Abstract 532
Poster Session I, Saturday, 5/1 (poster 315)
McCune-Albright Syndrome (MAS) is a heterogeneous disorder that causes a wide variety of abnormalities in endocrine and non-endocrine tissues. Classically described as a triad of polyostotic fibrous dysplasia, cafe au lait spots, and sexual precocity MAS can cause autonomous production of multiple endocrine hormones with variable degree of skin and bone manifestations in children and rarely in infants. Activating mutations of Arg201 in Gsα, the G protein that stimulates cAMP production, cause MAS in children by stimulating downstream signal transduction pathways in affected tissues autonomously. The Gsα gene is involved in the signal transduction of many hormones including several not previously described as affected in MAS, such as CRH. We describe a female infant born at 36 weeks gestation with respiratory distress and multiple congenital abnormalities (dysplastic bones, a small thorax, and dysmorphic facies) who developed hypersecretion of multiple endocrine hormones including Cushing's Disease over the first few months of life. Adrenal androgen and cortisol levels were markedly elevated. Plasma ACTH was also elevated and only partially suppressed by dexamethasone, suggesting that the patient had pituitary Cushing's disease. The infant developed primary hyperthyroidism with suppressed TSH. The infant also developed signs excess estrogen effect on vaginal mucosa. The infant developed severe hypertension, progressive respiratory insufficiency, progressive neurological impairment, failure to thrive, and signs of glucocorticoid excess including hypertrophic cardiomyopathy. By 3 1/2 months of age that infant became respirator-dependent, could not feed orally, and support was withdrawn. At autopsy the infant had abnormalities in multiple tissues. Bone architecture was disorganized with generalized osteopenia. Brain mass was decreased with a delay in CNS myelination. Immunocytochemistry of the pituitary showed nodular hyperplasia in the pars intermedia with a marked increase in ACTH-containing anterior pituitary cells, consistent with Cushing's disease. PCR of genomic DNA with restriction enzyme analysis of the Gsα gene showed a C→T mutation in liver and adrenal tissue in the Gsα gene (Arg→ Cys), typical of MAS common mutation of MAS. Conclusions: 1) MAS can cause severe multifaceted manifestations in neonates. 2) Cushing's Disease can occur in MAS. 3) Atypical bony abnormalities, rather than the more usual polyostotic fibrous dysplasia, may occur in neonates with MAS.
