Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer.

We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma.

Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. © 2016 S. Karger AG, Basel.