Virilizing sclerosing-stromal tumor of the ovary in a young woman with McCune Albright syndrome: clinical, pathological, and immunohistochemical studies.

CONTEXT: McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait skin pigmentations, and gonadotropin-independent sexual precocious puberty, resulting from a somatic postzygotic activating mutation of the GNAS1 gene. SETTING: We report a virilizing sclerosing-stromal tumor of the ovary in a young female with MAS. PATIENT: She presented polyostotic fibrous dysplasia of the left upper and lower limbs and a café-au-lait skin spot in the posterior area of the neck. She had a history of precocious puberty, diagnosed at the age of 6 years and treated with cyproterone acetate until the age of 10 years; then she developed central puberty with severe oligomenorrhea. At the age of 23 years, she was hospitalized for a virilization syndrome including hirsutism, acne, deepening of the voice, amenorrhea, and clitoromegaly. Serum levels of T were dramatically increased (1293 ng/dl; normal range, 10-80). The abdominal computed tomography scan revealed a solid mass located on the left ovary. INTERVENTION: An ovariectomy was performed, and histological examination revealed a sclerosing-stromal tumor with pseudolobular pattern. RESULTS: Immunohistochemical studies revealed that the tumor cells expressed all steroidogenic enzymes involved in androgen synthesis. Molecular analysis revealed that ovarian tumor cells harbored the Arg 201 activating mutation in the GNAS1 gene. After surgery, T levels returned to normal, the patient retrieved a normal gonadal function, and she was able to become pregnant. CONCLUSION: This observation extends the clinical spectrum of ovarian pathology of women with MAS. However, the mechanisms causing this ovarian tumor remain unclear, even if the gsp oncogene has been implicated in the pathogenesis of some gonadal tumors.

Accelerated bone turnover in pregnant women with McCune-Albright syndrome.

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the alpha subunit of G protein, independent of hormonal control, may explain the high local bone turnover.

Bone mineralization in polyostotic fibrous dysplasia: histomorphometric analysis.

Fibrous dysplasia (FD) of bone can be complicated by renal phosphate wasting. The effect of hypophosphatemia on normal and dysplastic bone of FD patients has not been well characterized. In this study, we compared serum phosphorus (sPi) levels to histomorphometric findings in 27 iliac bone samples from 23 children and adolescents (aged 4.2-16.4 years) with polyostotic FD. The samples were separated into two groups, based on the presence (n = 10) or absence (n = 17) of a dysplastic lesion within the specimen. Histomorphometric results were compared with those from 18 age-matched control subjects without metabolic bone disease. In dysplastic lesions, trabeculae were clearly thinner and increased in number. Osteoid indices, osteoblast surface per bone surface, and mineralization lag time were elevated in dysplastic areas, but there was no detectable effect of sPi concentrations on these indices. In nondysplastic bone tissue, low sPi levels were associated with mildly increased osteoid thickness and prolonged mineralization lag time. None of the 13 patients in whom hand X-rays were available at the time of biopsy had radiological signs of rickets. In conclusion, low sPi can cause a mild systemic mineralization defect in FD, but the more severe mineralization defect seen in dysplastic lesions is independent of sPi levels. It is debatable whether the mild systemic mineralization defect warrants treatment with oral phosphorus supplementation if signs of rickets are absent.