Endocrine Abstracts

Introduction: Silent corticotroph tumours (SCT) are a pituitary tumours (PT) subtype of corticotroph lineage that do not clinically express Cushing disease. Inmunohistochemical (IHC) studies reveal no differences between SCT and functioning corticotroph tumours with Cushing Syndrome (FCT). However, the silencing mechanisms of this type of tumours are not fully understood.

Aim: In an important series of SCT, to sequence the POMC gene and quantify the expression of transcription factors of corticotroph lineage (TBX19 (Tpit), NEUROD1) and convertases involved in the processing of POMC (PC1/3) and in the degradation of ACTH (PC2, CPE and PAM).

Material and methods: From our collection of 248 PT we chose 22 SCT, 22 FCT and 26 silent gonadotroph tumours (SGT) (control group). All the adenomas had previously been IHC and molecularly characterized. The molecular identification of SCT was based on an overexpression of POMC, AVPR1b and CRHR1 genes similar to FCT and significantly higher than other subtypes of PT. The molecular study allowed to identify a subtype of SCT IHC negative for ACTH (IHC-ACTH(−)). The gene expression of TBX19, NEUROD1, PC1/3, PC2, CPE and PAM was studied by qRT-PCR with TaqMan probes. Moreover, in 18/22 SCT we performed a Sanger sequencing of the POMC gene.

Results: Preliminary sequencing of POMC in SCT identified some SNPs that are associated with POMC deficiency. Besides, compared with FCT, SCT showed an overall lower expression of PC1/3 (P=0.031), only significant in microadenomas (P=0.05) but not in the FCT macroadenomas. There were no differences in the expression of the other genes studied. Molecularly identified IHC-ACTH (+) SCTs showed a higher PC2 and CPE gene expression than IHC-ACTH (−) ones (P=0.042 and P=0.052, respectively). There were no differences in the expression of the other genes studied. Moreover, and in comparison to FCT, there were no differences in the expression of PC1/3 and PAM between SCT and the control group of GT.

Conclusions: SCT have lower POMC expression and processing than FCT, especially in functioning microadenomas, while ACTH degradation is similar in both subtypes. Indeed, the expression of the genes involved in the degradation of ACTH seems to be related to the amount of this hormone in the tumour. Moreover, SCT share some similarity with SGT in the processing of POMC and in the degradation of ACTH, suggesting the possible existence of silent corticogonadotroph tumours.