Different multiple endocrine neoplasia (MEN) syndromes have been described in humans. These conditions are characterised by different combinations of multiple endocrine tumors based on specific genetic mutations, mainly the MEN1 gene (MEN type 1 syndrome) or in the RET proto-oncogene (MEN type 2). A syndrome encompassing components of both MEN type 1 and type 2, but which is caused by a mutation in the Cdkn1b gene encoding p27, has been described in rats, the so-called MEN X syndrome.
We here present the case of a man with neurofibromatosis, who was diagnosed with a pheochromocytoma, C-cell hyperplasia, and a silent corticotroph pituitary adenoma.
Genetic testing confirmed the presence of the NF-1 mutation (split site mutation at exon 17 (IVS17+2T>C)) without mutations at the RET proto-oncogene (exon 10, 11, 13, 14, 15, 16; MEN type 2 syndrome), VHL-gene (exon 13, Von HippleLindau), or SDHD-gene (at exon 14). Immunohistochemical staining of the pheochromocytoma and the pituitary mass showed reduced expression of the p27 protein in both tissues. Blood DNA of the patient was sequenced, but did not demonstrate the pathogenic mutations in CDKN1B/p27, as it occurs in the MEN X-affected rats.
In conclusion, to our knowledge our case appears to be the first human presenting with features belonging to both MEN type 1 and MEN type 2B. However, we could not confirm a genetic background similar to that reported for the MEN X syndrome in a rat model.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology