Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.

Diabetes vaccines: a future to be realized.

Immune-mediated (type 1) diabetes mellitus (IMD) is an autoimmune disease resulting from the chronic destruction of pancreatic islet cells by autoreactive T lymphocytes. Although there has been much advancement in diabetes management, targeting the precise etiology of the disease process has remained elusive. Recent progress in the understanding of the immunopathogenesis of IMD, however, has led to new intervention strategies, especially antigen-based therapies given as altered peptide ligands (APLs) or as vaccines. Instead of using immunosuppressive agents to suppress an already dysfunctional immune system, antigen specific vaccines or even non-antigen specific immunostimulants present a unique opportunity to boost regulatory function and thereby regain tolerance to self. We discuss here the pathogenesis of IMD as it relates to therapeutic possibilities, review various intervention strategies that have been successful in rodent models, and then present recent progress in human trials of diabetes intervention and prevention through vaccine prototypes.