GNAS mutated thyroid carcinoma in a patient with Mc Cune Albright syndrome

Mc Cune-Albright syndrome (MAS) is a rare disorder defined by the triad of polyostotic fibrous dysplasia, “café au lait” skin hyperpigmentation and hyperfunctioning endocrinopathies, such as precocious puberty. MAS is caused by an activating post zygotic somatic mutation of GNAS gene, coding for the alpha-subunit of the stimulatory G protein (Gsalpha). In endocrine tissues, this mutation results in overproduction of hormones and endocrine cell hyperfunction and proliferation. Whereas the association of hyperthyroidism and thyroid adenomas is well known in MAS, the relation with thyroid carcinoma has rarely been observed. We report the occurrence of a thyroid carcinoma in an 18-years old woman with MAS, revealed by subclinical hyperthyroidism detected during her systematic annual follow-up. Ultrasound and thyroid scintigraphy revealed the presence of a nodule in the right lobe. Pathology on hemithyroidectomy revealed an unexpected thyroid follicular carcinoma. Neoplastic thyroid cells harbored the GNAS R201C activating mutation. This observation suggests that MAS may predispose patients to thyroid carcinomas and supports the importance of thyroid assessment by physical examination, hormonal blood test and ultrasound, in the follow-up of patients with MAS. Because ultrasound diagnostic is challenging in MAS, needle puncture of palpable nodules should be advised.