CLONALITY OF GH SECRETING PITUITARY ADENOMAS IN RELATION TO RESPONSE TO SOMATOSTATIN ANALOGUES. CASES REPORT

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 167-198-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-194
Ionela Baciu1, Serban Radian1, Andra Caragheorgheopol2, Anda Dumitrascu2, Monica Gheorghiu1, Vasilie Ciubotaru3 and Mihail Coculescu*1
1C Davila University of Medicine and Pharmacy, Bucharest, Romania, 2Constantin I Parhon National Institute of Endocrinology, Bucharest, Romania, 3Bagdasar-Arseni Emergency Hospital, Bucharest, Romania
Introduction About 25% of acromegalic (ACM) patients treated with somatostatin analogues (SSAs) do not achieve optimal control of disease. To date no study related to the relationship between clonality and therapeutic response of ACM was performed.

Aim. To investigate the relation between tumor pattern of clonal development and the response of ACM to surgery followed by SSAs.

Patients and methods. Eight sporadic ACM female patients were evaluated for tumor clonality using HUMARA method (human androgen receptor-AR gene analysis). Blood DNA was used to asses heterozigosity for AR locus and as a positive control tissue. Tumor DNA from a male ACM patient was used as a hemizygot control. DNA was extracted from blood and RNAlater-conserved tissue using Promega Wizard® DNA purification kit, was incubated with HpaII or water (control) and fluorescent-labeled PCR products of AR exon 1 (including CAG repeat and 2 HpaII sites) were sized with the CEQ8000 Analyzer (Beckman). A clonality ratio<0.4 indicated monoclonality. Due to the limited number of cases, statistic validation was not applicable.

Results. 4 tumors were monoclonal (M) and 4 polyclonal (P). The size of M adenomas was bigger then that of P adenomas (20.32mm versus 12.62mm). The first effect was the complete removal of the tumor by surgery in 2 P cases. Considering the GH production, evaluated by seric GH and IGF1 levels, it was higher in M compared to P cases: 37.8ng/mL versus 20,05ng/mL for GH and 4.7X upper limit of normal versus 4.1X for IGF1. All cases but one were responsive to SSAs. The nonresponsive case was policlonal and had a GH value that started at 45.9ng/mL (prior to surgery), reached 22.5 after surgery and was not modified by octreotid 30mg/28days (26ng-mL), with a small decrease after one year of Pasireotid 60mg/28days (18.5ng/mL). The M cases show a decrease of GH values under treatment: 37.8ng/mL prior to surgery, 4.68 after surgery and 1.36 after SSAs. The P cases started at 20.05ng/mL and decreased to 6.18 after surgery and 13.31 ng/mL under octreotid. The P adenoma responsive to octreotid was polihormonal (imunohistochemistry: GH++ and TSH+). The polihormonal expression did not produce resistence to SSAs therapy.

Conclusion. Polyclonality does not constantly produce different clinical and secretory characteristics in ACM, although they are smaller in size when compared to monoclonal adenomas. However only between P adenomas we found a non-responder to SSAs and another one polihormonal.

Nothing to Disclose: IB, SR, AC, AD, MG, VC, MC

*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 by CNCSIS TE 227/2010 and PNCDI2 41-014/2007 grants from the Romanian Ministry of Education. We thank C. Badiu, MD and R. Trifanescu,MD for referring patients.