Expression of Somatostatin receptors in normal adrenal and in Primary Pigmented Nodular Adrenocortical Disease (PPNAD). A possible new use for somatostatin analogues

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 1-36-Adrenal Incidentaloma & Carcinoma
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-8
Paraskevi Xekouki*1, Zakariae Bram2, Estelle Louiset2, Dimitrios Avgeropoulos1, Maria V Nesterova1, Ninet Sinaii3, Herve Lefebvre4 and Constantine A Stratakis1
1National Institutes of Health (NIH), Bethesda, MD, 2Institut de Recherche et d'Innovation Biomédicale, Université de Rouen, France, 3National Institutes of Health, Bethesda, MD, 4Inserm U982, Institut de Recherche et d'Innovation Biomédicale, Université de Rouen, France and Service d'Endocrinologie, Diabète et Maladies Métaboliques, Institut de Rech, Rouen, France
Background: Somatostatin receptors (SSTRs) are expressed in many normal human tissues and in several tumors such as adrenal cortical adenomas and pheochromocytomas (PHEOs). Somatostatin analogues (SSA) have been used successfully for the treatment of a 49-year-old woman with nodular adrenal hyperplasia and food dependent Cushing syndrome (1). Aim of the study: In the present study we examined the SSTRs expression and the effect of short-acting octreotide on cortisol levels in patients with PPNAD in vitro and in vivo. Subjects and methods: Ten subjects diagnosed with PPNAD with or without a PRKAR1A mutation were tested on two separate days, with random assignment to treatment with octreotide and placebo.  Serial cortisol measurements were taken every 30 minutes for 12 hours in total. In the in vitro study tissue specimens from patients with PPNAD, isolated micronodular adrenocortical disease (iMAD), or macronodular adrenocortical disease (MAD) with or without mutations in genes related to these conditions and the immortalized PPNAD cell line (CAR47) were used for the expression and localization of the SSTRs although it has lost its steroid hormone-producing capacity (2). Results: No difference was observed in pre-treatment cortisol levels between somatostatin and placebo groups. Pre- versus post-treatment cortisol values were significantly higher (p<0.0001 for both groups), with overall lower levels post-treatment. Expression of SSTRs (particularly of SSTR1-3) was increased in PPNAD tissues with a PRKAR1A mutation compared to normal adrenal and to tissues from other adrenal diseases. Using the CAR47 cell line we showed that 24h incubation with somatostatin enhanced the expression mainly of SSTR2. Conclusions: We showed that SSTR expression in PPNAD tissues was significantly higher compared to normal adrenal and to tissues from other adrenal diseases. The reduction (although not significant) seen in some patients following octreotide administration, indicates that SSAs may be considered as treatment for PPNAD patients when adrenalectomy is not an option or in case of disease recurrence; additional studies with higher doses are needed to determine if this may be an option for all patients with PPNAD.

(1) Reznik Y et al., N Engl J Med. 1992; 327:981. (2) Nesterova M et al., J Clin Endocrinol Metab. 2008;93:565

Nothing to Disclose: PX, ZB, EL, DA, MVN, NS, HL, CAS

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