjusted ACTH levels, an inter-sinus ratio ≥1.4 correctly identified the tumor location in 11/16 (68.8%) pts. Conflicting results were seen in two pts with reversal of the lateralizing gradient on pre and post-CRH ratios. Lateralization was incorrect at baseline and did not lateralize post-CRH in two pts, and there was no significant inter-sinus gradient in one pt. Based on a basal inferior petrosal sinus to peripheral (IPS/P) PRL ratio (ipsilateral to the peak ACTH IPS/P ratio) of <1.8, unsuccessful catheterization was noted in 3 pts. Of these, lateralization was accurate by both uncorrected and PRL-adjusted ACTH inter-sinus ratios in 2 pts and incorrect by both in 1 pt.

Conclusion: PRL adjustment did not improve the ability of the inter-sinus ACTH gradient to predict tumor location in CD. Value of PRL in lateralization using IPSS remains unclear and needs further study in larger prospective studies.

(1) Newell-Price J, Trainer P, Besser M, Grossman A. Endo Rev 1998; 19:647-72. (2) Sharma ST, Raff  H, Nieman LK. Prolactin as a marker of successful catheterization during IPSS in patients with ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 2011; 96:3687-94 3. (3) Mulligan GB, Faiman C, Gupta M, et al. Prolactin measurement during inferior petrosal sinus sampling improves the localization of pituitary adenomas in Cushing’s disease. Clin Endocrinol 2012;77:268-74.

Nothing to Disclose: STS, HR, RRL, EHO, LKN

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported in part by the intramural program of NICHD, NIH.