McCune-Albright Syndrome in Clinical Practice

Abstract

McCune-Albright syndrome (MAS) is a rare disease combining polyostotic fibrous dysplasia (FD), pigmented café-au-lait macules, and endocrine disorders, the most characteristic being precocious puberty (PP). It is related to a somatic point mutation of the gene encoding guanine nucleotide-binding α-subunit gene (GNAS) that leads to constitutive adenylyl cyclase activation and increased cellular cAMP production in the endocrine organs known to be involved in the syndrome (the ovary, testicle, bone, pituitary, and thyroid and adrenal glands). The mutations are postzygotic and have a mosaic distribution, which explains the large phenotypic variability of the syndrome. The clinical management of endocrine conditions in this disease is illustrated by two clinical cases. Precocious puberty is related to gonadotropin-independent autonomous ovarian activation. Gonadal function and fertility are often abnormal in women with MAS when they become adults. Precocious puberty is much rarer in boys. Nevertheless, macroorchidism with benign lesions on ultrasound (US) is much more frequent and generally remains stable in adulthood. Acromegaly may be characterized by gigantism if beginning before puberty or may appear in adulthood. Pituitary adenomas are often difficult to treat surgically because of skull base dysplasia. Somatostatin analogs are only partially effective in most cases; fortunately, the GH receptor antagonist pegvisomant may be more effective at normalizing IGF-I levels. Hyperthyroidism, generally due to multinodular toxic goiter, can be successfully treated by surgery or radioiodine administration. Recent data suggest that the cancer incidence in adulthood (bone, breast, thyroid, etc.) is increased in these patients.