A case of McCune–Albright syndrome mimicking Paget’s disease of bone

Abstract

McCune–Albright syndrome is a genetic disorder characterized by polyostotic fibrous dysplasia, precocious puberty, and cafeau-lait spots. The main defect is a missense mutation in the GNAS1 gene, which results in the constitutive activation of the a-subunit of the Gs protein leading to overproduction of cAMP. Clinical presentation is variable due to the mosaic pattern of involvement of the tissues. Herein, we present a case of McCune–Albright syndrome (MAS) displaying the radiologic and biochemical features of Paget’s disease of bone. A 24-year-old woman was referred to our hospital due to skeletal deformities and facial dysmorphism. Her history included regular menses beginning at the age of 5 months, and bone deformities becoming evident at the age of about 5 years. Recently, she had been operated on due to a maxillary tumor; its pathological assessment yielded a diagnosis of fibrous dysplasia. On physical examination she was measured to be 90 cm in height. Facial asymmetry with depression of the left maxillary area was noted. She had extreme kyphoscoliosis and her right leg (tibia) had a bowing deformity. Routine blood chemistry showed a calcium level of 9.3 mg/dL, a phosphorus level in the lownormal range (2.9 mg/dL, normal 2.7–4.5), and a high alkaline phosphatase level (834 U/L, normal 42–98). Plasma levels of T3, T4, TSH, LH, FSH, estradiol, DHEAS-S, testosterone, free testosterone, growth hormone, prolactin, cortisol, and ACTH were all in the normal range. The parathyroid hormone level was 59.5 pg/mL (normal 9–55). Urinary hydroxyproline excretion was 392.3 mmol/mL creatinine (normal ,30). Radiological examination of the cranium revealed diffuse sclerosis of the skull base, thickening of the calvarium, and radiolucent areas (Figure 1). These changes were thought to be most compatible with Paget’s disease of bone. Both femurs showed widening of the bone shaft, ground glass appearance, and cortical thinning. Whole-body scintigram revealed dense uptake of the radiolabel in an asymmetric pattern (Figure 2). MRI scan of the sella revealed no pituitary adenoma. The presence of pathologically confirmed polyostotic fibrous dysplasia and a history of precocious puberty was considered decisive for diagnosis of MAS. The absence of cafe-au-lait spots does not exclude such a diagnosis, considering the mosaic nature of the disease. The most striking feature of the case was radiological findings closely mimicking those of Paget’s disease of bone. In the cranial radiographs, calvarial thickening, radiolucent areas resembling osteoporosis circumscripta, and sclerotic changes were considered compatible with Paget’s disease. Although these two disorders can cause thickening of the bones, X-ray findings of polyostotic fibrous dysplasia mimicking those of Paget’s disease have been emphasized very infrequently. Coexistence of both clinical situations has also been reported. Histologically, prominent osteoblasts on the surface of bone trabeculae and abnormal lamellar bone are characteristics of Paget’s disease and distinguish it from fibrous dysplasia. However, differentiating between Paget’s disease and polyostotic fibrous dysplasia should not be difficult on clinical grounds considering the very early onset of symptoms in the latter, particularly in the present case where the bony deformities had become evident at the age of about 5 years, which has not been seen in Paget’s disease. The high urinary hydroxyproline excretion and high serum alkaline phosphatase observed in our case may reflect the high bone turnover associated with polyostotic fibrous dysplasia, a feature also shared by Paget’s disease of bone. These findings suggest Address for correspondence and reprints: Dr. Sukru Palanduz, Fevzi Pasa Caddesi, Testereci Sokak, 1/10, Karagumruk, Fatih, 34230 Istanbul, Turkey. Figure 1. Lateral radiograph of the cranium showing calvarial thickening, radiolucent areas resembling osteoporosis circumscripta, and striking osteosclerosis involving particularly the skull base. Bone Vol. 24, No. 2 February 1999:157–158