Introduction: McCuneAlbright syndrome (MAS) is a rare disease resulting from a somatic activating mutation of GNAS1 encoding the Gs-alfa subunit of the G-protein coupled membrane receptor responsible for multiple hormonal signaling cascades leading to the classical trias: polyostotic fibrous dysplasia, café-au-lait hyperpigmentation and GnRh independent precocious puberty. Early manifestation is accompanied with multiple organ involvement and may lead to ACTH-independent hypercortisolism, hyperthyroidism, cardiac alterations, hepatopathy and GH-Excess in addition to the classical trias.
Case report: We report a case of neonatal MAS in a girl with apparent manifestation at the age of 6 weeks with ACTH-independent Cushing syndrome, HOCM, hyperthyroidism, hepatopathy, bilateral nephrocalcinosis and autonomous ovarian cysts besides the café-au-lait hyperpigmentation. We describe the clinical course with initial metyrapone therapy to control hypercortisolism. Side effects as hypertension and hyperandrogenemia were observed. The girl developed hypercalcemia at the age of 3 month with the need of bisphosphonate therapy. The course was complicated by appearance of acute abdomen at the age of 4 months, caused by a ruptured large juvenile ovarian granulosa cell tumor. Tumor cells contained highly expressed androgen receptors. It can be assumed that high androgen levels as side effect of metyrapone therapy have caused rapid growth of ovarian tumor cells. Bilateral adrenalectomy was performed to stop hyperandrogenemia at the age of 5 month in head of the tumor. Activating mutation in the GNAS-Gen (c.602G>A; p.R201H) was found in the ovarian tumor cells and in the adrenal glands.
Conclusion: Early manifestation of MAS is accompanied by multiple organ involvement. Juvenile granulosa cell tumor (JGCT) is a rare tumor. Activating GNAS mutation can be found in JGCT cells. JGCT has not been described in MAS. Metyrapone is effective to control hypercortisolism but leads to high androgen levels. It has to be taken into account that high androgen levels under metyrapone can cause rapid growth of existing tumor cells as observed in this case.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology