Camurati-Engelmann Disease in Conjunction with Hypogonadism

ObjectiveTo report a case of Camurati-Engelmann disease (CED) in conjunction with hypogonadism, an association that has not been previously described.MethodsWe present the clinical, laboratory, and histopathologic features of our case. In addition, we review the molecular genetics of CED.ResultsCED is a rare autosomal dominant disorder of the skeleton, characterized by bilaterally symmetric, progressive dysplasia of the bones. The typical features of this disorder are hyperostotic and sclerotic changes in the bones, primarily of the extremities. Our patient, a 49-year-old male resident of a nursing home, presented with muscle weakness, waddling gait, bone pain, and increased fatigability, usual features of CED (which had been formally diagnosed when he was 8 years old). He also had hyponatremia, hyperkalemia, and almost undetectable serum testosterone. The gene responsible for CED has been mapped to the same locus as the gene for the synthesis of transforming growth factor (TGF-β1). Mutations in the TGFβ31 gene have been identified in patients with CED. TGF-β1 also has an important role in reproductive function, both during embryogenesis and in adulthood. It has predominant effects on steroidogenesis as well as spermatogenesis. We discuss the hormonal and histopathologic changes in our patient and postulate that the association of CED with hypogonadism could be attributable to the impaired regulation of gonadal growth and steroidogenesis, in which TGF-β1 has an important role.ConclusionWe propose that the association of CED with hypogonadism could be explained on the basis of a common underlying mutation in the TGFβ31 gene, leading to accumulation of excessive TGF-β1. (Endocr Pract. 2005;11:399-407)