Endocrine Abstracts

McCune-Albright syndrome (MAS) is a rare mosaic disorder caused by a postzygotic activating mutation in the GNAS gene encoding the G protein alpha subunit. Although clinical manifestations may be heterogeneous, MAS is often characterized by the triad of fibrous dysplasia, café-au-lait skin pigmentations and hyperfunctioning endocrinopathy. We report here a 58-year old woman who presented for evaluation of hyperthyroidism, associated with nodular thyroid disease and elevated anti-TPO antibodies. She had been treated with a small dose of methimazole for 16 years but the remission of hyperthyroidism had not been attained. Neck ultrasound revealed a thyroid gland of normal volume with nodules in both lobes. The largest nodules (both hypervascularized and with microcalcifications) were evaluated by fine needle aspiration biopsy (FNAB) and were found to be benign. TSH-receptor antibodies (TRAb) were not elevated. The presence of anti-TPO antibodies led to a misdiagnosis of TRAb negative Graves’ disease. Over the course of her disease, and since childhood, the patient exhibited skeletal deformities and fragility fractures that were erroneously diagnosed as atypical osteogenesis imperfecta or familial expansile osteolysis. The presence of skin pigmentation on her right arm raised the suspicion of MAS. The GNAS activating mutation R201H was found in DNA derived from the thyroid nodule by FNAB. Furthermore, the R201H variant was also found in breast cancer tissue of the patient who had recently undergone right mastectomy. Hyperthyroidism is the second most common endocrinopathy in MAS after precocious puberty. The presumption of autoimmune thyroid disease and the incorrect skeletal diagnosis delayed the recognition of MAS in a patient with a classical combination of polyostotic fibrous dysplasia, hyperthyroidism and café-au-lait skin pigmentations. The GNAS genetic testing finally confirmed the diagnosis. Moreover, identification of the R201H mutation in the breast cancer specimen supports the oncogenic role of activating GNAS mutations in multiple tissues. Supported by MH CZ - DRO (Institute of Endocrinology - EÚ, 00023761) and AZV NU21-01-00448.