ESPE Abstracts

Background: Beckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of embryonic tumors during early childhood. About 80% of patients with BWS show a molecular defect in the 11p15 imprinted region. Loss of methylation at the imprinting control region 2 (ICR2) is the most frequent defect which leads to a loss of expression of the CDKN1C gene, increasing cell proliferation. These epigenetic defects occur mostly as a mosaic event.

Objective and hypotheses: We describe the first case of Cushing disease secondary to an ACTH microadenoma of the pituitary in a patient with BWS.

Method: Methylation status of the 11p15 region was assessed with the ASMM-MQ6PCR.

Results: A 19-year-old female patient has been referred in an endocrinology reference centre for excessive weight gain, hirsutism and secondary amenorrhea. Furthermore, she presented hemihyperplasia, and macroglossia was noticed by the parents during the first years of age. Blood test showed persistant elevated levels of cortisol through the 24 h, with elevated free urinary cortisol, and inappropriate ACTH levels. Dynamic tests (dexamethasone suppression tests and stimulating tests) confirmed the ACTH dependant hypercortisolism. MRI showed a microadenoma of the pituitary. After surgery, the adenoma was positive for ACTH staining. Methylation analysis of the 11p15 region found a loss of methylation at ICR2 in a mosaic state in the leucocytes (methylation index (MI): 17%, normal values 48–53), and a total loss of methylation in the adenoma (MI: 1%).

Conclusion: We report the first case of pituitary adenoma in a patient with BWS diagnosed at the adult age. We showed that the molecular defect was present in a higher proportion in the pituitary gland, which may have led to the adenoma. This report highlights the variable expressivity of BWS, and such a diagnosis should be evoked in case of a tumoural process with hemihyperplasia.