GROWTH HORMONE-PROLACTIN-THYROTROPIN-SECRETING PITUITARY-ADENOMA IN ATYPICAL MCCUNE-ALBRIGHT SYNDROME WITH FUNCTIONALLY NORMAL G(S-ALPHA) PROTEIN

The McCune-Albright syndrome (MAS) comprises a triad of physical signs : localized bone lesions termed polyostotic fibrous dysplasia, cafe-au -Iait pigmentation of the skin, and autonomous hyperfunction of multip le endocrine systems, including overproduction of GH and T-4. A somati c activating point mutation in the gene for the alpha-subunit of the G -protein (G(s alpha)) in the affected tissue has been claimed to be th e underlying defect. A 29-yr-old patient with MAS, showing polyostotic fibrous dysplasia associated with acromegalic features, underwent end ocrinological studies, including oral glucose tolerance test and pitui tary stimulation test, and magnetic resonance imaging, revealing eleva ted plasma concentrations of GH, PRL, and secondary hyperthyroidism du e to pituitary macroadenoma infiltrating the sphenoid cavity and exten ding to the suprasellar space. Subsequently, reduction of tumor mass b y a transsphenoidal and a subsequent subfrontal operation led to only marginal amelioration of the excessive hormone production. Postsurgery octreotide and bromocriptine therapy induced near-normalization of ho rmone concentrations. Immunohistochemistry of tumor tissue confirmed t he plurihormonal character, but DNA sequence analysis did not detect a ny of the two known activating mutations in the G(s alpha) gene. Furth ermore, biochemical tests revealed normal G(s alpha) function, ruling out other mutations that lead to constitutive G(s alpha) activation. O ur study documents that MAS is a heterogeneous disease. Some, but clea rly not all, patients have oncogenic mutations of the gene coding for G(s alpha). Any gene acting down-stream of G(s) can theoretically be p redicted to result in the same phenotype. In addition, hyperthyroidism of MAS may be secondary to a TSH-producing pituitary macroadenoma.