Cortical and trabecular bone microarchitecture and turnover in alcohol-induced chronic pancreatitis: a histomorphometric study.

Alcohol-induced chronic pancreatitis is associated with bone loss, but bone histomorphometric data describing the mechanism of cortical (Ct) and trabecular (Tb) bone loss are scarce. In this case-control study, we investigated 13 black male patients aged 41.2 +/- 8.9 years with alcohol-induced chronic pancreatitis by routine iliac crest cortical and trabecular histomorphometry and by biochemistry relevant to bone, liver function, and iron overload. Patients showed lower values for Ct thickness (P = 0.018), endocortical (Ec) wall thickness (P = 0.0002), Tb bone volume (0.019), Tb thickness (0.001), Tb wall thickness (P < 0.0001), Ec osteoid thickness (P = 0.001), Ec mineral apposition rate (P = 0.011), and Ec bone formation rate (P = 0.035). Ec eroded surface (P = 0.004) was elevated compared to controls. Tb osteoid thickness (P = 0.14) and Tb mineral apposition rate (P = 0.195) tended to be lower than in controls. Levels of 25-hydroxyvitamin D (P < 0.005), serum magnesium (P = 0.02), and ascorbic acid (P = 0.049) were lower and urine calcium/creatinine ratios higher than in controls. Alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) were negatively correlated but iron markers were positively correlated with bone structural and formation variables. The histomorphometric data were found to be consistent with alcohol bone disease. Osteomalacia was not a feature. Secondary pathogenetic factors were liver disease, hypovitaminosis D and C, diabetes mellitus, and possibly chronic pancreatitis.

Complete androgen insensitivity syndrome in a black South African family: a clinical and molecular investigation.

OBJECTIVE: To present the first report of a clinical and molecular investigation of a black South African family with complete androgen insensitivity syndrome (CAIS). METHODS: Biochemical and chromosomal analyses were performed. In addition, the molecular study included microsatellite analysis and DNA sequencing. RESULTS: The index case, an unmarried 21-year-old black phenotypic female patient with primary amenorrhea, was identified in the Division of Endocrinology at a tertiary hospital affiliated with the University of the Witwatersrand. A detailed family history identified further potentially affected members (on the basis of primary amenorrhea), who were also included in the study. A total of 13 family members, including 6 affected subjects, were involved in the molecular study. All affected persons had a 46,XY karyotype, female phenotype, and hormonal profiles commensurate with their clinical diagnosis. The androgen receptor gene in an affected patient was examined for mutations by DNA sequencing. Mutation screening was extended to other family members. The genetic basis for CAIS in this large family is the missense mutation, D732Y, in exon 5 of the androgen receptor ligand-binding domain. CONCLUSION: To our knowledge, this is the first case report of CAIS in South Africa in which molecular genetic techniques were used to substantiate the clinical diagnosis. The findings in this study have implications for genetic counseling in this family.