McCune-Albright syndrome in adulthood

The McCune-Albright syndrome is characterized by cafe-au-lait spots, precocious puberty and fibrous dysplasia. It is due to mutations in the gene encoding the Gs protein alpha subunit coupling 7-transmembrane-domain receptors to adenylate cyclase, leading to constitutive adenylate cyclase activation and cAMP overproduction. Endocrinologists, rheumatologists and gynecologists are confronted with new issues when these children reach adulthood. Dysplastic bone lesions seem to stabilize after puberty, but their disabling consequences (pain, fractures, etc.) may continue into adulthood. Gonadal function and fertility are often abnormal in women in whom puberty was precocious, owing to the persistence of a variable degree of ovarian autonomy that hinders adequate follicular development and ovulation. Acromegaly, when present, is 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 in normalizing IGF-I levels. Hyperthyroidism, generally due to multinodular toxic goiter, can be successfully treated by surgery or radioiodine administration. Recent data suggest that cancer incidence in adulthood (bone, breast, thyroid...) is increased in these patients.