McCune–Albright syndrome: surgical and therapeutic challenges in GH-secreting pituitary adenomas

Abstract

McCune-Albright syndrome (MAS) is a postzygotic (non-germline) disorder characterized by polyostotic fibrous dysplasia, cafe-au-lait macules and hypersecretory endocrinopathies. A significant percentage of MAS patients have pituitary adenomas that are either growth hormone (GH) or mixed GH/prolactin (PRL)-producing. Surgical excision may be challenging-or even impossible-due to the associated severe fibrous dysplasia of the skull base. Treatment relies on an interdisciplinary, multi-modal approach from endocrinologists, neurosurgeons and radiation oncologists. We present two cases of women with MAS and GH-secreting pituitary adenomas, encountered in our 30-year experience with pituitary diseases. The first patient successfully underwent transsphenoidal surgical resection for a pituitary microadenoma in 1997 (at age 18) and again in 2009 for recurrent disease, with a significant reduction in IGF-1 level. Immunohistochemistry (IHC) and electron microscopy (EM), performed on both specimens, showed a mammosomatotroph adenoma with GH, PRL, alpha subunit (+) IHC, with increased fibrous bodies developing over the 13-year interval. Focal hyperplasia could be discerned. EM in 1997 showed an admixture of mammosomatotrophs, mature lactotrophs and somatotrophs, with a bimodal population identified in 2009. The second MAS patient had long-standing polyostotic fibrous dysplasia, but was only recently diagnosed with GH excess and a pituitary adenoma, at the age of 29 years. Surgical resection was not advised in this patient because of the massive obstructive skull-base fibrous dysplasia. Medical therapy was initiated with somatostatin analogues, although responses in both patients have been suboptimal to date. We review the literature on GH excess in MAS to highlight its surgical and medical challenges.