FP35-3 Serum Metanephrine Levels And Adrenal CT In Pediatric Patients With Multiple Endocrine Neoplasia Type 2B On Vandetanib Therapy

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP35-Neoplasia of Endocrine Tissues
Bench to Bedside
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 122 (Moscone Center)

Poster Board MON-295
Maya Beth Lodish*1, Ninet Sinaii2, Alexander Ling3, Akshintala Srivandana4, Karel Pacak5, Brigitte Widemann4 and Constantine A Stratakis5
1National Institutes of Health (NIH), 2National Institutes of Health, Bethesda, MD, 3NIH, Bethesda, MD, 4National Cancer Institute, 5National Institutes of Health (NIH), Bethesda, MD
Objective: We studied metanephrine (MN) levels and adrenal CT in children and adolescents enrolled in the phase I/II trial of vandetanib (VD) for Multiple Endocrine Neoplasia Type 2B (MEN 2B) and medullary thyroid cancer (MTC),NCT00514046. Pheochromocytomas (PHEO) develop in approximately 50% of patients MEN 2B, usually in their mid-20s (1,2). The majority of PHEOs are intra-adrenal and benign, however the potential for malignancy does exist. Nodular or diffuse hyperplasia of the adrenal medulla occurs as a precursor to the development of PHEO. PHEO in MEN2B have a distinct biochemical phenotype as they consistently produce epinephrine.

Methods: Data from 16 patients with MEN 2B and MTC were analyzed, 9 F, median age 13.3 years (9.1-17.3). 2 patients had unilateral adrenalectomy performed prior to initiating VD. MN levels were followed for a median of 35 mo. (1-51). 15 pts underwent 2 adrenal CTs a mean of 2.2 ± 0.8 years apart (2mm slice thickness, w/IV contrast). These were reviewed by a single radiologist blinded to MN level. Data are reported as median (range), and were compared using paired tests.

Results: Baseline MN level was 55 pg/mL (32-179); 33% were above the ULN of 61. Over the course of the entire study, 87% of patients had at least 1 elevated MN level, with a median peak level of 0.41 x the ULN, (-0.3-2.9). Individual MN levels were more likely to be elevated at any other point over the course of the study compared to baseline (p=0.005). However, in the 10 patients followed for 2-3 y, MN levels remained stable compared to baseline at 59 pg/mL (33-143; p=0.54). None of the adrenal CTs showed enhancing lesions typical of obvious PHEO. 3 patients had possible non-enhancing focal lesions, while 3 patients had adrenal hyperplasia (max. thickness of either the adrenal body or limb of ≥6 mm).

Conclusions: 87% of pediatric MEN2B pts had elevated MN levels at some point over the course of the study; 38% were found to have possible adenoma or hyperplasia on adrenal CT. However, MN levels remained stably elevated; in the absence of controls it is impossible to sort out VD effect vs. natural history of MEN2B. Patients with true PHEO must undergo proper adrenergic blockade to avoid paroxysmal attacks, yet it remains unclear at what point to intervene when the patient has medullary hyperplasia and levels of MN < 3 times ULN. TKIs against RET may be effective in stabilizing medullary hyperplasia, these agents are being further evaluated in this context.

1) O'Riordain DS, O'Brien T, Crotty TB, Gharib H, Grant CS, van Heerden JA 1995 Multiple endocrine neoplasia type 2B: more than an endocrine disorder. Surgery 118:936-942. 2) Leboulleux S, Travagli JP, Caillou B, Laplanche A, Bidart JM, Schlumberger M, Baudin E 2002 Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course. Cancer 94:44-50.

Nothing to Disclose: MBL, NS, AL, AS, KP, BW, CAS

*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 funded by the Intramural Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Cancer Institute. This research was conducted with support from theInvestigator-Sponsored Study Program of AstraZeneca, Wilmington, DE.