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 multiple endocrine systems, including overproduction of GH and T-4. A somatic 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 the underlying defect. A 29-yr-old patient with MAS, showing polyostotic fibrous dysplasia associated with acromegalic features, underwent endocrinological studies, including oral glucose tolerance test and pituitary stimulation test, and magnetic resonance imaging, revealing elevated plasma concentrations of GH, PRL, and secondary hyperthyroidism due to pituitary macroadenoma infiltrating the sphenoid cavity and extending to the suprasellar space. Subsequently, reduction of tumor mass by 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 hormone concentrations. Immunohistochemistry of tumor tissue confirmed the plurihormonal character, but DNA sequence analysis did not detect any of the two known activating mutations in the G(s alpha) gene. Furthermore, biochemical tests revealed normal G(s alpha) function, ruling out other mutations that lead to constitutive G(s alpha) activation. Our study documents that MAS is a heterogeneous disease. Some, but clearly 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 predicted to result in the same phenotype. In addition, hyperthyroidism of MAS may be secondary to a TSH-producing pituitary macroadenoma.