McCune-Albright syndrome: a case of an adult with fibrous dysplasia, severe cardiopulmonary complications, acromegaly, and chronic myeloid leukemia.

Abstract

McCune-Albright syndrome (MAS) is a rare mosaic disorder characterized by the classic triad of fibrous dysplasia of bone (FD), café-au-lait skin macules, and hyperfunctioning endocrinopathies. MAS is caused by a postzygotic mutation in the G-protein alpha subunit (GNAS) gene resulting in G-protein α-subunit somatic activation. There is no approved treatment for MAS. We present the case of a 43-yr-old male carpenter with severe polyostotic FD and adult-onset growth hormone (GH) excess who was treated with denosumab and somatostatin analog, complicated with a diagnosis of chronic myeloid leukemia (CML). The patient had multiple skeletal lesions, resulting in pain on movement and neurovascular compromise of the left arm. A forequarter amputation was considered to treat a large clavicular lesion, however, involvement of his thoracic cage resulted in significant cardiopulmonary impairment, including restrictive lung disease, and the surgery was deemed too risky. Denosumab was commenced after failed intravenous bisphosphonate for pain management, resulting in alleviation of pain. Screening of endocrinopathy revealed GH excess with an elevated Insulin-like Growth Factor-1 (IGF-1) level and 7 mm pituitary adenoma. Lanreotide was commenced as a medical therapy, resulting in a reduction in IGF-1 levels. Over 9 mo into the denosumab treatment, the patient was diagnosed with CML in the context of routine full blood examination. The patient achieved a hematological remission with imatinib. Polyostotic FD can lead to serious complications from deformities of the skeleton, including cardiopulmonary complications. This case represents a patient with a severe spectrum of MAS/FD with a diagnosis of CML. We postulate that CML is unlikely due to the MAS, as the two have different pathogenic pathways. Denosumab is effective in pain management, however, it should be used with caution, and there are no large studies to guide long-term management. Evaluation and management of MAS should also include detailed endocrinopathy assessment and screening, even in adulthood.